NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®)

Testicular Cancer
Version 2.2024 — October 29, 2024

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Testicular Cancer Discussion

*Timothy Gilligan, MD, MS/Chair † Peter Humphrey, MD, PhD ≠ Sumit Shah, MD, MPH ‡
Case Comprehensive Cancer Center/ Yale Cancer Center/Smilow Cancer Hospital Stanford Cancer Institute
University Hospitals Seidman Cancer Ellis G. Levine, MD † Nirmish Singla, MD, MSc ω
Center and Cleveland Clinic Taussig Roswell Park Comprehensive Cancer Center The Sidney Kimmel Comprehensive
Cancer Institute Cancer Center at Johns Hopkins
Amy Luckenbaugh, MD ω
*Daniel W. Lin, MD/Vice-Chair ω Vanderbilt-Ingram Cancer Center Kanishka Sircar, MD ≠
Fred Hutchinson Cancer Center The University of Texas
Benjamin Maughan, MD, PharmD †
Nabil Adra, MD, MSc † Huntsman Cancer Institute MD Anderson Cancer Center
Indiana University Melvin and Bren Simon at the University of Utah Benjamin A. Teply, MD †
Comprehensive Cancer Center Fred & Pamela Buffett Cancer Center
Bradley McGregor, MD †
*Rahul Aggarwal, MD † ‡ Þ Dana-Farber/Brigham and David VanderWeele, MD, PhD †
UCSF Helen Diller Family Women's Cancer Center Robert H. Lurie Comprehensive Cancer
Comprehensive Cancer Center Center of Northwestern University
Paul Monk, MD †
Aditya Bagrodia, MD ω The Ohio State University Comprehensive David Vaughn, MD †
UC San Diego Moores Cancer Center Cancer Center - James Cancer Hospital Abramson Cancer Center
Daniel Costa, MD ∩ and Solove Research Institute at the University of Pennsylvania
UT Southwestern Simmons *Joel Picus, MD ‡ Kosj Yamoah, MD, PhD §
Comprehensive Cancer Center Siteman Cancer Center at Barnes- Moffitt Cancer Center
Alexandra Drakaki, MD, PhD † Jewish Hospital and Washington Ali Zhumkhawala, MD ω
UCLA Jonsson Comprehensive Cancer Center University School of Medicine City of Hope National Medical Center
Hamid Emamekhoo, MD † Soroush Rais-Bahrami, MD ω
University of Wisconsin O'Neal Comprehensive
Carbone Cancer Center Cancer Center at UAB
Christopher Evans, MD ω Zachery Reichert, MD, PhD † Þ
UC Davis Comprehensive Cancer Center University of Michigan
Rogel Cancer Center NCCN
Darren R. Feldman, MD † Sarah Montgomery, BA
Memorial Sloan Kettering Cancer Center Jean-Claude Rwigema, MD § Rashmi Kumar, PhD
*Daniel M. Geynisman, MD † Mayo Clinic Comprehensive Cancer Center Bailee Sliker, PhD
Fox Chase Cancer Center Philip Saylor, MD †
Mass General Cancer Center
Laura Graham, MD †
University of Colorado Cancer Center Ankeet Shah, MD † ω
Duke Cancer Institute ‡ Hematology/Hematology oncology
Þ Internal medicine
† Medical oncology
≠ Pathology
Continue ∩ Radiology/Diagnostic radiology
NCCN Guidelines Panel Disclosures § Radiotherapy/Radiation oncology
ω Urology
* Discussion writing committee member

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Table of Contents
Testicular Cancer Discussion

NCCN Testicular Cancer Panel Members

Summary of the Guidelines Updates Clinical Trials: NCCN believes that
the best management for any patient
Workup, Primary Treatment, and Pathologic Diagnosis (TEST-1) with cancer is in a clinical trial.
Pure Seminoma: Postdiagnostic Workup and Clinical Stage (SEM-1) Participation in clinical trials is
• Stage IA, IB, and IS (SEM-2)
• Stage IIA, IIB, IIC, and III (SEM-3)
especially encouraged.
• Post First-Line Chemotherapy Management (SEM-4) Find an NCCN Member Institution:
• Recurrence and Second-Line Therapy (SEM-5) https://www.nccn.org/home/member-
• Post Second-Line Therapy Management (SEM-6) institutions.
• Third-Line Therapy (SEM-7)
Nonseminoma: Postdiagnostic Workup and Clinical Stage (NSEM-1) NCCN Categories of Evidence and
• Stage I with and without Risk Factors, Stage IS (NSEM-2) Consensus: All recommendations
• Stage IIA, IIB (NSEM-3) are category 2A unless otherwise
• Post First-Line Chemotherapy Management (NSEM-4) indicated.
• Postsurgical Management (NSEM-5)
• Stage IS, IIA S1, IIB S1, IIC, IIIA, IIIB, IIIC, and Brain Metastases (NSEM-6) See NCCN Categories of Evidence
• Postchemotherapy Management of Partial Response to Primary Treatment (NSEM-7) and Consensus.
• Recurrence and Second-Line Therapy (NSEM-8) NCCN Categories of Preference:
• Post Second-Line Therapy Management (NSEM-9) All recommendations are considered
• Third-Line Therapy (NSEM-10)
Follow-up for Seminoma (TEST-A)
appropriate.
Follow-up for Nonseminoma (TEST-B) See NCCN Categories of Preference.
Principles of Radiotherapy for Pure Testicular Seminoma (TEST-C)
Risk Classification for Advanced Disease (TEST-D)
First-Line Chemotherapy Regimens for Germ Cell Tumors (TEST-E)
Second-Line Chemotherapy Regimens for Metastatic Germ Cell Tumors (TEST-F)
Third-Line Chemotherapy Regimens for Metastatic Germ Cell Tumors (TEST-G)
Principles of Surgery for Germ Cell Tumors (TEST-H)
Principles of Imaging (TEST-I)
Staging (ST-1)
Abbreviations (ABBR-1)

The NCCN Guidelines® are a statement of evidence and consensus of the authors regarding their views of currently accepted approaches to
treatment. Any clinician seeking to apply or consult the NCCN Guidelines is expected to use independent medical judgment in the context of individual
clinical circumstances to determine any patient’s care or treatment. The National Comprehensive Cancer Network® (NCCN®) makes no representations
or warranties of any kind regarding their content, use or application and disclaims any responsibility for their application or use in any way. The NCCN
Guidelines are copyrighted by National Comprehensive Cancer Network®. All rights reserved. The NCCN Guidelines and the illustrations herein may
not be reproduced in any form without the express written permission of NCCN. ©2024.
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NCCN Guidelines Version 2.2024 NCCN Guidelines Index

Table of Contents
Testicular Cancer Discussion

Updates in Version 2.2024 of the NCCN Guidelines for Testicular Cancer from Version 1.2024 include:
MS-1
• The discussion section has been updated to reflect the changes in the algorithm.

Updates in Version 1.2024 of the NCCN Guidelines for Testicular Cancer from Version 1.2023 include:
Global Changes
• References updated throughout the guidelines.
• CT and MRI contrast recommendations updated throughout the guidelines.
• Use of "salvage" replaced throughout the guidelines.
TEST-1
• Primary treatment, Radical inguinal orchiectomy
Footnote d applied: Although rare, when a patient presents with rapidly increasing beta-hCG or AFP and symptoms related to disseminated disease with a
testicular mass, chemotherapy can be initiated immediately without waiting for a biopsy diagnosis or performing orchiectomy. However, orchiectomy should be
performed at completion of chemotherapy.
SEM-1
• Footnote i modified: For select cases of clinical stage IIA disease with borderline retroperitoneal lymph nodes, waiting 4–6 4 weeks and repeating
imaging (CT or MRI chest/abdomen/pelvis with contrast) to confirm staging before initiating treatment can be considered. (Also for SEM-3, and footnote
n on NSEM-3)
SEM-2
• Stage IS, follow-up option modified: Repeat elevated serum tumor marker measurement and assess with imaging: Chest/abdomen/pelvis CT (with
contrast) to scan for evaluable disease.
• Footnote k revised: Recommend abdomen/pelvis CT scan and chest x-ray or CT scan imaging within the 4 weeks prior to the initiation of chemotherapy
to confirm staging, even if the scan was done previously. (Also for footnote m on NSEM-2)
SEM-3
• Stage IIA, primary treatment option added: Nerve-sparing RPLND
Follow-up added: See Follow-up for Seminoma, Table 3
• Footnote s added: Providers should engage in shared decision-making for Stage IIA seminoma that includes informing patients of the recurrence rates
and potential for dual-therapy with each treatment option.
• Footnote x added: RPLND is recommended within 4 weeks of CT scan and within 7–10 days of confirmation of normal tumor markers.
• Footnote y added: See Principles of Surgery for Germ Cell Tumors.
• Footnote z added: Recommend referral to a high-volume center.
• Footnote aa added: For nonbulky IIB, ≤3 cm in transaxial long axis.
SEM-4
• Positive for viable seminoma, follow-up option modified: Incomplete resection or positive biopsy
• Footnote dd added: Consider referral to a high-volume center. Assessment of resectability should be performed.

Continued
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Testicular Cancer Discussion

Updates in Version 1.2024 of the NCCN Guidelines for Testicular Cancer from Version 1.2023 include:
SEM-5
• Footnote hh modified: To assess response after treatment, CT with contrast or MRI with and without contrast of chest/abdomen/pelvis and any other
sites of disease is recommended. FDG-PET from skull base to mid thigh may also be considered in assessing treatment response and residual
masses following chemotherapy in patients with seminoma. (Also for SEM-6, SEM-7)
SEM-7
• Prior first- and second-line conventional dose chemotherapy
Third-line therapy option added: Microsatellite instability/mismatch repair (MSI/MMR) or tumor mutational burden (TMB) testing if progression after
high-dose chemotherapy or third-line therapy
• Prior high-dose chemotherapy
Third-line therapy option added: MSI/MMR or TMB testing if progression after high-dose chemotherapy or third-line therapy
• Footnote removed: Microsatellite instability/mismatch repair (MSI/MMR) or tumor mutational burden (TMB) testing if progression after high-dose
chemotherapy or third-line therapy.
NSEM-1
• Footnote c modified: CT with contrast and MRI with and without contrast. (Also for NSEM-4)
• Footnote removed: With and without contrast.
NSEM-4
• Post first-line chemotherapy management
Residual embryonal, yolk sac, choriocarcinoma, or seminoma element
◊ Option modified: Chemotherapy (preferred) for 2 cycles (EP or TIP or VIP or VeIP)
◊ Option added: Surveillance for select patients
• Footnote u added: Surveillance is a reasonable alternative to chemotherapy for patients with residual masses that have been completely resected if
all of the residual masses have less than 10% viable cancer cells in the resected tissue.
NSEM-5
• pN2, option modified: Chemotherapy (preferred): EP for 2 cycles
• pN3; option modified: Chemotherapy preferred: BEP for 3 cycles or EP for 4 cycles
• pN3, option added: Surveillance
NSEM-6
• Footnote x modified: To assess response after treatment, MRI with and without contrast or CT with contrast of chest/abdomen/pelvis and any other
sites of disease is recommended. FDG-PET has no role in assessing treatment response and residual masses following chemotherapy in patients
with nonseminoma. (Also for NSEM-8, NSEM-9, and NSEM-10)
TEST-A (1 of 3)
• Footnote f added: With and without contrast (Also for TEST-A 2, TEST-A 3, and footnote e on TEST-B 1, TEST-B 2, and TEST-B 3)
TEST-A (2 of 3)
• Surveillance Table 4 added for Clinical Stage IIA Seminoma: Post-Primary RPLND and NOT Treated with Adjuvant Chemotherapy
Recurrence column added: If Recurrence, treat according to extent of disease at relapse

Note: All recommendations are category 2A unless otherwise indicated.

Clinical Trials: NCCN believes that the best management of any patient with cancer is in a clinical trial. Participation in clinical trials is especially encouraged.
Continued
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Table of Contents
Testicular Cancer Discussion

Updates in Version 1.2024 of the NCCN Guidelines for Testicular Cancer from Version 1.2023 include:
TEST-A (3 of 3)
• Surveillance Table 5 added for Clinical Stage IIA Seminoma: Post-Primary RPLND and Treated with Adjuvant Chemotherapy
Recurrence column added: If Recurrence, treat according to extent of disease at relapse
• Footnote k modified: Patients with FDG-PET-negative residual mass measuring >3 cm following chemotherapy should undergo an MRI with and
without contrast or abdomen/pelvis CT scan with contrast every 6 months for the first year, then annually for 5 years.
TEST-B (1 of 3)
• Table 6
Chest x-ray, months 3 and 4 surveillance recommendations modified: Annually As clinically indicated
TEST-F
• High-Dose Chemotherapy Regimens
Preferred regimen clarified:
◊ Carboplatin 700 mg/m2/day (body surface area) IV administered on days -5, -4, -3
◊ Etoposide 750 mg/m2/day IV administered on days -5, -4, -3
◊ Administer days -5, -4, and -3 days before peripheral blood stem cell infusion for 2 cycles
TEST-G (1 of 3)
• Preferred Regimens (High-Dose Chemotherapy)
• Carboplatin/etoposide regimen clarified:
Carboplatin 700 mg/m2/day (body surface area) IV administered on days -5, -4, -3
 Etoposide 750 mg/m2/day IV administered on days -5, -4, -3
Administered days -5, -4, and -3 days before peripheral blood stem cell infusion for 2 cycles
TEST-H (1 of 2)
• Principles of Surgery for Germ Cell Tumors
Bullet 1, sub-bullet 1 added: When a patient presents with a testicular mass, rapidly increasing beta-hCG or AFP, metastatic disease on imaging, and
symptoms related to disseminated disease, chemotherapy can be initiated immediately without waiting for orchiectomy or a biopsy-proven histologic
diagnosis. However, radical inguinal orchiectomy should be performed at completion of chemotherapy.
Bullet 2 modified: A template dissection or a nerve-sparing Nerve-sparing and/or template dissection approach to minimize the risk of ejaculatory
disorders should be considered in patients undergoing primary RPLND for stage I nonseminoma.
• Testis-Sparing Surgery (TSS)
Indications for TSS
◊ Bullet 1 modified: Synchronous bilateral germ cell tumors, a solitary testicle with a mass suspicious for germ cell tumor, or a functionally solitary
testicle with adequate gonadal function with respect to androgen production or sperm production (eg, history of contralateral testicular atrophy).
◊ Bullet removed: Non-palpable testicular masses <2 cm are associated with benign tumors in up to 80% of patients, and therefore, TSS may be
considered in these patients in whom TSS is technically feasible.

Note: All recommendations are category 2A unless otherwise indicated.

Clinical Trials: NCCN believes that the best management of any patient with cancer is in a clinical trial. Participation in clinical trials is especially encouraged.
Continued
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Table of Contents
Testicular Cancer Discussion

Updates in Version 1.2024 of the NCCN Guidelines for Testicular Cancer from Version 1.2023 include:
TEST-H (2 of 2)
• Principles of Surgery for Germ Cell Tumors
Section added: Retroperitoneal Lymph Node Dissection (RPLND)
◊ Bullet added: A template dissection or a nerve-sparing approach to minimize the risk of ejaculatory disorders should be considered in patients
undergoing primary RPLND for stage I nonseminoma.
◊ Bullet added: The “split and roll” technique in which lumbar vessels are identified and sequentially ligated allows resection of all lymphatic tissue
around and behind the great vessels (ie, aorta, IVC) and minimizes the risk of an in-field recurrence.
◊ Bullet added: Referral to high-volume centers should be considered for RPLND.
◊ Bullet added: Minimally invasive laparoscopic or robotic approaches to RPLND have limited long-term data and relatively high adjuvant
chemotherapy use. Therefore, minimally invasive RPLND is not recommended as standard management, but can be considered in highly selected
cases at high-volume centers.
Postchemotherapy Setting
◊ Bullet added: Completeness of resection is a consistent independent predictor of clinical outcome. In postchemotherapy RPLND, surgical margins
should not be compromised in an attempt to preserve ejaculation. Additional procedures and resection of adjacent structures may be required.
◊ Bullet removed: Referral to high-volume centers should be considered for surgical resection of masses postchemotherapy.
◊ Bullet removed: Limited data suggest increased frequency of aberrant recurrences with the use of minimally invasive laparoscopic or robotic
approaches to RPLND. Therefore, minimally invasive RPLND is not recommended as standard management, but can be considered in highly
selected cases at high-volume centers.
TEST-I
• Principles of Imaging
Staging
◊ Pure Seminoma and Nonseminoma, bullet 1 modified: Abdomen/pelvis CT scan with contrast and chest x-ray or CT scan or abdomen/pelvis MRI
with and without contrast is recommended within 4 weeks prior to the initiation of chemotherapy, RPLND, or RT to confirm staging, even if scan
was performed previously.
Surveillance
◊ Pure Seminoma and Nonseminoma, bullet 1 modified: MRI with and without contrast can be considered in select circumstances in place of an
abdomen/pelvis CT.

Note: All recommendations are category 2A unless otherwise indicated.

Clinical Trials: NCCN believes that the best management of any patient with cancer is in a clinical trial. Participation in clinical trials is especially encouraged.

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Testicular Cancer Discussion

WORKUP PRIMARY TREATMENTd PATHOLOGIC DIAGNOSIS

Postdiagnostic
Pure seminoma (pure
Workup and
seminoma histology and AFP
Clinical Stage
• Consider abdomen/pelvis CT with normal; may have elevated
• H&P (SEM-1)
contrast or MRI with and without beta-hCG)a
• Alpha-fetoprotein (AFP)a
contrast
• beta-human chorionic
• Radical inguinal orchiectomyd,e
Suspicious gonadotropin (hCG)a,b
• Discuss sperm banking, if
testicular • Lactate dehydrogenase Nonseminomatous germ
clinically indicatedf Postdiagnostic
mass (LDH) cell tumor (NSGCT)
• Discuss testicular prosthesis Workup and
• Chemistry profilec (includes mixed seminoma/
• For patients with bilateral Clinical Stage
• Testicular ultrasound nonseminoma tumors and
testicular abnormalities, consider (NSEM-1)
inguinal biopsyg of contralateral seminoma histology with
testish elevated AFP)a

a Mildly elevated, non-rising AFP levels may not indicate presence of germ cell tumor.
Decisions to treat should not be based on AFP values <20 ng/mL. More highly elevated e May consider testis-sparing surgery (ie, partial orchiectomy) in select
AFP levels generally indicate the presence of nonseminomatous tumor elements. patients. See Principles of Surgery (TEST-H).
Further workup should be considered before initiating treatment for mildly elevated beta- f For patients wishing to preserve fertility, sperm banking is recommended
hCG (generally <20 IU/L) since other factors, including hypogonadism and marijuana prior to chemotherapy, radiation therapy, or retroperitoneal lymph node
use, can cause false-positive results. See Discussion. dissection (RPLND). For patients with a single testicle and patients
b Quantitative analysis of beta subunit. undergoing bilateral orchiectomy, sperm banking is recommended prior to
c Consider measuring baseline levels of gonadal function. orchiectomy.
d Although rare, when a patient presents with rapidly increasing beta-hCG or AFP and g Inguinal exploration with exposure of testis, with direct observation and
symptoms related to disseminated disease with a testicular mass, chemotherapy can be partial orchiectomy. See Principles of Surgery (TEST-H).
initiated immediately without waiting for a biopsy diagnosis or performing orchiectomy. h If ultrasound shows cryptorchid testis, marked atrophy, or suspicious mass.
However, orchiectomy should be performed at completion of chemotherapy. Biopsies are not recommended for microcalcifications.

Note: All recommendations are category 2A unless otherwise indicated.

Clinical Trials: NCCN believes that the best management of any patient with cancer is in a clinical trial. Participation in clinical trials is especially encouraged.

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TEST-1
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Testicular Cancer - Pure Seminoma Discussion

PATHOLOGIC DIAGNOSIS POSTDIAGNOSTIC WORKUP CLINICAL STAGE

AJCC TNM Staging Classification

Stage
IA, IBg
Primary Treatment and
• Abdomen/pelvis CTc or MRId Follow-up (SEM-2)
• Chest x-ray Stage ISh
• Chest CT if:
Pure seminomaa Positive abdomen CT or
(pure seminoma histology abnormal chest x-ray
and AFP normal; may have • Repeat beta-hCG, LDH, and AFP because
elevated beta-hCGb) staging is based on post-orchiectomy
valuesb,e Stage
• Brain MRI,d if clinically indicatedf IIA,i IIB
• Recommend sperm banking, if clinically Primary Treatment and
indicated Follow-up (SEM-3)
Stage
IIC, IIIg
a Mediastinal primary seminoma should be treated by risk status used for gonadal
seminomas with etoposide/cisplatin for 4 cycles or bleomycin/etoposide/cisplatin for 3
cycles.
b Mildly elevated, non-rising AFP levels may not indicate presence of germ cell tumor.
Decisions to treat should not be based on AFP values <20 ng/mL. More highly elevated
AFP levels generally indicate the presence of nonseminomatous tumor elements. Further
workup should be considered before initiating treatment for mildly elevated beta-hCG
(generally <20 IU/L) since other factors, including hypogonadism and marijuana use, can
cause false-positive results. See Discussion.
c Unless performed prior to orchiectomy. f Eg, beta-hCG >5000 IU/L, non-pulmonary visceral metastases,
d CT with contrast or MRI with and without contrast. extensive lung metastasis, or neurologic symptoms present.
e Elevations of AFP either pre- or post-orchiectomy indicate the presence of g The panel recommends staging tumors with discontinuous invasion of
nonseminomatous elements. For patients with elevated pre-orchiectomy beta-hCG levels, the spermatic cord as pT3 (high-risk stage I) and not as M1 (stage III) as
beta-hCG levels should be followed with repeated determinations after orchiectomy to is recommended in the 8th edition of the AJCC Cancer Staging Manual.
determine their trajectory and, if declining, their nadir. The expected half-life for beta- If surveillance is elected, the pelvis should be included in the imaging
hCG is 3 days or less. For patients with normal imaging (ie, stage I), rising or persistently due to a higher risk of pelvic relapses in these patients. See Discussion.
elevated beta-hCG levels generally indicate the presence of metastatic disease (stage h For further information on stage IS, see Discussion.
IS). For patients with metastatic disease to the retroperitoneum or beyond (stage II or III), i For select cases of clinical stage IIA disease with borderline
highly elevated post-orchiectomy beta-hCG (>1000 IU/L) levels may indicate the presence retroperitoneal lymph nodes, waiting 4 weeks and repeating imaging (CT
of nonseminomatous tumor elements. See Discussion. or MRI) to confirm staging before initiating treatment can be considered.

Note: All recommendations are category 2A unless otherwise indicated.

Clinical Trials: NCCN believes that the best management of any patient with cancer is in a clinical trial. Participation in clinical trials is especially encouraged.

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SEM-1
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Testicular Cancer - Pure Seminoma Discussion

CLINICAL PRIMARY TREATMENTj FOLLOW-UP RECURRENCE

STAGE
Surveillance for pT1–pT3 tumors
See Follow-up for Seminoma, Table 1 (TEST-A 1 of 2)
(strongly preferred)

or

Stage Single-agent carboplatink,l

IA, IB (area under the curve [AUC] = 7 x 1 See Follow-up for Seminoma, Table 2 (TEST-A 1 of 2) For recurrence,
cycle or AUC = 7 x 2 cycles) treat according to
extent of disease at
or relapsep,q

Radiation therapy (RT)m See Follow-up for Seminoma, Table 2 (TEST-A 1 of 2)

(20 Gy or 25.5 Gy)n
Repeat elevated serum tumor marker
Stage measurementb and assess with imagingk:
ISh • Chest/abdomen/pelvis CT (with contrast) to
scan for evaluable diseaseh,o

b Mildly elevated, non-rising AFP levels may not indicate presence of germ cell
tumor. Decisions to treat should not be based on AFP values <20 ng/mL. More
highly elevated AFP levels generally indicate the presence of nonseminomatous
tumor elements. Further workup should be considered before initiating treatment
for mildly elevated beta-hCG (generally <20 IU/L) since other factors, including
hypogonadism and marijuana use, can cause false-positive results. See m Principles of Radiotherapy for Pure Testicular Seminoma (TEST-C).
Discussion. n For stage I seminoma, long-term follow-up studies indicate an increase in late
h For further information on stage IS, see Discussion.
j Discuss sperm banking prior to chemotherapy or radiation treatment. toxicities with radiation treatment. See Discussion.
o Elevated tumor markers increase the risk of disease outside of the
k Recommend imaging within the 4 weeks prior to the initiation of chemotherapy to
retroperitoneum. Therefore, systemic therapy should be encouraged.
confirm staging, even if the scan was done previously. See Principles of Imaging See First-Line Chemotherapy Regimens for Germ Cell Tumors (TEST-E).
(TEST-I). p Patients should not be treated based upon an elevated LDH alone.
l There are limited long-term follow-up data on the toxicity and efficacy of q Patients previously on surveillance can be treated with RT or chemotherapy
carboplatin. A recent population-based study suggested patients with larger (depending on the extent of disease). Patients who received carboplatin or RT
tumors, rete testis involvement, or both derive a smaller reduction in relapse rate should be treated with first-line cisplatin-based chemotherapy. See First-Line
with 1 cycle of carboplatin than previously reported. See Discussion. Chemotherapy Regimens for Germ Cell Tumors (TEST-E).

Note: All recommendations are category 2A unless otherwise indicated.

Clinical Trials: NCCN believes that the best management of any patient with cancer is in a clinical trial. Participation in clinical trials is especially encouraged.

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SEM-2
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Testicular Cancer - Pure Seminoma Discussion

CLINICAL PRIMARY TREATMENTj FOLLOW-UP RECURRENCE

STAGEr RT to include para-aortic and ipsilateral See Follow-up for Seminoma, For recurrence, treat
iliac lymph nodes to a dose of 30 Gym Table 3 (TEST-A 2 of 2) according to extent of
Stage or disease at relapsep
IIAi,s Post First-Line Chemotherapy
First-Line chemotherapyv:
BEPw for 3 cycles or EP for 4 cycles Management and Follow-up (SEM-4)
or See Follow-up for Seminoma,
Nerve-sparing RPLNDx,y,z
Table 3 (TEST-A 2 of 2)

First-Line chemotherapyv: Post First-Line Chemotherapy

BEPw for 3 cycles or EP for 4 cycles Management and Follow-up (SEM-4)
Stage or
IIB RT in select non-bulky (≤3 cm)aa cases For recurrence, treat
to include para-aortic and ipsilateral See Follow-up for Seminoma,
according to extent of
iliac lymph nodes to a dose of 36 Gym Table 3 (TEST-A 2 of 2)
disease at relapsep

First-Line chemotherapyv:
Good risku BEPw for 3 cycles (category 1)
or Post First-Line Preferred Regimens
Stage EP for 4 cycles (category 1) Chemotherapy BEP = Bleomycin/etoposide/cisplatin
IIC, IIIt Management EP = Etoposide/cisplatin
First-Line chemotherapyv: and Follow-up (SEM-4) Other Recommended Regimens
Intermediate BEPw for 4 cycles (category 1) VIP = Etoposide/ifosfamide/cisplatin
riskr,u or
VIP for 4 cycles t All stage IIC and stage III seminomas are considered good-risk disease except
i For select cases of clinical stage IIA disease with borderline retroperitoneal lymph nodes, waiting for stage III disease with non-pulmonary visceral metastases (eg, bone, liver,
4 weeks and repeating imaging (CT or MRI) to confirm staging before initiating treatment can be brain), which is considered intermediate risk.
considered. u Risk Classification for Advanced Disease (TEST-D).
j Discuss sperm banking prior to chemotherapy or radiation treatment. v First-Line Chemotherapy Regimens for Germ Cell Tumors (TEST-E).
m See Principles of Radiotherapy for Pure Testicular Seminoma (TEST-C). w Consider a bleomycin-free regimen in patients at increased risk for bleomycin
p Patients should not be treated based upon an elevated LDH alone.
r Intermediate risk in seminoma is based on metastases to organs other than the lungs (stage IIIC). toxicity, such as those with reduced glomerular filtration rate (GFR) or older age.
Stage IIIB does not apply to pure seminomas. Patients with elevated AFP have nonseminomas. In See Discussion.
x RPLND is recommended within 4 weeks of CT scan and within 7–10 days of
patients with a serum beta-hCG >1000 IU/L, consider the possibility of a nonseminoma, re-review
surgical specimen with pathology, and consider discussion with a high-volume center. LDH and beta- confirmation of normal tumor markers.
hCG alone should not be used to stage or risk stratify patients with pure seminoma. y Principles of Surgery for Germ Cell Tumors (TEST-H).
s Providers should engage in shared decision-making for Stage IIA seminoma that includes informing z Recommend referral to a high-volume center.
patients of the recurrence rates and potential for dual-therapy with each treatment option. aa For nonbulky IIB, ≤3 cm in transaxial long axis.

Note: All recommendations are category 2A unless otherwise indicated.

Clinical Trials: NCCN believes that the best management of any patient with cancer is in a clinical trial. Participation in clinical trials is especially encouraged.

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Testicular Cancer - Pure Seminoma Discussion

STAGE IIA, IIB, IIC, III AFTER FIRST LINE POST FIRST-LINE FOLLOW-UP RECURRENCE
TREATMENT WITH CHEMOTHERAPY CHEMOTHERAPY
MANAGEMENT
No residual mass or
residual mass See Follow-up For
≤3 cm and normal Surveillance for Seminoma, recurrence,
serum AFP and Table 3 see Second-Line
beta-hCG (TEST-A 2 of 2) Therapy (SEM-5)

Surveillance See Follow-up for

Negative Surveillance Seminoma, Table 4
or (TEST-A 2 of 2)
• Chest/ Residual
abdomen/ mass
(>3 cm) Consider Repeat FDG-PET/ Complete Consider 2
pelvis CT resection cycles adjuvant
and FDG-PET/CT Indeterminate CT or CT scan in 6–8
scanwd or chemotherapyee
MRI normal scan from skull weekscc Incomplete
base to mid- Positive resection
• Serum serum for viable
AFP and thigh (6 wks or Second-Line
tumor
or more post- seminomaff positive Therapy
markers beta-hCG Resection
chemotherapy) of residual biopsy (SEM-5)
Positivebb massdd or or
Biopsy Progression
Negative See Follow-up for
Progressive disease for viable Seminoma, Table 4
(growing mass or Second-Line Therapyee seminomaff (TEST-A 2 of 2)
rising markers)b (SEM-5)
Recurrence,
See Second-Line
b Mildlyelevated, non-rising AFP levels may not indicate presence of germ cell tumor. cc If still indeterminate, recommend following with CT Therapy (SEM-5)
Decisions to treat should not be based on AFP values <20 ng/mL. More highly scan or biopsy.
elevated AFP levels generally indicate the presence of nonseminomatous tumor dd Consider referral to a high-volume center.
elements. Further workup should be considered before initiating treatment for mildly Assessment of resectability should be performed.
elevated beta-hCG (generally <20 IU/L) since other factors, including hypogonadism ee EP or TIP or VIP or VeIP.
and marijuana use, can cause false-positive results. See Discussion. ff In rare cases, nonseminomatous elements will be
d CT with contrast or MRI with and without contrast. identified. If they are non-teratomatous, then proceed
bb Principles of Imaging (TEST-I). in the same fashion as for viable seminoma above.

Note: All recommendations are category 2A unless otherwise indicated.

Clinical Trials: NCCN believes that the best management of any patient with cancer is in a clinical trial. Participation in clinical trials is especially encouraged.

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RECURRENCEgg SECOND-LINE THERAPYhh,ii

• Clinical trial (preferred)

• Chemotherapyjj
Prior first-line Conventional-dose second-line chemotherapy Post Second-Line Therapy
chemotherapy (VeIP for 4 cycles or TIP for 4 cycles) Management (SEM-6)
High-dose chemotherapy
• Recommend sperm banking if clinically indicated

Preferred Regimens
• High-dose chemotherapyjj
• TIP = Paclitaxel/ifosfamide/cisplatin
• VeIP = Vinblastine/ifosfamide/cisplatin
gg It is preferred that patients with recurrent seminoma be treated at centers with expertise in the
management of this disease.
hh To assess response after treatment, CT with contrast or MRI with and without contrast of chest/
abdomen/pelvis and any other sites of disease is recommended. FDG-PET from skull base to mid
thigh may also be considered in assessing treatment response and residual masses following
chemotherapy in patients with seminoma.
ii Includes best supportive care and palliative care. See NCCN Guidelines for Palliative Care.
jj Second-Line Chemotherapy Regimens for Metastatic Germ Cell Tumors (TEST-F).

Note: All recommendations are category 2A unless otherwise indicated.

Clinical Trials: NCCN believes that the best management of any patient with cancer is in a clinical trial. Participation in clinical trials is especially encouraged.

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POST SECOND-LINE THERAPY MANAGEMENThh,ii FOLLOW-UP RECURRENCE

No residual mass or See Follow-up For
residual mass for Seminoma, recurrence,
≤3 cm and normal Surveillance Table 3 see Third-Line
serum AFP and (TEST-A 2 of 2) Therapy (SEM-7)
beta-hCG

Surveillance See Follow-up for

Negative Surveillance Seminoma, Table 4
(TEST-A 2 of 2)
Residual or
• Chest/ mass
abdomen/ (>3 cm) Repeat FDG-PET/ Complete
pelvis CT and Consider Indeterminate CT or CT scan in 6–8 resection
scand or normal FDG-PET/CT weekscc
MRI serum scan from skull Positive for viable Incomplete Third-Line Therapy
• Serum AFP and base to mid- seminomaff (SEM-7)
resection
tumor beta-hCG thigh (6 wks Resection or
markers or more post- of residual Progression
chemotherapy) Positivebb massjj or
Biopsy See Follow-up for
Negative for viable Seminoma, Table 4
seminomaff (TEST-A 2 of 2)
Progressive disease (growing Third-Line Therapy (SEM-7)
mass or rising markers)b Recurrence,
See Third-Line
Therapy (SEM-7)
b Mildly elevated, non-rising AFP levels may not indicate presence of germ
cell tumor. Decisions to treat should not be based on AFP values <20 ng/ ff In rare cases, nonseminomatous elements will be identified. If they are non-
mL. More highly elevated AFP levels generally indicate the presence of teratomatous, then proceed in the same fashion as for viable seminoma above.
nonseminomatous tumor elements. Further workup should be considered hh To assess response after treatment, CT with contrast or MRI with and without contrast
before initiating treatment for mildly elevated beta-hCG (generally <20 IU/L) of chest/abdomen/pelvis and any other sites of disease is recommended. FDG-PET
since other factors, including hypogonadism and marijuana use, can cause from skull base to mid thigh may also be considered in assessing treatment response
false-positive results. See Discussion. and residual masses following chemotherapy in patients with seminoma.
d CT with contrast or MRI with and without contrast. ii Includes best supportive care and palliative care. See NCCN Guidelines for Palliative
bb Principles of Imaging (TEST-I). Care.
cc If still indeterminate, recommend following with CT scan or biopsy. jj Consider referral to a high-volume center.

Note: All recommendations are category 2A unless otherwise indicated.

Clinical Trials: NCCN believes that the best management of any patient with cancer is in a clinical trial. Participation in clinical trials is especially encouraged.

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RECURRENCEgg THIRD-LINE THERAPYhh,ii

Clinical trial (preferred)

or
Prior first- and second- High-dose chemotherapykk
line conventional dose or
chemotherapy Conventional dose third-line chemotherapykk
or
Microsatellite instability/mismatch repair (MSI/
MMR) or tumor mutational burden (TMB) testing
if progression after high-dose chemotherapy or
Prior third-line therapy
second-line or
chemotherapy RT in select patientsm

Clinical trial (preferred)

or
Conventional dose third-line chemotherapykk
Prior high-dose
or
chemotherapy
MSI/MMR or TMB testing if progression after high-dose chemotherapy or
third-line therapy
or
RT in select patientsm
and/or
Best supportive care (See NCCN Guidelines for Palliative Care)

m See Principles of Radiotherapy for Pure Testicular Seminoma (TEST-C).

gg It is preferred that patients with recurrent seminoma be treated at centers with expertise in the management of this disease.
hh To assess response after treatment, CT with contrast or MRI with and without contrast of chest/abdomen/pelvis and any other
sites of disease is recommended. FDG-
PET from skull base to mid thigh may also be considered in assessing treatment response and residual masses following chemotherapy in patients with seminoma.
ii Includes best supportive care and palliative care. See NCCN Guidelines for Palliative Care.
kk See Third-Line Chemotherapy Regimens for Metastatic Germ Cell Tumors (TEST-G).

Note: All recommendations are category 2A unless otherwise indicated.

Clinical Trials: NCCN believes that the best management of any patient with cancer is in a clinical trial. Participation in clinical trials is especially encouraged.

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Testicular Cancer - Nonseminoma Discussion

PATHOLOGIC DIAGNOSIS POSTDIAGNOSTIC WORKUPb CLINICAL STAGE

Stage I with and

without risk Primary Treatment (NSEM-2)
factorsf,g

• Chest/abdomen/pelvis CTc or MRI

• Repeat beta-hCG, LDH, AFP
NSGCT (includes mixed
because staging is based on post-
seminoma/nonseminoma
orchiectomy valuesa,d Stage IIA, IIB Primary Treatment (NSEM-3)
tumors and seminoma
• Brain MRI,c if clinically indicatede
histology with elevated AFP)a
• Recommend sperm banking, if
clinically indicated

Stage IS, IIC,

IIIA,f IIIB,f IIIC,f Primary Treatment (NSEM-6)
and brain
metastasis

a Mildly elevated, non-rising AFP levels may not indicate presence of germ cell tumor.
Decisions to treat should not be based on AFP values <20 ng/mL. More highly
elevated AFP levels generally indicate the presence of nonseminomatous tumor
elements. Further workup should be considered before initiating treatment for mildly
elevated beta-hCG (generally <20 IU/L) since other factors, including hypogonadism
and marijuana use, can cause false-positive results. See Discussion.
b FDG-PET/CT scan is not clinically indicated for nonseminoma. e Eg, beta-hCG >5000 IU/L, extensive lung metastasis, predominance
c CT with contrast and MRI with and without contrast. of choriocarcinoma, neurologic symptoms, non-pulmonary visceral
d Elevations of AFP either pre- or post-orchiectomy indicate the presence of metastasis, or AFP >10,000 ng/mL.
nonseminomatous elements. For patents with elevated pre-orchiectomy beta- f The panel recommends staging tumors with discontinuous invasion of the
hCG levels, beta-hCG levels should be followed with repeated determinations after spermatic cord as pT3 (high-risk stage I) and not as M1 (stage III) as is
orchiectomy to determine their trajectory and, if declining, their nadir. The expected half- recommended in the 8th edition of the AJCC Cancer Staging Manual. If
life for beta-hCG is 3 days or less. For patients with normal imaging (ie, stage I), rising surveillance is elected, the pelvis should be included in the imaging due to
or persistently elevated beta-hCG levels generally indicate the presence of metastatic a higher risk of pelvic relapses in these patients. See Discussion.
disease (stage IS). For patients with metastatic disease to the retroperitoneum or g Risk factors for recurrence include lymphovascular invasion or invasion
beyond (stage II or III), highly elevated post-orchiectomy beta-HCG (>1000 IU/L) levels of spermatic cord or scrotum. Some centers consider predominance of
may indicate the presence of non-seminomatous tumor elements. See Discussion. embryonal carcinoma as an additional risk factor for relapse.

Note: All recommendations are category 2A unless otherwise indicated.

Clinical Trials: NCCN believes that the best management of any patient with cancer is in a clinical trial. Participation in clinical trials is especially encouraged.

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CLINICAL PRIMARY TREATMENTh,i

STAGE

Surveillance (preferred) See Follow-up for Nonseminoma, Table 5 (TEST-B 1 of 3)

or
Stage I without Nerve-sparing RPLNDj,k,l Postsurgical Management (NSEM-5)
risk factorsg,i
or
Adjuvant chemotherapym:
BEP for 1 cycle See Follow-up for Nonseminoma, Table 7 (TEST-B 2 of 3)

Surveillance See Follow-up for Nonseminoma, Table 6 (TEST-B 1 of 3)

or
Stage I with Adjuvant chemotherapym:
risk factorsg,i BEP for 1 cycle See Follow-up for Nonseminoma, Table 7 (TEST-B 2 of 3)

or
Nerve-sparing RPLNDj,k,l Postsurgical Management (NSEM-5)
Persistent
Stage
marker Primary Treatment (NSEM-6)
IS
elevationa
a Mildly elevated, non-rising AFP levels may not indicate presence of germ cell
tumor. Decisions to treat should not be based on AFP values <20 ng/mL. More i RPLND is preferred as primary treatment for tumors with transformed teratoma.
highly elevated AFP levels generally indicate the presence of nonseminomatous Patients with stage I pure teratoma and normal markers should receive either
tumor elements. Further workup should be considered before initiating treatment surveillance or RPLND. See Discussion.
for mildly elevated beta-hCG (generally <20 IU/L) since other factors, including j RPLND is recommended within 4 weeks of CT scan and within 7–10 days of
hypogonadism and marijuana use, can cause false-positive results. See confirmation of normal tumor markers.
Discussion. k See Principles of Surgery for Germ Cell Tumors (TEST-H).
g Risk factors for recurrence include lymphovascular invasion or invasion of l Recommend referral to a high-volume center.
spermatic cord or scrotum. Some centers consider predominance of embryonal m Recommend imaging within the 4 weeks prior to the initiation of chemotherapy to
carcinoma as an additional risk factor for relapse. confirm staging, even if the scan was done previously. See Principles of Imaging
h Treatment options listed based on preference. See Discussion. (TEST-I).

Note: All recommendations are category 2A unless otherwise indicated.

Clinical Trials: NCCN believes that the best management of any patient with cancer is in a clinical trial. Participation in clinical trials is especially encouraged.

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Testicular Cancer - Nonseminoma Discussion

CLINICAL STAGE PRIMARY TREATMENT

Postsurgical
Nerve-sparing RPLNDj,k,l Management (NSEM-5)

Markers negative or
Post First-Line
Stage First-Line chemotherapyp: Chemotherapy
IIAn,o BEP for 3 cycles or EP for 4 cyclesq Management (NSEM-4)
Persistent marker
See Primary Treatment (NSEM-6)
elevationa
Post First-Line
First-Line chemotherapyp: Chemotherapy
BEP for 3 cycles or EP for 4 cyclesq Management (NSEM-4)
Lymph node metastases,
within lymphatic drainage or
sites Postsurgical
Markers Nerve-sparing RPLNDj,k,l in highly Management (NSEM-5)
negative selected casesr
Multifocal, symptomatic, or Post First-Line
Stage First-Line chemotherapyp: Chemotherapy
lymph node metastases with
IIBo BEP for 3 cycles or EP for 4 cyclesq Management (NSEM-4)
aberrant lymphatic drainage

Persistent marker elevationa Primary Treatment (NSEM-6) Preferred Regimens

BEP = Bleomycin/etoposide/cisplatin
EP = Etoposide/cisplatin

a Mildly elevated, non-rising AFP levels may not indicate presence of germ cell tumor. n For select cases of clinical stage IIA disease with borderline retroperitoneal lymph
Decisions to treat should not be based on AFP values <20 ng/mL. More highly nodes, waiting 4 weeks and repeating imaging (CT or MRI) to confirm staging
elevated AFP levels generally indicate the presence of nonseminomatous tumor before initiating treatment can be considered.
elements. Further workup should be considered before initiating treatment for mildly o RPLND is preferred as primary treatment for stage II tumors with somatic type
elevated beta-hCG (generally <20 IU/L) since other factors, including hypogonadism malignancy (previously referred to as transformed teratoma). See Discussion.
and marijuana use, can cause false-positive results. See Discussion. p First-Line Chemotherapy Regimens for Germ Cell Tumors (TEST-E).
j RPLND is recommended within 4 weeks of CT scan and within 7–10 days of q Consider
 a bleomycin-free regimen in patients at increased risk for bleomycin
confirmation of normal tumor markers. toxicity, such as those with reduced GFR or older age. See Discussion.
k See Principles of Surgery for Germ Cell Tumors (TEST-H). r RPLND should be considered for stage II tumors with teratoma predominance in
l Recommend referral to a high-volume center. patients with normal markers.

Note: All recommendations are category 2A unless otherwise indicated.

Clinical Trials: NCCN believes that the best management of any patient with cancer is in a clinical trial. Participation in clinical trials is especially encouraged.

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POST FIRST-LINE CHEMOTHERAPY MANAGEMENT FOLLOW-UP

Surveillance
(preferred)
Negative markers,
no mass, or or
residual mass <1
cm (transaxial Nerve-sparing
long axis) on CT bilateral See Follow-
scans RPLNDj,k,l up for
in selected cases Teratoma or Nonseminoma,
• Abdomen/ Surveillance
(category 2B) necrosis Table 8
Stage IIA, pelvis CTb,c
IIB treated or MRI (TEST-B 2 of 3)
with first-line • Consider Chemotherapy
chemotherapy chest CTb,c Residual (preferred) for
2 cycles (EP or See Follow-
or chest embryonal,
TIP or VIP or up for
x-ray yolk sac,
VeIP)p,t Nonseminoma,
choriocarcinoma,
Table 8
Negative markers, or seminoma or
(TEST-B 2 of 3)
residual mass ≥1 Nerve-sparing element Surveillance for
cm (transaxial bilateral select patientsu
long axis) on CT RPLNDj,k,l
scans

p First-Line Chemotherapy Regimens for Germ Cell Tumors (TEST-E).

b FDG-PET/CT scan is not clinically indicated for nonseminoma. s Craniocaudal axis should not be used.
c CT with contrast and MRI with and without contrast. t Second-Line Chemotherapy Regimens for Metastatic Germ Cell Tumors
j RPLND is recommended within 4 weeks of CT scan and within 7–10 days of (TEST-F).
confirmation of normal tumor markers. u Surveillanceis a reasonable alternative to chemotherapy for patients with
k See Principles of Surgery for Germ Cell Tumors (TEST-H). residual masses that have been completely resected if all of the residual
l Recommend referral to a high-volume center. masses have less than 10% viable cancer cells in the resected tissue.

Note: All recommendations are category 2A unless otherwise indicated.

Clinical Trials: NCCN believes that the best management of any patient with cancer is in a clinical trial. Participation in clinical trials is especially encouraged.

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POSTSURGICAL MANAGEMENT FOLLOW-UP

pN0 Surveillance See Follow-up for Nonseminoma,

Table 9 (TEST-B 3 of 3)

Surveillance (preferred) See Follow-up for Nonseminoma,

Table 10 (TEST-B 3 of 3)
pN1 or
See Follow-up for Nonseminoma,
Chemotherapyp: EP for 2 cycles Table 9 (TEST-B 3 of 3)
Stage IA, IB with and
without risk factors,g
IIA, IIB treated with
primary nerve-sparing
RPLND See Follow-up for Nonseminoma,
Chemotherapyp: EP for 2 cycles Table 9 (TEST-B 3 of 3)
pN2 or
See Follow-up for Nonseminoma,
Surveillancev Table 10 (TEST-B 3 of 3)

Chemotherapy
(preferred)p,w: See Follow-up for Nonseminoma,
pN3
BEPq for 3 cycles Table 9 (TEST-B 3 of 3)
or
EP for 4 cycles
or See Follow-up for Nonseminoma,
Surveillance Table 10 (TEST-B 3 of 3)

pN1, pN2
g Risk factors for recurrence include lymphovascular q Consider a bleomycin-free regimen in patients at Preferred Regimens
invasion or invasion of spermatic cord or scrotum. increased risk for bleomycin toxicity, such as those with EP = Etoposide/cisplatin
Some centers consider predominance of reduced GFR or older age. See Discussion.
v Surveillance is preferred for patients who have pure pN3
embryonal carcinoma as an additional risk factor Preferred Regimens
for relapse. teratoma.
p First-Line Chemotherapy Regimens for Germ Cell w This is a rare circumstance. BEP for 2 cycles is an BEP = Bleomycin/etoposide/cisplatin
Tumors (TEST-E). option. EP = Etoposide/cisplatin

Note: All recommendations are category 2A unless otherwise indicated.

Clinical Trials: NCCN believes that the best management of any patient with cancer is in a clinical trial. Participation in clinical trials is especially encouraged.

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CLINICAL PRIMARY TREATMENTx POSTCHEMOTHERAPY FOLLOW-UP RECURRENCE

STAGE MANAGEMENT

First-Line If original
Good risky chemotherapyp: stage, Surveillance
Stage IS BEP for 3 cyclesq Complete stage IS
Stage IIA, S1 (category 1) response, Surveillance
Stage IIB, S1 See For recurrence,
or negative Follow-up for
Stage IIC markers or see Second-Line
EP for 4 cycles If original Nonseminoma,
Stage IIIA (category 1) stage, Therapy (NSEM-8)
Nerve-sparing Table 8
See Discussion T any N1–3, bilateral (TEST-B 2 of 3)
M0–1 RPLNDj,k,l
in selected cases
(category 2B)
First-Line
chemotherapyp:
Intermediate BEP for 4 cyclesq,aa
risk and (category 1)
poor risky,z or Partial response, residual masses with
Stage IIIB VIP for 4 cycles normal AFP and beta-hCG levels
Stage IIIC (category 1) OR Postchemotherapy Management (NSEM-7)
Partial response, residual masses with
abnormal AFP and/or beta-hCG levelsl
Preferred Regimens
Brain First-Line chemotherapy as for poor-risk BEP = Bleomycin/etoposide/cisplatin
metastases diseasep,z ± RT ± surgery, if clinically indicated EP = Etoposide/cisplatin
j RPLND
Other Recommended Regimens
is recommended within 4 weeks of CT scan and within 7–10 days of confirmation of VIP = Etoposide/ifosfamide/cisplatin
normal tumor markers.
k See Principles of Surgery for Germ Cell Tumors (TEST-H).
l Recommend referral to a high-volume center.
p First-Line Chemotherapy Regimens for Germ Cell Tumors (TEST-E). y Risk Classification for Advanced Disease (TEST-D).
q Consider a bleomycin-free regimen in patients at increased risk for bleomycin toxicity, such as z Referral to a high-volume center is recommended for patients
those with reduced GFR or older age. See Discussion. with poor risk disease. Consider referral to a high-volume center
x To
 assess response after treatment, CT with contrast or MRI with and without contrast of chest/
for patients with intermediate risk disease.
abdomen/pelvis and any other sites of disease is recommended. FDG-PET has no role in aa If intermediate risk is based only on LDH 1.5–3 times the upper
assessing treatment response and residual masses following chemotherapy in patients with limit of normal (ULN), then BEP for 3 cycles or EP for 4 cycles
nonseminoma. can be considered.

Note: All recommendations are category 2A unless otherwise indicated.

Clinical Trials: NCCN believes that the best management of any patient with cancer is in a clinical trial. Participation in clinical trials is especially encouraged.

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RESPONSE AFTER POSTCHEMOTHERAPY FOLLOW-UP RECURRENCE

PRIMARY TREATMENT MANAGEMENT

Teratoma or necrosis Surveillance

Partial response, Surgical
residual masses resection of
with normal AFP all residual
and beta-hCG levels massesl,cc
Residual embryonal,
yolk sac, Chemotherapy for 2
choriocarcinoma, or cycles (EPdd or TIP or VIP
seminoma element or VeIP)p,t
See For
Follow-up for recurrence,
Nonseminoma, see Second-
Elevated and rising AFP Second-Line Table 8 Line Therapy
and/or beta-hCG levelsa Therapy (TEST-F) (TEST-B 2 of 3) (NSEM-8)

Partial
response,
residual
masses with Elevated but stable AFP
and/or beta-hCG levelsa Close surveillance
abnormal
AFP and/or
beta-hCG Teratoma or Preferred Regimens
levelsl,bb Mildly necrosis
Surveillance
EP = Etoposide/cisplatin
elevated and Consider TIP = Paclitaxel/ifosfamide/cisplatin
normalizing surgical VIP = Etoposide/ifosfamide/cisplatin
AFP and/ resection of Residual VeIP = Vinblastine/ifosfamide/cisplatin
or beta-hCG all residual embryonal,
levelsa massesl yolk sac,
Chemotherapy for 2 cycles
chorio-
(EPdd or TIP or VIP or VeIP)p,t
carcinoma,
or seminoma Footnotes
element on NSEM-7A
Note: All recommendations are category 2A unless otherwise indicated.
Clinical Trials: NCCN believes that the best management of any patient with cancer is in a clinical trial. Participation in clinical trials is especially encouraged.

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FOOTNOTES

a Mildly elevated, non-rising AFP levels may not indicate presence of germ cell tumor. Decisions to treat should not be based on AFP values <20 ng/mL. More highly
elevated AFP levels generally indicate the presence of nonseminomatous tumor elements. Further workup should be considered before initiating treatment for
mildly elevated beta-hCG (generally <20 IU/L) since other factors, including hypogonadism and marijuana use, can cause false-positive results. See Discussion.
l Recommend referral to a high-volume center.
p First-Line Chemotherapy Regimens for Germ Cell Tumors (TEST-E).
t Second-Line Chemotherapy Regimens for Metastatic Germ Cell Tumors (TEST-F).
bb Consider brain imaging and testicular ultrasound in patients with elevated or rising markers after primary or secondary chemotherapy to evaluate for occult brain
metastases or contralateral primary disease.
cc If there is a teratoma with somatic-type malignancy, consider histology-directed therapy and referral to an academic center with a high-volume germ cell tumor unit.
dd Consider EP for low-volume residual disease.

Note: All recommendations are category 2A unless otherwise indicated.

Clinical Trials: NCCN believes that the best management of any patient with cancer is in a clinical trial. Participation in clinical trials is especially encouraged.

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RECURRENCEee SECOND-LINE THERAPYx,ff FOLLOW-UP

• Clinical trial (preferred)

• Chemotherapyt
Early relapse (recurrence Conventional-dose therapy (VeIP for 4 cycles or
≤2 years after completion of TIP for 4 cycles)
primary treatment) High-dose chemotherapy
• Consider surgical treatment if solitary site
• Recommend sperm banking if clinically indicated
Prior first-line Post Second-
chemotherapy Line Therapy
Management
• Surgical treatment, if resectable (preferred) (NSEM-9)
• Clinical trial, if unresectable
Late relapse (recurrence >2 • Chemotherapyt
years after completion of Conventional-dose therapy (VeIP for 4 cycles or
primary treatment) TIP for 4 cycles)
High-dose chemotherapy
• Recommend sperm banking if clinically indicated

Treat per risk status on (NSEM-6)

No prior first-line chemotherapy and
Recommend sperm banking

Prior adjuvant therapy

(1 cycle of BEP only) First-Line chemotherapy (NSEM-6)
Preferred Regimens
• High-dose chemotherapyt
• TIP = Paclitaxel/ifosfamide/cisplatin
• VeIP = Vinblastine/ifosfamide/cisplatin
t Second-Line Chemotherapy Regimens for Metastatic Germ Cell Tumors (TEST-F).
x To assess response after treatment, CT with contrast or MRI with and without contrast of chest/abdomen/pelvis and any other sites of disease is recommended. FDG-
PET has no role in assessing treatment response and residual masses following chemotherapy in patients with nonseminoma.
ee It is preferred that patients with recurrent nonseminoma be treated at centers with expertise in the management of this disease.
ff Includes best supportive care and palliative care. See NCCN Guidelines for Palliative Care.

Note: All recommendations are category 2A unless otherwise indicated.

Clinical Trials: NCCN believes that the best management of any patient with cancer is in a clinical trial. Participation in clinical trials is especially encouraged.

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RECURRENCEee POST SECOND-LINE THERAPY MANAGEMENTx,ff FOLLOW-UP RECURRENCEee

Surveillance
Complete response, or
negative markers Nerve-sparing bilateral RPLNDj,k,l
Surveillance
in selected cases (category 2B)
Teratoma Surveillance
or necrosis
Partial response, Surgical
residual masses with resection of Residual
Prior normal AFP and beta- all residual embryonal,
second- hCG levels massesl,cc yolk sac,
line choriocarcinoma, Surveillance
See Follow- For
therapy or seminoma up for
element recurrence,
Nonseminoma, see Third-
Elevated and rising AFP Third-Line Table 8 Line Therapy
and/or beta-hCG levela Therapy (TEST-B 2 of 3) (NSEM-10)
Partial (TEST-G)
response,
residual Close
Elevated but stable AFP
masses with surveillance
and/or beta-hCG levelsa
abnormal
AFP and/or Teratoma
Mildly or necrosis Surveillance
beta-hCG Consider
elevated and
levelsl,aa surgical
normalizing Residual embryonal,
resection of
AFP and/ yolk sac,
all residual Surveillance
or beta-hCG massesl choriocarcinoma, or
levelsa seminoma element
x To assess response after treatment, CT with contrast or MRI with and without contrast
a Mildly elevated, non-rising AFP levels may not indicate presence of germ cell tumor. of chest/abdomen/pelvis and any other sites of disease is recommended. FDG-
Decisions to treat should not be based on AFP values <20 ng/mL. More highly PET has no role in assessing treatment response and residual masses following
elevated AFP levels generally indicate the presence of nonseminomatous tumor chemotherapy in patients with nonseminoma.
elements. Further workup should be considered before initiating treatment for mildly aa If intermediate risk is based only on LDH 1.5–3 times the ULN, then BEP for 3 cycles or EP for
elevated beta-hCG (generally <20 IU/L) since other factors, including hypogonadism 4 cycles can be considered.
and marijuana use, can cause false-positive results. See Discussion. cc If there is a teratoma with somatic-type malignancy, consider histology-directed therapy and
j RPLND is recommended within 4 weeks of CT scan and within 7–10 days of referral to an academic center with a high-volume germ cell tumor unit.
confirmation of normal tumor markers. ee It is preferred that patients with recurrent nonseminoma be treated at centers with expertise in
k See Principles of Surgery for Germ Cell Tumors (TEST-H). the management of this disease.
l Recommend referral to a high-volume center. ff Includes best supportive care and palliative care. See NCCN Guidelines for Palliative Care.

Note: All recommendations are category 2A unless otherwise indicated.

Clinical Trials: NCCN believes that the best management of any patient with cancer is in a clinical trial. Participation in clinical trials is especially encouraged.

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RECURRENCEee THIRD-LINE THERAPYx,ff

Clinical trial (preferred)

or
Prior first- and second-line
High-dose chemotherapygg
conventional dose chemotherapy
or
Consider surgical treatment if solitary site

Clinical trial (preferred)

or
Conventional dose third-line chemotherapygg
Prior or
second-line Prior high-dose chemotherapy
Consider surgical treatment if solitary site
chemotherapy or
MSI/MMR or TMB testing if progression after high-dose
chemotherapy or third-line therapygg

Surgical treatment, if resectable (preferred)

Late relapse or
(recurrence >2 years after completion Chemotherapygg
of second-line chemotherapy) • Conventional-dose therapy
• High-dose chemotherapy (if not previously received)

x To assess response after treatment, CT with contrast or MRI with and without contrast of chest/abdomen/pelvis and any other sites of disease is recommended. FDG-
PET has no role in assessing treatment response and residual masses following chemotherapy in patients with nonseminoma.
ee It is preferred that patients with recurrent nonseminoma be treated at centers with expertise in the management of this disease.
ff Includes best supportive care and palliative care. See NCCN Guidelines for Palliative Care.
gg Third-Line Chemotherapy Regimens for Metastatic Germ Cell Tumors (TEST-G).

Note: All recommendations are category 2A unless otherwise indicated.

Clinical Trials: NCCN believes that the best management of any patient with cancer is in a clinical trial. Participation in clinical trials is especially encouraged.

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Testicular Cancer - Pure Seminoma Discussion

FOLLOW-UP FOR SEMINOMA

No single follow-up plan is appropriate for all patients. The follow-up for seminoma tables is to provide guidance, and should be modified for the individual
patient based on sites of disease, biology of disease, and length of time on treatment and may be extended beyond 5 years at the discretion of the physician.
Reassessment of disease activity should be performed in patients with new or worsening signs or symptoms of disease, regardless of the time interval from
previous studies. Further study is required to define optimal follow-up duration. See NCCN Guidelines for Survivorship.

Table 1 Clinical Stage I Seminoma: Surveillance After Orchiectomy

Year (at month intervals)
1 2 3 4 5d

H&Pa,b Every 3–6 mo Every 6 mo Every 6–12 mo Annually Annually

Abdomen ± Pelvis At 4–6, If Recurrence, treat according to

Every 6 mo Every 6–12 mo Every 12–24 mo extent of disease at relapse
CTc or MRIe,f and 12 mo

Chest x-ray As clinically indicated, consider chest CT with contrast in symptomatic patients.

Table 2 Clinical Stage I Seminoma: Surveillance After Adjuvant Treatment (Chemotherapy or Radiation)
Year (at month intervals)
1 2 3 4 5d

H&Pa,b Every 6–12 mo Every 6–12 mo Annually Annually Annually

Abdomen ± Pelvis If Recurrence, treat according to

Annually Annually Annually —— extent of disease at relapse
CTc or MRIe,f

Chest x-ray As clinically indicated, consider chest CT with contrast in symptomatic patients.

c With or without contrast.

d CT is not recommended beyond 5 years unless clinically indicated.
a Serum tumor markers are optional. e Principles of Imaging (TEST-I).
b Testicular ultrasound for any equivocal exam. f With and without contrast.

Note: All recommendations are category 2A unless otherwise indicated.

Clinical Trials: NCCN believes that the best management of any patient with cancer is in a clinical trial. Participation in clinical trials is especially encouraged.
TEST-A
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FOLLOW-UP FOR SEMINOMA

Table 3 Clinical Stage IIA and Non-Bulky IIB Seminoma: Surveillance After Radiotherapy or Postchemotherapyg
Year (at month intervals)
1 2 3 4 5d

H&Pa,b Every 3 mo Every 6 mo Every 6 mo Every 6 mo Every 6 mo

CTh,i or MRIf If Recurrence, treat according to

At 3 mo, then extent of disease at relapse
of Abdomen + Annually Annually As clinically indicated
at 9 or 12 mo
Pelvis

Chest x-rayj Every 6 mo Every 6 mo ——

Table 4 Clinical Stage IIA Seminoma: Post-Primary RPLND and NOT Treated with Adjuvant Chemotherapy
Year (at month intervals)
1 2 3 4 5d

H&Pa,b Every 4 mo Every 6 mo Every 6 mo Every 6 mo Every 6 mo

CTh,i or MRIf If Recurrence, treat according to

of Abdomen + Every 4 mo Every 6 mo Annually As clinically indicated extent of disease at relapse
Pelvis

Chest x-rayj Every 4 mo Every 6 mo Annually As clinically indicated

a Serum tumor markers are optional.

b Testicular ultrasound for any equivocal exam. i An MRI can be considered to replace an abdomen/pelvis CT. The MRI protocol
d CT is not recommended beyond 5 years unless clinically indicated. should include all the nodes that need to be assessed. See Principles of Imaging
f With and without contrast. (TEST-I).
g Assuming no residual mass or residual mass <3 cm and normal tumor markers. j Chest x-ray may be used for routine follow-up, but chest CT with contrast is
h With contrast. preferred in the presence of thoracic symptoms.

Note: All recommendations are category 2A unless otherwise indicated.

Clinical Trials: NCCN believes that the best management of any patient with cancer is in a clinical trial. Participation in clinical trials is especially encouraged.
TEST-A
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FOLLOW-UP FOR SEMINOMA

Table 5 Clinical Stage IIA Seminoma: Post-Primary RPLND and Treated with Adjuvant Chemotherapy
Year (at month intervals)
1 2 3 4 5d

H&Pa,b Every 3 mo Every 6 mo Every 6 mo Every 6 mo Every 6 mo If Recurrence, treat according to

extent of disease at relapse
CTh,i or MRIf
of Abdomen + Every 6 mo Annually As clinically indicated
Pelvis

Chest x-rayj Every 6 mo Annually Annually Annually Annually

Table 6 Bulky Clinical Stage IIB, IIC, and Stage III Seminoma: Surveillance Postchemotherapy
Year (at month intervals)
1 2 3 4 5d
H&P and
Every 2 mo Every 3 mo Every 6 mo Every 6 mo Annually
markersb
If Recurrence, see Second-Line
CTh,i,k,l,m or MRIf Therapy (SEM-5)
As clinically
of Abdomen/ Every 4 mo Every 6 mo Annually Annually
indicated
Pelvis

Chest x-rayj Every 2 mon Every 3 mon Annually Annually Annually

a Serum tumor markers are optional.
b Testicular ultrasound for any equivocal exam. k Patients with FDG-PET-negative residual mass measuring >3 cm following
d CT is not recommended beyond 5 years unless clinically indicated. chemotherapy should undergo an MRI with and without contrast or abdomen/
f With and without contrast. pelvis CT scan with contrast every 6 months for the first year, then annually for 5
h With contrast. years.
i An MRI can be considered to replace an abdomen/pelvis CT. The MRI protocol l Patients with residual masses may require more frequent imaging based on
should include all the nodes that need to be assessed. See Principles of Imaging clinical judgment.
(TEST-I). m FDG-PET/CT scan of skull base to mid-thigh as clinically indicated.
j Chest x-ray may be used for routine follow-up, but chest CT with contrast is n Add chest CT with contrast if supradiaphragmatic disease present at diagnosis.
preferred in the presence of thoracic symptoms.

Note: All recommendations are category 2A unless otherwise indicated.

Clinical Trials: NCCN believes that the best management of any patient with cancer is in a clinical trial. Participation in clinical trials is especially encouraged.
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Testicular Cancer - Nonseminoma Discussion

FOLLOW-UP FOR NONSEMINOMA

No single follow-up plan is appropriate for all patients. The follow-up for nonseminoma tables is to provide guidance, and should be modified for the
individual patient based on sites of disease, biology of disease, and length of time on treatment and may be extended beyond 5 years at the discretion of the
physician. Reassessment of disease activity should be performed in patients with new or worsening signs or symptoms of disease, regardless of the time
interval from previous studies. Further study is required to define optimal follow-up duration.
Table 6 Clinical Stage I without Risk Factors,a NSGCT: Active Surveillance
Year (at month intervals)
1 2 3 4 5
H&P and
Every 2 mo Every 3 mo Every 4–6 mo Every 6 mo Annually
markersb
CTc,d or MRIe If Recurrence, treat according to
of Abdomen Every 4–6 mo Every 6 mo Annually As clinically indicated extent of disease at relapse
± Pelvis

At mo 4 and As clinically As clinically As clinically

Chest x-rayf Annually
12 indicated indicated indicated

Table 7 Clinical Stage I with Risk Factors,a NSGCT: Active Surveillance

Year (at month intervals)
1 2 3 4 5
H&P and
Every 2 mo Every 3 mo Every 4–6 mo Every 6 mo Annually
markersb
If Recurrence, treat according to
CTc,d or MRIe extent of disease at relapse
As clinically
of Abdomen Every 4 mo Every 4–6 mo Every 6 mo Annually
indicated
± Pelvis

As clinically
Chest x-rayf Every 4 mo Every 4–6 mo Every 6 mo Annually
indicated
d An MRI can be considered to replace an abdomen/pelvis CT. The MRI protocol
a Risk factors for recurrence include lymphovascular invasion or invasion of should include all the nodes that need to be assessed. See Principles of Imaging
spermatic cord or scrotum. Some centers consider predominance of embryonal (TEST-I).
carcinoma as an additional risk factor for relapse. e With and without contrast.
b Testicular ultrasound for any equivocal exam. f Chest x-ray may be used for routine follow-up, but chest CT with contrast is
c With contrast. preferred in the presence of thoracic symptoms.
Note: All recommendations are category 2A unless otherwise indicated.
Clinical Trials: NCCN believes that the best management of any patient with cancer is in a clinical trial. Participation in clinical trials is especially encouraged.
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FOLLOW-UP FOR NONSEMINOMA

Table 8 Clinical Stage IA/B NSGCT: Treated with 1 Cycle of Adjuvant BEP Chemotherapy or Primary RPLND
Year (at month intervals)
1 2 3 4 5
H&P and
Every 3 mo Every 3 mo Every 6 mo Every 6 mo Annually
markersb
If Recurrence, see treat according
CTc,d or MRIe to extent of disease at relapse
of Abdomen Annually Annuallyg — — —
± Pelvis

Chest x-rayf Every 6–12 mo Annually — — —

Table 9 Clinical Stage II–III NSGCT: Surveillance After Complete Response to Chemotherapy ± Postchemotherapy RPLNDg
Year (at month intervals)
1 2 3 4 5
H&P and
Every 2 mo Every 3 mo Every 6 mo Every 6 mo Every 6 mom
markersb If Recurrence, see Second-Line
Therapy (NSEM-8) or Third-Line
CTc,d,i or MRIe
Therapy (NSEM-10)
of Abdomen ± Every 6 mo Every 6–12 mo Annually As clinically indicatedl
Pelvis

Chest x-rayf,j Every 6 mo Every 6 mo Annuallyk Annuallyk —

b Testicular ultrasound for any equivocal exam. i

c With contrast. Patients with clinical stage II disease treated with chemotherapy
d An MRI can be considered to replace an abdomen/pelvis who undergo postchemotherapy RPLND and are found to have pN0
CT. The MRI protocol should include disease or pN1 pure teratoma need only 1 CT scan at postoperative
all the nodes that need to be assessed. See Principles of Imaging (TEST-I). month 3–4 and then as clinically indicated. See Discussion.
e With and without contrast. j Chest CT with contrast if supradiaphragmatic disease at baseline.
f Chest x-ray may be used for routine follow-up, but chest CT with contrast is preferred in the k Chest x-ray is optional at months 36 and 48.
presence of thoracic symptoms. l For patients with unresected residual masses or resected residual
g Optional for patients treated with primary RPLND.
h Patients who have an incomplete response to chemotherapy require more frequent imaging masses containing viable cancer.
m Consider annual tumor markers for years 5–10.
than is listed on this table.
Note: All recommendations are category 2A unless otherwise indicated.
Clinical Trials: NCCN believes that the best management of any patient with cancer is in a clinical trial. Participation in clinical trials is especially encouraged.
TEST-B
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FOLLOW-UP FOR NONSEMINOMA

Table 10 Pathologic Stage IIA/B NSGCT: Post-Primary RPLND and Treated with Adjuvant Chemotherapy
Year (at month intervals)
1 2 3 4 5
H&P and
Every 6 mo Every 6 mo Annually Annually Annually
markersb
CTc,d,n or MRIe If Recurrence, see
4 mo after Second-Line Therapy (NSEM-8)
of Abdomen/ As clinically indicated
Pelvis
RPLND

Chest x-rayf Every 6 mo Annually Annually Annually Annually

Table 11 Pathologic Stage IIA/B NSGCT: Post-Primary RPLND and NOT Treated with Adjuvant Chemotherapyo
Year (at month intervals)
1 2 3 4 5
H&P and
Every 2 mo Every 3 mo Every 4 mo Every 6 mo Annually
markersb
If Recurrence, see
CTc,d or MRIe First-Line therapy (NSEM-6)
of Abdomen/ At 3–4 mop Annually As clinically indicated
Pelvis
Every 3–6
Chest x-rayf Every 2–4 mo Annually Annually Annually
mo

b Testicular ultrasound for any equivocal exam. n Patients who undergo RPLND and are found to have pN0 disease or pN1 pure
c With contrast. teratoma need only 1 CT scan at postoperative month 3–4 and then as clinically
d An MRI can be considered to replace an abdomen/pelvis CT. The MRI protocol indicated. See Discussion.
should include all the nodes that need to be assessed. See Principles of Imaging o Patients with clinical stage IIA/IIB nonseminoma who undergo primary RPLND
(TEST-I). and are found to have pN0 disease (no cancer and no teratoma, pathologic stage
e With and without contrast. I) should revert to the surveillance schedule for low-risk NSGCT with the exception
f Chest x-ray may be used for routine follow-up, but chest CT with contrast is that only 1 CT scan is needed postoperatively around month 4 (Table 5).
preferred in the presence of thoracic symptoms. p This schedule assumes a complete resection has taken place.

Note: All recommendations are category 2A unless otherwise indicated.

Clinical Trials: NCCN believes that the best management of any patient with cancer is in a clinical trial. Participation in clinical trials is especially encouraged.
TEST-B
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Testicular Cancer - Pure Seminoma Discussion

PRINCIPLES OF RADIOTHERAPY FOR PURE TESTICULAR SEMINOMA

General Principles
• Modern radiotherapy involves smaller fields and lower doses than were used in the past. References are provided to support current
recommended management.
• The mean dose (Dmean) and dose delivered to 50% of the volume (D50%) of the kidneys, liver, and bowel are lower with CT-based
anteroposterior-posteroanterior (AP-PA) three-dimensional conformal radiation therapy (3D-CRT) than intensity-modulated radiation therapy
(IMRT).1 As a result, the risk of second cancers arising in the kidneys, liver, or bowel may be lower with 3D-CRT than IMRT, and IMRT is not
necessary.2 Proton therapy can also be considered. See Discussion.
• Timing of Radiotherapy:
Radiotherapy should start once the orchiectomy wound has fully healed.
Patients should be treated 5 days per week.
Patients who miss a fraction should be treated with the same total dose and with the same fraction size, extending the overall treatment
time slightly.
• Antiemetic medication significantly improves nausea. See NCCN Guidelines for Antiemesis. Antiemetic prophylaxis is encouraged at least 2
hours prior to each treatment, and some cases may require more frequent dosing.

Preparation for Radiotherapy

• A discussion of semen analysis and sperm banking prior to orchiectomy is recommended in patients who wish to preserve fertility.3,4
• If sperm banking is desired, it should be performed prior to imaging and the delivery of adjuvant therapy.

General Treatment Information

• Treatment Planning Principles
A non-contrast CT simulation should be performed with the patient supine, arms at the patient's sides, in the treatment position.
◊ Immobilization with a cast may be used to improve the reproducibility of patient setup.
◊ All patients, with the exception of those who have undergone bilateral orchiectomy, should be treated with a scrotal shield.

Stage I on TEST-C 2 of 5
Stage IIA, IIB on TEST-C 3 of 5
References on TEST-C 5 of 5
Note: All recommendations are category 2A unless otherwise indicated.
Clinical Trials: NCCN believes that the best management of any patient with cancer is in a clinical trial. Participation in clinical trials is especially encouraged.
TEST-C
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Testicular Cancer - Pure Seminoma Discussion

PRINCIPLES OF RADIOTHERAPY FOR PURE TESTICULAR SEMINOMA

Stage I
• Dose: For stages IA, IB: Recommended radiation dose regimens are listed in the table below for the minority of patients who prefer adjuvant
treatment, realizing that there is a high likelihood of salvage should a relapse occur during surveillance.5
Table 1
Total Dose (Gy) Dose per Fraction (Gy) Number of Fractions
20 (preferred) 2.0 10
25.5 1.5 17
19.8 1.8 11
21.6 1.8 12
• Para-aortic-Strip Fields6 - Field Arrangement:
In patients with no history of pelvic or scrotal surgery, para-aortic strip irradiation may be delivered with opposed AP-PA fields. The weights
of the fields may be equal.
◊ Recent nodal mapping studies suggest that fields should target the retroperitoneal lymph nodes but not necessarily the ipsilateral renal
hilar nodes (see Lateral borders).7,8
◊ Superior and inferior borders: Borders may be determined by bony anatomy.
◊ The superior border should be placed at the bottom of vertebral body T10/T11.9
◊ The inferior border should be placed at the inferior border of vertebral body L5.6,10
◊ Lateral borders:
▪ Conventionally, para-aortic-strip fields are approximately 10 cm wide, encompassing the tips of the transverse processes of the PA
vertebrae.
◊ The location of the kidneys within the para-aortic-strip fields varies from patient to patient.
▪ For patients whose kidneys are relatively medial, small renal blocks may be added at the level of T12. The right and left kidney D50%
should be ≤8 Gy (ie, no more than 50% of each kidney can receive ≥8 Gy).1 If only one kidney is present, the kidney D15% should be
≤20 Gy (ie, no more than 15% of the volume of the kidney can receive ≥20 Gy).1
▪ An alternative 3D-CRT planning technique is to base the lateral borders on vascular structures on a treatment planning CT scan
without contrast. The aorta and inferior vena cava (IVC) may be contoured on the CT scan; one should allow a 1.2- to 1.9-cm margin
on the aorta and IVC to include the para-aortic, paracaval, interaortocaval, and preaortic nodes in the clinical target volume.7,11
The planning target volume is then established by uniformly expanding the clinical target volume by 0.5 cm in all directions to
account for treatment setup errors.12 A uniform 0.7-cm margin should be provided on the planning target volume to the block edge to
take beam penumbra into account (Figure 1, see TEST-C 4 of 5).1
Special Considerations
• Ipsilateral pelvic surgery (eg, inguinal herniorrhaphy or orchiopexy) may alter the lymphatic drainage of the testis. As a result, irradiation of
the ipsilateral iliac and inguinal lymph nodes, including the surgical scar from prior surgery, has been advocated even in patients with stage
I cancer.8,13 Stage IIA–IIB on (TEST-C 3 of 5)
References on
Note: All recommendations are category 2A unless otherwise indicated.
Clinical Trials: NCCN believes that the best management of any patient with cancer is in a clinical trial. Participation in clinical trials is especially encouraged. TEST-C 5 of 5
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Testicular Cancer - Pure Seminoma Discussion

Stage II PRINCIPLES OF RADIOTHERAPY FOR PURE TESTICULAR SEMINOMA

• Patients should not receive primary RT if they have a horseshoe (pelvic) kidney, inflammatory bowel disease, or a history of RT.
• For patients with clinical stage IIA–B disease, treatment is delivered in two consecutive AP-PA phases (modified dog-leg fields and cone
down). There is no break between the two phases.
• Modified Dog-Leg Fields:
Dose:
◊ The initial phase consists of treatment of modified dog-leg fields to 20–25.5 Gy (see Table 1 on TEST-C 2 of 5 for dose fractionation options).
◊ Boost gross disease to achieve a total dose of approximately:
Table 2: Boost to Gross Disease
Stage Total Dose (Gy) Dose per Fraction (Gy)
IIA 30 1.8–2.0 Gy per fraction
IIB 36 1.8–2.0 Gy per fraction
Target: The fields should include the retroperitoneal and proximal ipsilateral iliac lymph nodes.
◊ Modified dog-leg fields as described by Classen et al are preferred.14
◊ Care should be taken to ensure coverage of the ipsilateral common, external, and proximal internal iliac lymph nodes down to the top of
the acetabulum.
◊ The fields can be set up using bony landmarks or by contouring the vascular structures, as for stage I.
▪ The superior border should be placed at the bottom of vertebral body T10/T11.15
▪ The inferior border should be placed at the top of the acetabulum.14
▪ The medial border for the lower aspect of the modified dog-leg fields extends from the tip of the contralateral transverse process of
the fifth lumbar vertebra toward the medial border of the ipsilateral obturator foramen.
▪ The lateral border for the lower aspect of the modified dog-leg fields is defined by a line from the tip of the ipsilateral transverse
process of the fifth lumbar vertebra to the superolateral border of the ipsilateral acetabulum.
▪ Preferably, one should contour the aorta and IVC from the bottom of the T10/T11 vertebra inferiorly and ipsilateral iliac arteries and
veins down to the top of the acetabulum. One should provide a 1.2- to 1.9-cm margin on these vascular structures for the clinical
target volume.7,11 The planning target volume is then established by uniformly expanding the clinical target volume by 0.5 cm in all
directions to account for treatment setup errors.12 A uniform 0.7-cm margin should be provided on the planning target volume to the
block edge to take beam penumbra into account (Figure 2, TEST-C 4 of 5).1
▪ It is not necessary to include the ipsilateral inguinal nodes or the inguinal scar in the AP-PA fields unless the patient has a history of
ipsilateral pelvic surgery (eg, inguinal herniorrhaphy or orchiopexy).
• Cone Down:
Dose: The second phase (cone down) of the radiotherapy consists of daily 1.8–2 Gy fractions to a cumulative total dose of approximately
30 Gy for stage IIA and 36 Gy for stage IIB.14
Target: The nodal mass (gross tumor volume) must be contoured. A uniform, 2-cm margin from the gross tumor volume to block edge
should be provided for the AP-PA cone down fields. (Figure 3, TEST-C 4 of 5). Stage I on TEST-C 2 of 5
References on TEST-C 5 of 5
Note: All recommendations are category 2A unless otherwise indicated.
Clinical Trials: NCCN believes that the best management of any patient with cancer is in a clinical trial. Participation in clinical trials is especially encouraged.
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Testicular Cancer - Pure Seminoma Discussion

PRINCIPLES OF RADIOTHERAPY FOR PURE TESTICULAR SEMINOMA

Treatment Modalities
• Linear accelerators with >6 MV photons should be used when possible.

Target Volumes by Stage (or location)

Figure 1: Figure 2: Figure 3:
Stage I RT Field Stage II RT Large Field Stage II Cone-down Field

Stage I on TEST-C 2 of 5
Stage IIA, IIB on TEST-C 3 of 5
References on TEST-C 5 of 5
Note: All recommendations are category 2A unless otherwise indicated.
Clinical Trials: NCCN believes that the best management of any patient with cancer is in a clinical trial. Participation in clinical trials is especially encouraged.
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Testicular Cancer - Pure Seminoma Discussion

PRINCIPLES OF RADIOTHERAPY FOR PURE TESTICULAR SEMINOMA

REFERENCES
1 Zilli T, Boudreau C, Doucet R, et al. Bone marrow-sparing intensity-modulated radiation therapy for Stage I seminoma. Acta Oncol 2011;50:555-562.
2 Hall EJ, Wuu CS. Radiation-induced second cancers: the impact of 3D-CRT and IMRT. Int J Radiat Oncol Biol Phys 2003;56:83-88.
3 Ragni G, Somigliana E, Restelli L, et al. Sperm banking and rate of assisted reproduction treatment: insights from a 15-year cryopreservation program
for male cancer patients. Cancer 2003;97:1624-1629.
4 Saito K, Suzuki K, Iwasaki A, et al. Sperm cryopreservation before cancer chemotherapy helps in the emotional battle against cancer. Cancer
2005;104:521-524.
5 Garmezy B, Pagliaro LC. Choosing treatment for stage I seminoma: who should get what? Oncology (Williston Park) 2009;23:753, 759.
6 Fossa SD, Horwich A, Russell JM, et al. Optimal planning target volume for stage I testicular seminoma: A Medical Research Council randomized trial.
Medical Research Council Testicular Tumor Working Group. J Clin Oncol 1999;17:1146.
7 Dinniwell R, Chan P, Czarnota G, et al. Pelvic lymph node topography for radiotherapy treatment planning from ferumoxtran-10 contrast-enhanced
magnetic resonance imaging. Int J Radiat Oncol Biol Phys 2009;74:844-851.
8 McMahon CJ, Rofsky NM, Pedrosa I. Lymphatic metastases from pelvic tumors: anatomic classification, characterization, and staging. Radiology
2010;254:31-46.
9 Bruns F, Bremer M, Meyer A, Karstens JH. Adjuvant radiotherapy in stage I seminoma: is there a role for further reduction of treatment volume? Acta
Oncol 2005;44:142-148.
10 Classen
 J, Schmidberger H, Meisner C, et al. Para-aortic irradiation for stage I testicular seminoma: results of a prospective study in 675 patients. A
trial of the German testicular cancer study group (GTCSG). Br J Cancer 2004;90:2305-2311.
11 Shih
 HA, Harisinghani M, Zietman AL, et al. Mapping of nodal disease in locally advanced prostate cancer: rethinking the clinical target volume for
pelvic nodal irradiation based on vascular rather than bony anatomy. Int J Radiat Oncol Biol Phys 2005;63:1262-1269.
12 Boujelbene N, Cosinschi A, Khanfir K, et al. Pure seminoma: a review and update. Radiat Oncol 2011;6:90.
13 Jones
 WG, Fossa SD, Mead GM, et al. Randomized trial of 30 versus 20 Gy in the adjuvant treatment of stage I Testicular Seminoma: a report on
Medical Research Council Trial TE18, European Organisation for the Research and Treatment of Cancer Trial 30942 (ISRCTN18525328). J Clin
Oncol 2005;23:1200-1208.
14 Classen
 J, Schmidberger H, Meisner C, Souchon R. Radiotherapy for stages IIA/B testicular seminoma: final report of a prospective multicenter
clinical trial. J Clin Oncol 2003;21:1101-1106.
15 Paly JJ, Efstathiou JA, Hedgire SS, et al. Mapping patterns of nodal metastases in seminoma: rethinking radiotherapy fields. Radiother Oncol
2013;106:64-68.

Note: All recommendations are category 2A unless otherwise indicated.

Clinical Trials: NCCN believes that the best management of any patient with cancer is in a clinical trial. Participation in clinical trials is especially encouraged.
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Testicular Cancer Discussion

RISK CLASSIFICATION FOR ADVANCED DISEASE

(post-orchiectomy)a,b
Risk Status Nonseminoma Seminoma
Good Risk Testicular or retroperitoneal primary Any primary site
tumorc and
and No nonpulmonary visceral metastases
No nonpulmonary visceral metastases and
and Normal AFP
Post-orchiectomy markers- all of: Any hCG
AFP < 1,000 ng/mL Any LDHd
hCG < 5,000 IU/L
LDH < 1.5 x upper limit of normal
Intermediate Testicular or retroperitoneal primary Any primary site
Risk tumorc and
and Nonpulmonary visceral metastases
No nonpulmonary visceral metastases and
and Normal AFP
Post-orchiectomy markers- any of: Any hCG
AFP 1,000–10,000 ng/mL Any LDH
hCG 5,000–50,000 IU/L
LDH 1.5–10 x upper limit of normal
Poor Risk Mediastinal primary tumorc No patients classified as poor
or prognosis
Nonpulmonary visceral metastases
or
Post-orchiectomy markers- any of:
AFP > 10,000 ng/mL
hCG > 50,000 IU/L
LDH > 10 x upper limit of normal
Source: Figure 4 from the International Germ Cell Cancer Collaborative Group: International Germ Cell
Consensus Classification: A Prognostic Factor-Based Staging System for Metastatic Germ Cell Cancers. J Clin
Oncol 1997;15:594-603. Reprinted with permission of the American Society of Clinical Oncology.
a Markers used for risk classification are post-orchiectomy.
b Newer risk model to give prognostic information can be used through nomogram: https://eortc.shinyapps.io/IGCCCG-Update/ (Gillessen S, et al. J Clin Oncol
2021;39:1563-1574).
c Referral to a high-volume center is recommended for patients with extragonadal germ cell tumors. See Discussion.
d Patients with good-risk disseminated seminoma with an LDH >2.5 x ULN have a worse prognosis than other good-risk patients. However, there are insufficient data at
this time to recommend treating these patients differently based on LDH.

Note: All recommendations are category 2A unless otherwise indicated.

Clinical Trials: NCCN believes that the best management of any patient with cancer is in a clinical trial. Participation in clinical trials is especially encouraged.

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Testicular Cancer Discussion

FIRST-LINE CHEMOTHERAPY REGIMENS FOR GERM CELL TUMORS

Preferred Regimens
• BEP
Etoposide 100 mg/m2 IV on Days 1–5
Cisplatin 20 mg/m2 IV on Days 1–5
Bleomycin 30 units IV weekly on Days 1, 8, and 15 or Days 2, 9, and 16
Repeat every 21 days1

• EP
(Option only for patients with good-risk [TEST-D], patients with pathologic stage II disease, and patients with viable germ cell tumor at
surgery following first-line chemotherapy)
Etoposide 100 mg/m2 IV on Days 1–5
Cisplatin 20 mg/m2 IV on Days 1–5
Repeat every 21 days2

Other Recommended Regimens

• VIP3
(For patients with intermediate or poor risk disease or patients with viable germ cell tumor at surgery following first-line chemotherapy
[SEM-4 and NSEM-6])
Etoposide 75 mg/m2 IV on Days 1–5
Ifosfamide 1200 mg/m2 on Days 1–5 with mesna protection
Cisplatin 20 mg/m2 IV on Days 1–5
Repeat every 21 days4

1 Saxman SB, Finch D, Gonin R, Einhorn LH. Long-term follow-up of a phase III study of three versus four cycles of bleomycin, etoposide, and cisplatin in favorable-
prognosis germ-cell tumors: The Indiana University Experience. J Clin Oncol 1998;16:702-706.
2 Xiao H, Mazumdar M, Bajorin DF, et al. Long-term follow-up of patients with good-risk germ cell tumors treated with etoposide and cisplatin. J Clin Oncol 1997;15:2553-
2558.
3 VIP: This regimen is high risk for febrile neutropenia and granulocyte colony-stimulating factors (G-CSFs) should be used (See NCCN Guidelines for Hematopoietic
Growth Factors).
4 Nichols CR, Catalano PJ, Crawford ED, et al. Randomized comparison of cisplatin and etoposide and either bleomycin or ifosfamide in treatment of advanced
disseminated germ cell tumors: An Eastern Cooperative Oncology Group, Southwest Oncology Group, and Cancer and Leukemia Group B Study. J Clin Oncol
1998;16:1287-1293.

Note: All recommendations are category 2A unless otherwise indicated.

Clinical Trials: NCCN believes that the best management of any patient with cancer is in a clinical trial. Participation in clinical trials is especially encouraged.

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Testicular Cancer Discussion

SECOND-LINE CHEMOTHERAPY REGIMENS FOR METASTATIC GERM CELL TUMORS

Conventional-Dose Chemotherapy Regimens High-Dose Chemotherapy Regimens

Preferred Regimens Preferred Regimens

• TIP1 • Carboplatin/etoposide
Paclitaxel 250 mg/m2 IV on Day 1 Carboplatin 700 mg/m2/day (body surface area) IV administered on days -5,
Ifosfamide 1500 mg/m2 IV on Days 2–5 with mesna protection -4, -3
Cisplatin 25 mg/m2 IV on Days 2–5 Etoposide 750 mg/m2/day IV administered on days -5, -4, -3
Repeat every 21 days2 Administer days -5, -4, and -3 before peripheral blood stem cell infusion for
2 cycles4
• VeIP1
Vinblastine 0.11 mg/kg IV Push on Days 1–2 • Paclitaxel/ifosfamide/carboplatin/etoposide
Ifosfamide 1200 mg/m2 IV on Days 1–5 with mesna protection Paclitaxel 200 mg/m2 IV over 24 hours on Day 1
Cisplatin 20 mg/m2 IV on Days 1–5 Ifosfamide 2000 mg/m2 over 4 hours with mesna protection on Days 2–4
Repeat every 21 days3 Repeat every 14 days for 2 cycles followed by
Carboplatin AUC 7–8 IV over 60 minutes on Days 1–3
Etoposide 400 mg/m2 IV on Days 1–3
Administer with peripheral blood stem cell support at 14- to 21-day
intervals for 3 cycles5

1 TIP, VeIP: These regimens are high risk for febrile neutropenia and G-CSFs should be used (See NCCN Guidelines for Hematopoietic Growth Factors).
2 Kondagunta GV, Bacik J, Donadio A, et al. Combination of paclitaxel, ifosfamide, and cisplatin is an effective second-line therapy for patients with relapsed testicular
germ cell tumors. J Clin Oncol 2005;23:6549-6555.
3 Loehrer PJ Sr, Lauer R, Roth BJ, et al. Salvage therapy in recurrent germ cell cancer: ifosfamide and cisplatin plus either vinblastine or etoposide. Ann Intern Med
1988;109:540-546.
4 Einhorn LH, Williams SD, Chamness A, et al. High-dose chemotherapy and stem-cell rescue for metastatic germ-cell tumors. N Engl J Med 2007;357:340-348.
5 Feldman DR, Sheinfeld J, Bajorin DF, et al. TI-CE high-dose chemotherapy for patients with previously treated germ cell tumors: results and prognostic factor analysis.
J Clin Oncol 2010;28:1706-1713.

Note: All recommendations are category 2A unless otherwise indicated.

Clinical Trials: NCCN believes that the best management of any patient with cancer is in a clinical trial. Participation in clinical trials is especially encouraged.

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Testicular Cancer Discussion

THIRD-LINE CHEMOTHERAPY REGIMENS FOR METASTATIC GERM CELL TUMORSa

High-Dose Chemotherapy NOT Previously Received
Preferred Regimens (High-Dose Chemotherapy)
• Carboplatin/etoposide
Carboplatin 700 mg/m2/day (body surface area) IV administered on days -5, -4, -3
Etoposide 750 mg/m2/day IV administered on days -5, -4, -3
Administered days -5, -4, and -3 before peripheral blood stem cell infusion for 2 cycles1
• Paclitaxel/ifosfamide/carboplatin/etoposide
Paclitaxel 200 mg/m2 IV over 24 hours on Day 1
Ifosfamide 2000 mg/m2 over 4 hours with mesna protection on Days 2–4
Repeat every 14 days for 2 cycles followed by
Carboplatin AUC 7–8 IV over 60 minutes on Days 1–3
Etoposide 400 mg/m2 IV on Days 1–3
Administered with peripheral blood stem cell support at 14- to 21-day intervals for 3 cycles2
Other Recommended Regimens
• Gemcitabine/paclitaxel/oxaliplatin3
Gemcitabine 800 mg/m2 IV over 30 minutes on Days 1 and 8
Paclitaxel 80 mg/m2 IV over 60 minutes on Days 1 and 8
Oxaliplatin 130 mg/m2 IV over 2 hours on Day 1
Administered on a 21-day cycle for 8 cycles
• Gemcitabine/oxaliplatin4-6
Gemcitabine 1000–1250 mg/m2 IV over 30 minutes on Days 1 and 8
followed by
Oxaliplatin 130 mg/m2 IV over 2 hours on Day 1
Administered on a 21-day cycle until disease progression or unacceptable toxicity
• Gemcitabine/paclitaxel7,8
Gemcitabine 1000 mg/m2 IV over 30 minutes on Days 1, 8, and 15
Paclitaxel 100 mg/m2 IV over 60 minutes on Days 1, 8, and 15
Administered on a 28-day cycle for 6 cycles
• Etoposide (oral)9
Etoposide 50–100 mg PO daily on Days 1–21
Administered on a 28-day cycle until disease progression or unacceptable toxicity
Useful in Certain Circumstances
• Pembrolizumab (for microsatellite instability-high [MSI-H]/mismatch repair deficient [dMMR] or tumor mutational burden-high [TMB-H]
tumors)b,10,11,12
Pembrolizumab 200 mg IV over 30 minutes on Day 1
Administered on a 21-day cycle until disease progression or unacceptable toxicity or up to 24 months
Pembrolizumab 400 mg IV over 30 minutes on Day 1
Administered on a 42-day cycle until disease progression or unacceptable toxicity or up to 24 months13
a IfVeIP or TIP received as second-line therapy, high-dose b Tumor mutational burden-high (TMB-H) [≥10 mutations/megabase (mut/Mb)] tumors, as determined
chemotherapy is the preferred third-line option. by a validated and/or FDA-approved comprehensive genomic profiling (CGP) assay.

Note: All recommendations are category 2A unless otherwise indicated. References

Clinical Trials: NCCN believes that the best management of any patient with cancer is in a clinical trial. Participation in clinical trials is especially encouraged.
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Testicular Cancer Discussion

THIRD-LINE CHEMOTHERAPY REGIMENS FOR METASTATIC GERM CELL TUMORSa

High-Dose Chemotherapy Previously Received

Preferred Regimens
• Gemcitabine/paclitaxel/oxaliplatin3
Gemcitabine 800 mg/m2 IV over 30 minutes on Days 1 and 8
Paclitaxel 80 mg/m2 IV over 60 minutes on Days 1 and 8
Oxaliplatin 130 mg/m2 IV over 2 hours on Day 1
Administered on a 21-day cycle for 8 cycles
• Gemcitabine/oxaliplatin4-6
Gemcitabine 1000–1250 mg/m2 IV over 30 minutes on Days 1 and 8
followed by
Oxaliplatin 130 mg/m2 IV over 2 hours on Day 1
Administered on a 21-day cycle until disease progression or unacceptable toxicity
• Gemcitabine/paclitaxel7,8
Gemcitabine 1000 mg/m2 IV over 30 minutes on Days 1, 8, and 15
Paclitaxel 100 mg/m2 IV over 60 minutes on Days 1, 8, and 15
Administered on a 28-day cycle for 6 cycles
• Etoposide (oral)9
Etoposide 50–100 mg PO daily on Days 1–21
Administered on a 28-day cycle until disease progression or unacceptable toxicity

Useful in Certain Circumstances

• Pembrolizumab (for MSI-H/dMMR or TMB-H tumors)b,10,11,12,13
Pembrolizumab 200 mg IV over 30 minutes on Day 1
Administered on a 21-day cycle until disease progression or unacceptable toxicity or up to 24 months
Pembrolizumab 400 mg IV over 30 minutes on Day 1
Administered on a 42-day cycle until disease progression or unacceptable toxicity or up to 24 months14

a If VeIP or TIP received as second-line therapy, high-dose chemotherapy is the preferred third-line option.
b TMB-H (≥10 mut/Mb) tumors, as determined by a validated and/or FDA-approved CGP assay.

Note: All recommendations are category 2A unless otherwise indicated. References

Clinical Trials: NCCN believes that the best management of any patient with cancer is in a clinical trial. Participation in clinical trials is especially encouraged.
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Testicular Cancer Discussion

THIRD-LINE CHEMOTHERAPY REGIMENS FOR METASTATIC GERM CELL TUMORS

REFERENCES
1 Einhorn
 LH, Williams SD, Chamness A, et al. High-dose chemotherapy and stem-cell rescue for metastatic germ-cell tumors. N Engl J Med
2007;357:340-348.
2 Feldman
 DR, Sheinfeld J, Bajorin DF, et al. TI-CE high-dose chemotherapy for patients with previously treated germ cell tumors: results and prognostic
factor analysis. J Clin Oncol 2010;28:1706-1713.
3 Bokemeyer
 C, Oechsle K, Honecker F, et al; German Testicular Cancer Study Group. Combination chemotherapy with gemcitabine, oxaliplatin, and
paclitaxel in patients with cisplatin-refractory or multiply relapsed germ-cell tumors: A study of the German Testicular Cancer Study Group. Ann Oncol
2008;19:448-453.
4 Pectasides
 D, Pectasides M, Farmakis D, et al. Gemcitabine and oxaliplatin (GEMOX) in patients with cisplatin-refractory germ cell tumors: a phase II
study. Ann Oncol 2004;15:493-497.
5 Kollmannsberger
 C, Beyer J, Liersch R, et al. Combination chemotherapy with gemcitabine plus oxaliplatin in patients with intensively pretreated or
refractory germ cell cancer: a study of the German Testicular Cancer Study Group. J Clin Oncol 2004;22:108-114.
6 De
 Giorgi U, Rosti G, Aieta M, et al. Phase II study of oxaliplatin and gemcitabine salvage chemotherapy in patients with cisplatin-refractory
nonseminomatous germ cell tumor. Eur Urol 2006;50:1032-1038.
7 Einhorn
 LH, Brames MJ, Juliar B, Williams SD. Phase II study of paclitaxel plus gemcitabine salvage chemotherapy for germ cell tumors after
progression following high-dose chemotherapy with tandem transplant. J Clin Oncol 2007;25:513-516.
8 Mulherin
 BP, Brames MJ, Einhorn LH. Long-term survival with paclitaxel and gemcitabine for germ cell tumors after progression following high-dose
chemotherapy with tandem transplant. Am J Clin Oncol 2015;38:373-376.
9 Miller
 JC, Einhorn LH. Phase II study of daily oral etoposide in refractory germ cell tumors. Semin Oncol 1990;17:36-39.
10 Le DT, Durham JN, Smith KN, et al. Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. Science 2017;357:409-413.
11 Le DT, Uram JN, Wang H, et al. PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med 2015;372:2509-2520.
12 Marabelle A, Fakih M, Lopez J, et al. Association of tumour mutational burden with outcomes in patients with advanced solid tumours treated with
pembrolizumab: prospective biomarker analysis of the multicohort, open-label, phase 2 KEYNOTE-158 study. Lancet Oncol 2020;21:1353-1365.
13Marabelle A, Le DT, Ascierto PA, et al. Efficacy of pembrolizumab in patients with noncolorectal high microsatellite instability/mismatch repair-deficient
cancer: Results from the phase II KEYNOTE-158 Study. J Clin Oncol 2020;38:1-10.
14 Lala M, Li TR, de Alwis DP, et al. A six-weekly dosing schedule for pembrolizumab in patients with cancer based on evaluation using modelling and
simulation. Eur J Cancer 2020;131:68-75.

Note: All recommendations are category 2A unless otherwise indicated.

Clinical Trials: NCCN believes that the best management of any patient with cancer is in a clinical trial. Participation in clinical trials is especially encouraged.
TEST-G
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PRINCIPLES OF SURGERY FOR GERM CELL TUMORS

• Radical inguinal orchiectomy is the gold standard for the diagnosis and initial management of a suspected testicular cancer. Trans-scrotal
orchiectomy is discouraged as scrotal violation is associated with higher rates of local recurrence and altered pathways of metastatic
dissemination.
When a patient presents with a testicular mass, rapidly increasing beta-hCG or AFP, metastatic disease on imaging, and symptoms related
to disseminated disease, chemotherapy can be initiated immediately without waiting for orchiectomy or a biopsy-proven histologic
diagnosis. However, radical inguinal orchiectomy should be performed at completion of chemotherapy.

• Nerve-sparing and/or template dissection approach to minimize the risk of ejaculatory disorders should be considered in patients
undergoing primary RPLND for stage I nonseminoma.

• The “split and roll” technique in which lumbar vessels are identified and sequentially ligated allows resection of all lymphatic tissue around
and behind the great vessels (ie, aorta, IVC) and minimizes the risk of an in-field recurrence.

Testis-Sparing Surgery (TSS)

• TSS, such as partial orchiectomy, can be considered in select patients with a testicular mass.
Indications for TSS:
◊ Synchronous bilateral germ cell tumors, a solitary testicle with a mass suspicious for germ cell tumor, or a functionally solitary testicle
with adequate gonadal function with respect to androgen production or sperm production (eg, history of contralateral testicular atrophy).
These patients should be counseled regarding the following:
– High risk of local recurrence with TSS
– Need for continued surveillance with testicular self-exam, physical exam by a physician, and/or ultrasound
– Role of adjuvant radiation to reduce the risk of local recurrence
– Impact of radiation therapy on sperm and testosterone production
– Risk of testicular atrophy, need for testosterone replacement, and/or infertility
Principles of TSS:
◊ TSS should be performed through an inguinal approach.
◊ Frozen section should be performed at the time of surgery by an experienced genitourinary pathologist.
◊ Radical orchiectomy in the setting of a normal contralateral testicle is recommended if biopsy shows testicular cancer is present or there
is suspicion of cancer.

Note: All recommendations are category 2A unless otherwise indicated.

Clinical Trials: NCCN believes that the best management of any patient with cancer is in a clinical trial. Participation in clinical trials is especially encouraged.
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PRINCIPLES OF SURGERY FOR GERM CELL TUMORS

Retroperitoneal Lymph Node Dissection (RPLND)
• A template dissection or a nerve-sparing approach to minimize the risk of ejaculatory disorders should be considered in patients
undergoing primary RPLND for stage I nonseminoma.

• The “split and roll” technique in which lumbar vessels are identified and sequentially ligated allows resection of all lymphatic tissue around
and behind the great vessels (ie, aorta, IVC) and minimizes the risk of an in-field recurrence.

• Referral to high-volume centers should be considered for RPLND.

• Minimally invasive laparoscopic or robotic approaches to RPLND have limited long-term data and relatively high adjuvant chemotherapy
use. Therefore, minimally invasive RPLND is not recommended as standard management, but can be considered in highly selected cases at
high-volume centers.

Postchemotherapy Setting
• Postchemotherapy RPLND is indicated in patients with metastatic NSGCT with a residual retroperitoneal mass following systemic
chemotherapy and normalized postchemotherapy serum tumor markers.

• A full bilateral template RPLND should be performed in all patients undergoing RPLND in the postchemotherapy setting, with the
boundaries of dissection being the renal hilar vessels (superiorly), ureters (laterally), and the common iliac arteries (inferiorly)
Completeness of resection is a consistent independent predictor of clinical outcome. In postchemotherapy RPLND, surgical margins should
not be compromised in an attempt to preserve ejaculation. Additional procedures and resection of adjacent structures may be required.
Modified template RPLND may be an option in select patients with initial stage IIA/B disease within the primary landing zones.

• Completeness of resection is a consistent independent predictor of clinical outcome. In postchemotherapy RPLND, surgical margins should
not be compromised in an attempt to preserve ejaculation. Additional procedures and resection of adjacent structures may be required.

Note: All recommendations are category 2A unless otherwise indicated.

Clinical Trials: NCCN believes that the best management of any patient with cancer is in a clinical trial. Participation in clinical trials is especially encouraged.
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PRINCIPLES OF IMAGING
Staging
Pure Seminoma and Nonseminoma
• Abdomen/pelvis CT scan with contrast and chest x-ray or CT scan or abdomen/pelvis MRI with and without contrast is recommended within 4
weeks prior to the initiation of chemotherapy, RPLND, or RT to confirm staging, even if scan was performed previously. (SEM-2 and NSEM-2)
Chest CT should be performed if abdomen/pelvis CT or chest x-ray is abnormal.

Treatment Response Assessment

Pure Seminoma
• Consider FDG-PET/CT scan (skull base to mid-thigh) for a residual mass >3 cm post primary chemotherapy. (SEM-4)
• FDG-PET/CT scan should be performed at least 6 weeks following completion of chemotherapy.
A negative FDG-PET/CT following chemotherapy is very reassuring. If FDG-PET/CT scan is positive, resection or interventional radiology-
guided biopsy should be considered. An alternative is to wait an additional 8–12 weeks and repeat FDG-PET/CT scan to assess for changes.
If the mass is persistently FDG-avid on PET, then resection or biopsy is recommended.

Surveillance
Pure Seminoma and Nonseminoma (TEST-A and TEST-B)
• MRI with and without contrast can be considered in place of an abdomen/pelvis CT.
MRI protocol should include visualization of retroperitoneal and pelvic nodes.
• Use the same imaging modality (CT or MRI) throughout surveillance.
• In stage I seminoma and nonseminoma, chest x-rays should be obtained when abdomen/pelvis CT scans are performed. Additional chest
imaging is not indicated under normal circumstances. In a retrospective review of nearly 560 patients, 76 patients relapsed with only four
patients having disease in the chest, one of whom had an abnormal chest x-ray (but also in the setting of an elevated AFP).1 Similar data from
Daugaard et al showed no role for chest x-ray in detecting relapse.2 Other series have also called into question the value of chest x-rays in
this and other surveillance settings for germ cell tumors.3,4

1 De La Pena H, Sharma A, Glicksman C, et al. No longer any role for routine follow-up chest x-rays in men with stage I germ cell cancer. Eur J Cancer 2017;84:354-
359.
2 Daugaard G, Gundgaard MG, Mortensen MS, et al. Surveillance for stage I nonseminoma testicular cancer: outcomes and long-term follow-up in a population-based
cohort. J Clin Oncol 2014;32:3817-3823.
3 Tolan S, Vesprini D, Jewett MA, et al. No role for routine chest radiography in stage I seminoma surveillance. Eur Urol 2010;57:474-479.
4 Gietema JA, Meinardi MT, Sleijfer DT, et al. Routine chest X-rays have no additional value in the detection of relapse during routine follow-up of patients treated with
chemotherapy for disseminated non-seminomatous testicular cancer. Ann Oncol 2002;13:1616-1620.

Note: All recommendations are category 2A unless otherwise indicated.

Clinical Trials: NCCN believes that the best management of any patient with cancer is in a clinical trial. Participation in clinical trials is especially encouraged.

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American Joint Committee on Cancer (AJCC)

TNM Staging Classification for Testis Cancer 8th ed., 2017

Table 1. Definitions for T, N, M

Clinical T Primary Tumor
cTX Primary tumor cannot be assessed
cT0 No evidence of primary tumor
cTis Germ cell neoplasia in situ
cT4 Tumor invades scrotum with or without vascular/lymphatic invasion
Note: Except for Tis confirmed by biopsy and T4, the extent of the primary tumor is classified
by radical orchiectomy. TX may be used for other categories for clinical staging.

Pathological T Primary Tumor

pTX Primary tumor cannot be assessed
pT0 No evidence of primary tumor
pTis Germ cell neoplasia in situ
pT1 Tumor limited to testis (including rete testis invasion) without lymphovascular invasion
pT1a* Tumor smaller than 3 cm in size
pT1b* Tumor 3 cm or larger in size
pT2 Tumor limited to testis (including rete testis invasion) with lymphovascular invasion
OR
Tumor invading hilar soft tissue or epididymis or penetrating visceral mesothelial layer
covering the external surface of tunica albuginea with or without lymphovascular invasion
pT3 Tumor directly invades spermatic cord soft tissue with or without lymphovascular invasion
pT4 Tumor invades scrotum with or without lymphovascular invasion

*Subclassification of pT1 applies to only pure seminoma.

Continued

Used with permission of the American College of Surgeons, Chicago, Illinois. The original source for this information is the AJCC Cancer Staging Manual, Eighth Edition
(2017) published by Springer International Publishing.

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American Joint Committee on Cancer (AJCC)

TNM Staging Classification for Testis Cancer 8th ed., 2017

Table 1 (continued)
Clinical N Regional Lymph Nodes M Distant Metastasis
cNX Regional lymph nodes cannot be assessed M0 No distant metastases
cN0 No regional lymph node metastasis M1 Distant metastases
cN1 Metastasis with a lymph node mass 2 cm or smaller in greatest M1a Non-retroperitoneal nodal or pulmonary metastases
dimension
OR M1b Non-pulmonary visceral metastases
Multiple lymph nodes, none larger than 2 cm in greatest
dimension
cN2 Metastasis with a lymph node mass larger than 2 cm but not S Serum Markers
larger than 5 cm in greatest dimension SX Marker studies not available or not performed
OR
Multiple lymph nodes, any one mass larger than 2 cm but not S0 Marker study levels within normal limits
larger than 5 cm in greatest dimension S1 LDH <1.5 x N* and hCG (mIU/mL) <5,000
cN3 Metastasis with a lymph node mass larger than 5 cm in and AFP (ng/mL) <1,000
greatest dimension S2 LDH 1.5–10 x N* or hCG (mIU/mL) 5,000–50,000
or AFP (ng/mL) 1,000–10,000
S3 LDH >10 x N* or hCG (mIU/mL) >50,000
Pathological N Regional Lymph Nodes or AFP (ng/mL) >10,000
pNX Regional lymph nodes cannot be assessed
pN0 No regional lymph node metastasis
pN1 Metastasis with a lymph node mass 2 cm or smaller in
greatest dimension and less than or equal to five nodes
positive, none larger than 2 cm in greatest dimension
pN2 Metastasis with a lymph node mass larger than 2 cm but
not larger than 5 cm in greatest dimension; or more than
five nodes positive, none larger than 5 cm; or evidence of
extranodal extension of tumor
pN3 Metastasis with a lymph node mass larger than 5 cm in
greatest dimension
Continued
* N indicates the upper limit of normal for the LDH assay.
Used with permission of the American College of Surgeons, Chicago, Illinois. The original source for this information is the AJCC Cancer Staging Manual, Eighth Edition
(2017) published by Springer International Publishing.

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American Joint Committee on Cancer (AJCC)

TNM Staging Classification for Testis Cancer 8th ed., 2017

Table 2. AJCC Prognostic Stage Groups Histologic Grade (G)

T N M S • Germ cell tumors are not graded
Stage 0 pTis N0 M0 S0
Stage I pT1-T4 N0 M0 SX
Stage IA pT1 N0 M0 S0
Stage IB pT2 N0 M0 S0
pT3 N0 M0 S0
pT4 N0 M0 S0
Stage IS Any pT/TX N0 M0 S1-3
Stage II Any pT/TX N1-3 M0 SX
Stage IIA Any pT/TX N1 M0 S0
Any pT/TX N1 M0 S1
Stage IIB Any pT/TX N2 M0 S0
Any pT/TX N2 M0 S1
Stage IIC Any pT/TX N3 M0 S0
Any pT/TX N3 M0 S1
Stage III Any pT/TX Any N M1 SX
Stage IIIA Any pT/TX Any N M1a S0
Any pT/TX Any N M1a S1
Stage IIIB Any pT/TX N1-3 M0 S2
Any pT/TX Any N M1a S2
Stage IIIC Any pT/TX N1-3 M0 S3
Any pT/TX Any N M1a S3
Any pT/TX Any N M1b Any S

Used with permission of the American College of Surgeons, Chicago, Illinois. The original source for this information is the AJCC Cancer Staging Manual, Eighth Edition
(2017) published by Springer International Publishing.

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ABBREVIATIONS

3D-CRT three-dimensional conformal radiation therapy

AFP alpha-fetoprotein
AP-PA anteroposterior-posteroanterior
AUC area under the curve
beta-hCG beta-human chorionic gonadotropin
CGP comprehensive genomic profiling
dMMR mismatch repair deficient
D50% dose delivered to 50% of the volume
GFR glomerular filtration rate
G-CSFs granulocyte colony-stimulating factors
H&P history and physical
hCG human chorionic gonadotropin
IMRT intensity-modulated radiation therapy
IVC inferior vena cava
LDH lactate dehydrogenase
MMR mismatch repair
MSI microsatellite instability
MSI-H microsatellite instability-high
mut/Mb mutations/megabase
NSGCT nonseminomatous germ cell tumor
RPLND retroperitoneal lymph node dissection
TMB tumor mutational burden
TMB-H tumor mutational burden-high
TSS testis sparing surgery
ULN upper limit of normal

ABBR-1
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NCCN Categories of Evidence and Consensus

Category 1 Based upon high-level evidence, there is uniform NCCN consensus that the intervention is appropriate.
Category 2A Based upon lower-level evidence, there is uniform NCCN consensus that the intervention is appropriate.
Category 2B Based upon lower-level evidence, there is NCCN consensus that the intervention is appropriate.
Category 3 Based upon any level of evidence, there is major NCCN disagreement that the intervention is appropriate.
All recommendations are category 2A unless otherwise indicated.

NCCN Categories of Preference

Interventions that are based on superior efficacy, safety, and evidence; and, when appropriate,
Preferred intervention affordability.
Other recommended Other interventions that may be somewhat less efficacious, more toxic, or based on less mature data;
intervention or significantly less affordable for similar outcomes.
Useful in certain
Other interventions that may be used for selected patient populations (defined with recommendation).
circumstances
All recommendations are considered appropriate.

Note: All recommendations are category 2A unless otherwise indicated.

Clinical Trials: NCCN believes that the best management of any patient with cancer is in a clinical trial. Participation in clinical trials is especially encouraged.

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Discussion This discussion corresponds to the NCCN Guidelines for Nonseminoma Stage IS ............................................................. MS-19
Testicular Cancer. Last updated on October 29, 2024.
Nonseminoma Stage IIA ............................................................ MS-20
Table of Contents
Nonseminoma Stage IIB ............................................................ MS-21
Overview ........................................................................................... MS-2
Advanced Metastatic Nonseminoma .......................................... MS-22
Guidelines Update Methodology ..................................................... MS-3
Second-Line and Subsequent Therapy for Metastatic Germ Cell
Literature Search Criteria................................................................. MS-3 Tumors ............................................................................................ MS-24

Sensitive/Inclusive Language Usage .............................................. MS-4 Second-Line Therapy ................................................................ MS-24

Clinical Presentation, Workup, and Primary Treatment................. MS-4 Third-Line Therapy .................................................................... MS-25

Clinical Presentation .................................................................... MS-4 Treatment of Brain Metastases ..................................................... MS-26

Workup ........................................................................................ MS-4 Malignant Transformation of Teratoma ........................................ MS-27

Primary Treatment ....................................................................... MS-4 Summary......................................................................................... MS-27

Staging .............................................................................................. MS-5 References ...................................................................................... MS-29

Risk Classification for Advanced Disease ..................................... MS-7

Pure Seminoma ................................................................................ MS-7

Pure Seminoma Stages IA and IB ................................................ MS-8

Pure Seminoma Stage IS ........................................................... MS-12

Pure Seminoma Stages IIA and IIB ............................................ MS-12

Pure Seminoma Stages IIC and III ............................................. MS-14

Nonseminoma................................................................................. MS-16

Nonseminoma Stage I Without Risk Factors ............................... MS-17

Nonseminoma Stage I With Risk Factors.................................... MS-18

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used to aid in determining prognosis of metastatic germ cell tumors. AFP

Overview
and beta-hCG are also used for assessing treatment outcomes. For risk
Testicular cancer accounts for <1% of new cancer cases with a majority of stratification, levels of AFP, beta-hCG and LDH should all be measured on
patients being diagnosed between the ages of 20 and 34 years.1,2 The day 1 of cycle one of first-line chemotherapy. In addition, levels of AFP
global incidence of this disease has been steadily rising over the past and beta-hCG should be determined before and after treatment and
several decades with an estimated 9760 new cases of testicular cancer throughout the follow-up period. Elevated markers after orchiectomy may
projected to be diagnosed in the United States in 2024.1,3-9 An estimated be the first or only indication of occult metastatic disease (ie, in patients
500 deaths will occur from testicular cancer in the United States in 2024, with stage IS disease), and elevated marker levels are often the earliest
reflecting the excellent 5-year relative survival rate for this disease sign of relapse after treatment or during surveillance. LDH is not generally
(~95%).2,10 Several risk factors for testicular cancer have been identified, used to monitor for relapse or response to treatment because false
including personal or family history of testicular cancer and positive elevations are common, but it is useful for risk stratification when
cryptorchidism.3,11,12 starting first-line chemotherapy. When interpreting marker levels, caution
should be taken when mild elevation of only one marker is observed due
Testicular germ cell tumors (GCTs) comprise 95% of malignant tumors
to the occurrence of false positives.
arising in the testes and are broadly categorized into two main histologic
subtypes: seminoma and nonseminoma.3,13,14 Seminomas and AFP is most associated with yolk sac tumors but can also be elevated in
nonseminomas typically occur at about the same rate, but nonseminomas patients with embryonal carcinoma or teratoma. Seminomas do not
tend to be more aggressive and often include multiple cell types. When produce AFP, thus, an elevated serum AFP can be diagnostic of a mixed
both seminoma and elements of nonseminoma are present, management germ cell tumor (nonseminoma) in patients whose histology has been read
follows that of a nonseminoma. The four types of nonseminomas are as pure seminoma.17-20 Therefore, the diagnosis of a seminoma is
embryonal carcinoma, choriocarcinoma, yolk sac tumor, and teratoma.13 restricted to pure seminoma histology and normal serum AFP levels.
Most nonseminomas are mixed tumors of these four subtypes. Teratomas However, mildly elevated, non-rising levels of AFP do not always indicate
can be classified as either mature or immature, but this does not affect the presence of a GCT as a small number of people have a chronically
treatment in these patients. Rarely, a teratoma may contain elements of a elevated serum AFP level and clinicians should be cautious in interpreting
somatic cancer, such as a sarcoma or adenocarcinoma, and is then mildly elevated but stable AFP.21 In general, AFP levels <30 ng/mL should
referred to as a teratoma with somatic-type malignancy. Teratomas with not be assumed to be related to a GCT in a patient and should not be the
somatic-type malignancy are managed differently from other GCTs. sole basis for decisions about treatment. If an elevation of serum AFP is
Prepubertal teratomas, which are biologically different from the much more due to a metastatic nonseminomatous GCT, then the AFP typically will be
common post-pubertal teratomas, are occasionally diagnosed in adults steadily rising. In addition, other tumors such as hepatocellular carcinomas
and are less aggressive and managed differently.15,16 and gastric carcinomas can cause AFP elevation.
The serum tumor markers alpha-fetoprotein (AFP), beta-human chorionic Beta-hCG is the most commonly elevated serum tumor marker in
gonadotropin (beta-hCG), and lactate dehydrogenase (LDH) are currently testicular cancer. Elevated serum concentrations of beta-hCG may be

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present with both seminomatous and nonseminomatous tumors. However, Together, these guidelines pertain to all stages of testicular GCTs and
in patients with seminoma with beta-hCG levels >1000 IU/L, the possibility should be closely followed to maximize the potential for cure and to avoid
of nonseminoma should be considered and the surgical specimen with unnecessary side effects, complications, and late toxicities. It is important
pathology should be re-reviewed. Referral to a high-volume center to note that pediatric GCTs are managed differently from adult GCTs and
experienced in the treatment of these patients is encouraged. Additionally, are not covered in these guidelines. Testicular tumors arising from the
patients with post-orchiectomy beta-hCG levels >5000 IU/L should receive stroma are also not covered in these guidelines as they account for <5%
a brain MRI since they are at an increased risk of having brain of cases and have a different biology and natural history.
metastases. Further workup should be considered before initiating
treatment for mildly elevated beta-hCG (generally <20 IU/L), since other Guidelines Update Methodology
factors such as hypogonadism, hyperthyroidism, and marijuana use can
The complete details of the development and update of the NCCN
cause elevations of beta-hCG.22-24 Intramuscular injection of 300 mg of
Guidelines are available at www.NCCN.org.
testosterone cypionate may be administered in cases of mild beta-hCG
elevations of unclear etiology to exclude hypogonadism as a cause. Literature Search Criteria
Elevated beta-hCG has also been reported in other tumors, such as
lymphoma, bladder cancer, and adenocarcinomas, and is thus not specific Prior to the update of this version of the NCCN Clinical Practice Guidelines
for GCTs.25 Additionally, heterophile antibodies have been reported to in Oncology (NCCN Guidelines®) for Testicular Cancer, an electronic
result in substantially elevated false-positive beta-hCG results (>400 IU/L); search of the PubMed database was performed using the following search
therefore, clinicians should consider repeating the test using a different terms: ‘testicular cancer’ and ‘germ cell tumor.’ The PubMed database
assay if a false positive is suspected due to the absence of radiographic was chosen as it remains the most widely used resource for medical
evidence of disease.26-28 literature and indexes peer-reviewed biomedical literature.

LDH is important for determining prognosis and is used to help risk stratify The search results were narrowed by selecting studies in humans
patients starting first-line chemotherapy for disseminated published in English. Results were confined to the following article types:
nonseminomatous tumors.19 There are also data indicating that in patients Clinical Trial, Phase II; Clinical Trial, Phase III; Clinical Trial, Phase IV;
receiving chemotherapy for stage II or III seminoma, an elevation of LDH Guideline; Randomized Controlled Trial; Meta-Analysis; Systematic
>2.5 times the upper limit of normal is an adverse prognostic sign in Reviews; and Validation Studies.
patients with otherwise good-risk disease.29 While serum LDH The data from key PubMed articles as well as articles from additional
concentrations are elevated in approximately 50% of patients with sources deemed as relevant to these Guidelines and/or discussed by the
advanced testicular cancer, LDH is a less specific marker for testicular Panel have been included in this version of the Discussion section (eg, e-
cancer compared to AFP and beta-hCG. Therefore, decisions regarding publications ahead of print, meeting abstracts). Any recommendations for
treatment should not be made based on mildly elevated (<2.5 × upper limit which high-level evidence is lacking are based on the Panel’s review of
of normal [ULN]) LDH alone. lower-level evidence and expert opinion.

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Workup
Sensitive/Inclusive Language Usage
If testicular cancer is being considered as a possibility, then a transscrotal
NCCN Guidelines strive to use language that advances the goals of
ultrasound with Doppler should be performed. Testicular ultrasound can
equity, inclusion, and representation. NCCN Guidelines endeavor to use
confirm the presence of a testicular mass, determine whether a mass is
language that is person-first; not stigmatizing; anti-racist, anti-classist, anti-
intra- or extratesticular, and explore the contralateral testis.30 Testicular
misogynist, anti-ageist, anti-ableist, and anti-fat-biased; and inclusive of
GCTs are typically heterogeneous, hypoechoic, and vascular on
individuals of all sexual orientations and gender identities. NCCN
ultrasound. If the ultrasound findings show a mass suspicious for
Guidelines incorporate non-gendered language, instead focusing on
malignancy, then a radical inguinal orchiectomy is generally performed to
organ-specific recommendations. This language is both more accurate
make a diagnosis. Testis-sparing surgery (ie, partial orchiectomy) may be
and more inclusive and can help fully address the needs of individuals of
considered in select patients (See Principles of Surgery TEST-H 1 of 2 in
all sexual orientations and gender identities. NCCN Guidelines will
the algorithm). Unique clinical settings that warrant consideration for testis-
continue to use the terms men, women, female, and male when citing
sparing surgery include synchronous bilateral tumors, a solitary testicle
statistics, recommendations, or data from organizations or sources that do
with a mass suspicious for GCT, or a functionally solitary testicle with
not use inclusive terms. Most studies do not report how sex and gender
adequate gonadal function with respect to androgen production or sperm
data are collected and use these terms interchangeably or inconsistently.
production (eg, history of contralateral testicular atrophy).31-33 Transscrotal
If sources do not differentiate gender from sex assigned at birth or organs
biopsies of the testes should not be performed because violating the
present, the information is presumed to predominantly represent cisgender
scrotum increases the risk of local or atypical regional recurrence and can
individuals. NCCN encourages researchers to collect more specific data in
complicate management. In addition, a thorough history and physical
future studies and organizations to use more inclusive and accurate
examination should be performed. Serum tumor markers (LDH, AFP, and
language in their future analyses.
beta-hCG) also need to be assessed as they are used for prognosis and
staging.14 Marker levels should be assessed both before and after
Clinical Presentation, Workup, and Primary Treatment
orchiectomy. Elevated levels of beta-hCG, LDH, or AFP should be
Clinical Presentation followed up with repeated tests to allow for precise staging. Given the
Testicular cancer most often presents as a painless or painful testicular higher rates of hypogonadism in the testicular cancer population,
nodule, mass, enlargement, or induration (hardening). Often, patients will measuring baseline levels of gonadal function can also be considered.
present with testicular discomfort or swelling suggestive of epididymitis or
Primary Treatment
orchitis. A trial of antibiotics is never warranted in the treatment of a mass
suspicious for GCT, but can be considered in patients with pain without a Radical inguinal orchiectomy is the primary treatment for most patients
mass on further workup. Other patients may present with enlarged lymph who present with a testicular mass that is suspicious for malignancy on
nodes of the lower neck or upper chest (supraclavicular), a retroperitoneal ultrasound.34 A CT scan of the abdomen/pelvis with contrast or MRI with
mass, gynecomastia, venous thrombosis, or pulmonary embolism. and without contrast should be considered prior to orchiectomy if they can

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NCCN Guidelines Version 2.2024

Testicular Cancer

be done without delaying surgery as postoperative changes can 3) a clinical scenario where, due to the bulk, signs, or symptoms of
occasionally complicate the interpretation of scans completed after disease, the risk of delaying systemic therapy outweighs the benefit of a
orchiectomy. However, this is a minor concern and should not lead tissue diagnosis, chemotherapy may be initiated immediately without
clinicians to delay orchiectomy. Concurrent insertion of testicular waiting for a biopsy diagnosis or performing orchiectomy. Orchiectomy
prosthesis may be considered during radical inguinal orchiectomy if should be performed after completion of chemotherapy, oftentimes at the
desired by the patient.35-37 In cases where the ultrasound shows an time of RPLND or other adjunctive surgical procedures.
ambiguous abnormality that might be malignant, an open inguinal biopsy
(testis-sparing surgery or partial orchiectomy) with intraoperative frozen Staging
section analysis can be performed, but such cases are extremely rare.38
Staging of testicular GCTs is based on determination of the extent of
Reflex radical orchiectomy is recommended in most circumstances should
disease and assessment of post-orchiectomy levels of serum tumor
malignancy be detected. Similarly, an open inguinal biopsy of the
markers.14 The tumor (T), node (N), and metastasis (M) staging system
contralateral testis (inguinal exploration with exposure of testis, with direct
used by the AJCC is the internationally accepted standard for cancer
observation and partial orchiectomy) can be considered if an ambiguous
staging and is a major factor influencing prognosis and treatment
suspicious mass is identified on ultrasound or if the testis is cryptorchid or
decisions. The AJCC TNM staging system incorporates serum tumor
shows marked atrophy.39 However, biopsies are not recommended for
marker elevation as a distinct category (S), which is unique to this organ
testicular microcalcifications alone.
site. The extent of the primary tumor is classified after orchiectomy;
Sperm banking should be discussed with patients of reproductive age, if therefore, pathologic (p) staging is assigned to the primary tumor (T).
clinically indicated, before undergoing any therapeutic intervention that
The 8th edition of the AJCC Cancer Staging Manual introduced invasion of
may compromise fertility, including surgery, radiation therapy (RT),
the epididymis and hilar soft tissue as new pathologic criteria used for T
chemotherapy, or retroperitoneal lymph node dissection (RPLND).40-43 If
classification of stage I testicular GCTs.14,44 Due to the excellent clinical
sperm banking is desired, it should be performed before orchiectomy in
outcomes seen in testicular cancer, large-scale follow-up studies have
patients with a single testicle, those undergoing bilateral orchiectomy, and historically used tumor relapse rather than tumor-specific survival to
those with risk factors for infertility (atrophic contralateral testicle, history of
validate the relevance of pathologic parameters used for staging.14
infertility).
However, the association of hilar soft tissue and epididymal invasion with
Further management is dictated by histology, stage, and whether the relapse of stage I disease has not been validated. Current data only
cancer is a pure seminoma or a nonseminoma (nonseminomas include support their association with having advanced-stage disease at the time
mixed GCTs that are partially comprised of seminoma and tumors that are of diagnosis.45,46 Therefore, it is the opinion of the Panel that these factors
histopathologically described as pure seminomas in patients with elevated should not be used for clinical decision-making in the treatment of these
serum AFP). Although rare, when a patient presents with: 1) markedly patients. Instead, the NCCN Guidelines® for Testicular Cancer
elevated beta-hCG or AFP levels; 2) a testicular mass and/or disease recommend treating patients with stage I nonseminoma based on the
distribution typical for a testicular, retroperitoneal, or mediastinal GCT; and presence or absence of lymphovascular invasion (LVI), invasion of the

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NCCN Guidelines Version 2.2024

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spermatic cord, or invasion of the scrotum, which are risk factors known to based on the type of spermatic cord involvement (continuous vs.
be associated with an increased risk of relapse.47-56 Predominance of discontinuous).65 Therefore, for management decisions, the Panel
embryonal carcinoma has also been proposed as a prognostic indicator of recommends staging GCTs with discontinuous invasion of the spermatic
relapse in stage I nonseminoma, with several studies showing that a high cord as pT3 (high-risk stage I) and not as pM1 (stage III) as is
proportion of embryonal carcinoma in the primary tumor (>50%) is recommended by the AJCC. If surveillance is elected as primary
associated with an increased risk of relapse.49,57-64 However, very few treatment, the pelvis should be included in the imaging due to a higher risk
patients have a high volume of embryonal carcinoma without also having of pelvis relapses in these patients.
LVI, and the value of embryonal carcinoma predominance in predicting
To assess for metastatic disease, imaging studies of the chest, abdomen,
relapse in the absence of LVI is unclear.49,57,60,64 Therefore, predominance
and pelvis should be performed. Such studies typically include CT scans
of embryonal carcinoma is not used by the NCCN Guidelines for Testicular
of the abdomen and pelvis and CT scan or x-ray of the chest.
Cancer to risk stratify patients with stage I nonseminoma. Patients with
Fluorodeoxyglucose (FDG)-PET scans should not be used to stage
stage I nonseminoma with a high volume of embryonal carcinoma and no
testicular GCTs. In select patients, brain MRI should also be performed;
evidence of LVI are neither high risk nor low risk and could be considered
these patients include those with neurologic symptoms, post-orchiectomy
for adjuvant therapy. The NCCN Guidelines do not recommend risk-
serum beta-hCG >5000 IU/L, non-pulmonary visceral metastases, or
adapted treatment for stage I pure seminoma.
extensive lung metastases. In patients who had elevated serum tumor
The 8th edition of the AJCC Cancer Staging Manual also introduced markers prior to orchiectomy, it is important to obtain the half-life kinetics
changes to pathologic staging based on the type of spermatic cord of the tumor markers after orchiectomy if the markers are declining
involvement. Currently, continuous involvement of the spermatic cord soft because a slower-than-expected decline often indicates the presence of
tissue by the primary tumor is staged as pT3, whereas discontinuous metastatic disease.
spermatic cord involvement by invasion of lymphovascular spaces is now
In 2016, the World Health Organization (WHO) tumor classification
considered as a metastatic deposit (pM1).14 This significant change results
scheme was significantly modified to contain new entities for GCTs.66
in patients with discontinuous spermatic cord involvement being upstaged
Major changes include a pathogenetically derived classification using
from high risk stage I to stage III disease independent of radiologic or
germ cell neoplasia in situ (GCNIS) of the testis as the new WHO-
serologic assessment, which the Panel is concerned may lead to
recommended term for precursor lesions of invasive GCTs, and the
overtreatment. The evidence used to support this change is unclear;
distinction between testicular GCTs derived from GCNIS (postpubertal)
presently, there are no persuasive data showing differences in clinical
and those unrelated to GCNIS (prepubertal).66,67 Additionally,
outcomes between patients with discontinuous spermatic cord involvment
spermatocytic seminoma has been renamed as spermatocytic tumor, to
compared to patients with continuous involvement. A recent retrospective
avoid potential confusion with the unrelated usual seminoma. Presently,
analysis assessing the impact of different patterns of spermatic cord
reporting of anaplasia (seminoma or spermatocytic tumor) or
involvement on clinical stage and patient outcomes found no significant
distinguishing mature from immature teratoma is not required, since these
differences in either clinical stage at presentation or risk of recurrence
do not have demonstrable prognostic importance. Conversely, the

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Testicular Cancer

presence of somatic-type malignancy arising in teratomas indicates more ULN have a worse prognosis than other patients with good risk. However,
aggressive behavior, and should therefore be reported. currently there are insufficient data to recommend treating these patients
differently based on LDH level (see discussion below).
Risk Classification for Advanced Disease
In 1997, the International Germ Cell Cancer Consensus Group (IGCCCG) Pure Seminoma
defined a classification system based on identification of clinically If a pure seminoma is detected, an abdomen/pelvis CT scan with contrast
independent prognostic features such as extent of disease and post- or MRI with and without contrast should be performed unless previously
orchiectomy levels of serum tumor markers. This classification system performed prior to orchiectomy to assess the retroperitoneal lymph nodes.
categorizes patients with testicular GCTs into good-, intermediate-, or A chest x-ray is also recommended. A chest CT is indicated if the
poor-risk groups.68 When determining a patient’s risk classification, the abdomen/pelvis CT or the chest x-ray shows evidence of metastatic
relevant serum tumor marker value is the value on day 1 of cycle one of disease. Measurement of beta-hCG, LDH, and AFP levels should be
first-line chemotherapy. Definitions of stage and risk classification in these repeated since TNM staging is based on post-orchiectomy levels. For
guidelines are done according to the IGCCCG classifications. patients with elevated pre-orchiectomy beta-hCG levels, beta-hCG levels
The IGCCCG classification system plays a pivotal role in the management should be followed with repeated determinations after orchiectomy to
of metastatic GCTs, but relies on old data of patients treated between determine their trajectory and, if declining, their nadir. The expected half-
1975 and 1990. The IGCCCG Update Model, published in 2021, included life for beta-hCG is ≤3 days. Beta-hCG and LDH may be elevated in
data from 9728 males with metastatic nonseminomatous GCTs treated patients with seminoma. Mild to moderate elevations of beta-hCG (S1) are
with EP-based first-line chemotherapy between 1990 and 2013 at not used to risk stratify pure seminomas, but a level of 5000 IU/L, which is
institutions in Europe, North America, and Australia.69 Compared with the the cutoff for S2, is not generally thought to be compatible with a pure
original IGCCCG publication, 5-year progression-free survival (PFS) seminoma. Therefore, patients with a histopathological diagnosis of pure
remained similar in patients with good or intermediate risk (89% vs. 90% seminoma and a beta-hCG of ≥5000 would be treated as an intermediate
and 75% vs. 78%, respectively), but the 5-year overall survival (OS) or poor-risk nonseminoma, depending on the extent of beta-hCG levels.
increased from 92% to 96% in good-risk and from 80% to 89% in Whether an elevated LDH should be used to stage or risk stratify patients
intermediate-risk patients. In poor risk patients, the 5-year PFS increased with pure seminoma is controversial and practice patterns vary. For
from 41% to 54% and the OS from 48% to 67%. Furthermore, a novel patients with otherwise good-risk disseminated seminoma (stage II–III), an
prognostic model for PFS was developed in 3543 patients and validated in LDH >2.5 × ULN is associated with a worse prognosis, but there is no
an independent dataset. This more granular prognostic model identified a consensus as to whether treatment for such patients should therefore be
new cutoff of LDH at 2.5 × ULN, increasing age, and presence of lung intensified.37 Some Panel members advocate treating them as other
metastases as additional adverse prognostic factors. An online calculator patients with good risk while others advocate a more aggressive approach
is provided (https://www.eortc.org/IGCCCG-Update). It should be noted (such as three cycles of bleomycin, etoposide, and cisplatin (BEP) plus a
that patients with good risk disseminated seminoma with an LDH >2.5 × fourth cycle using etoposide and cisplatin (EP).

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NCCN Guidelines Version 2.2024

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For patients with normal imaging (ie, stage I), rising or persistently Surveillance
elevated beta-hCG levels generally indicate the presence of metastatic
Several studies evaluating surveillance for the management of stage I
disease (stage IS). Beta-hCG levels >1000 IU/L post-orchiectomy may
seminoma have been conducted.71-76 The relapse rates seen in these
indicate the presence of nonseminomatous tumor elements. An elevated
studies have ranged from 15% to 20%, with most disease relapse
AFP pre- or post-orchiectomy indicates the presence of nonseminomatous
detected in the infradiaphragmatic lymph nodes. The best established risk
elements unless another cause of the elevated AFP (such as liver
factor for relapse of pure seminoma is larger size of the primary tumor.77
disease) is identified. Patients with seminoma arising from an
As the tumor size increases, the risk of relapse also increases, but any
extragonadal site, like the mediastinum, are usually diagnosed via biopsy
cutoff point is arbitrary.71,73,78,79-81 Although the 8th edition of the AJCC
and treated with standard chemotherapy regimens according to risk
Cancer Staging Manual uses a cutoff point of 3 cm to subclassify stage IA
classification. Brain MRI is recommended if beta-hCG levels exceed 5000
pure seminoma into pT1a and pT1b, this small cutoff size was chosen in
IU/L (as noted above, a beta-hCG >1000 IU/L is rare in seminoma and a
an effort to be conservative due to the large variability in size cutoffs
value >5000 IU/L is generally indicative of a nonseminomatous GCT), if
reported in the literature.14 Additionally, some studies have reported that
there is extensive metastatic disease in the lungs, or if non-pulmonary
rete testis invasion is an independent risk factor for relapse in stage I pure
visceral metastases or neurologic symptoms are present. Sperm banking
seminoma while others have reported that it is not.71,73,77-79,82 A systematic
should be recommended, if clinically indicated, to patients who will be
review also determined that rete testis invasion is significantly associated
undergoing chemotherapy, RT, or RPLND if they wish to preserve fertility.
with risk of relapse in patients with stage I seminoma treated with
surveillance.82 In contrast, another systematic review found rete testis
Pure Seminoma Stages IA and IB
invasion to be significantly associated with relapse in only 4 of the 13
Primary Treatment for Pure Seminoma Stages IA and IB studies analyzed.77 Due to these concerns, the NCCN Panel discourages
Since most patients with stage I pure seminoma are cured by orchiectomy risk-adapted management in stage I pure seminoma and instead strongly
alone, the NCCN Panel strongly prefers surveillance for pT1–pT3 tumors recommends surveillance for all patients who are able to adhere to the
as the standard post-orchiectomy treatment option for these patients. surveillance schedule. If surveillance is not applicable, alternative options
However, since 15% to 20% of patients on surveillance will experience are either adjuvant chemotherapy with single-agent carboplatin or
relapse, the Panel recommends chemotherapy with one or two cycles of adjuvant RT as described below. Each approach has distinct advantages
single-agent carboplatin (with imaging recommended within 4 weeks prior and disadvantages that should be discussed with patients and their
to initiation, even if scans have been performed previously), or RT (20 Gy families to select the best individual treatment plan.
or 25.5 Gy) as alternative options to decrease the risk of relapse in certain
patients. Disease-specific survival for stage I disease approaches 100% Adjuvant Chemotherapy
irrespective of the management strategy used.70 Oliver et al reported the initial results of a trial that randomized 1477
patients with stage I seminoma to receive either RT (n = 885) or one cycle
of intravenous carboplatin (n = 560) at the dose area under the curve

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NCCN Guidelines Version 2.2024

Testicular Cancer

(AUC) x 7 (ie, based on the formula 7 x [glomerular filtration rate (GFR, Use of two cycles of adjuvant carboplatin in this setting has also been
mL/min) + 25 mg]).83 At a follow-up of 3 years, the relapse-free survival studied. The Spanish Germ Cell Cancer Cooperative Group reported that
rates for both groups were similar (95.9% for the RT group and 94.8% for among 412 males treated with two cycles of adjuvant carboplatin for high-
the carboplatin group), which established the noninferiority of carboplatin risk stage I seminoma, the 10-year relapse-free survival rate was 97% and
compared to RT.83 The mature results of this trial confirmed the 10-year OS was 100%.89-91 The efficacy of two cycles of adjuvant
noninferiority of single-dose carboplatin versus RT in terms of relapse-free carboplatin was confirmed in a study by the Hellenic Cooperative
survival.84 In an intent-to-treat analysis, the relapse-free survival rates at 5 Oncology Group, which reported a 5-year relapse-free survival rate of
years were 96% in the RT arm and 94.7% in the carboplatin arm (hazard 96.8% among 138 patients with stage I seminoma treated with this
ratio [HR], 1.25; P = .37). One seminoma-related death occurred after RT regimen.92 A recent prospective study reported the treatment outcomes of
and none occurred after carboplatin. Additionally, patients given 725 patients with stage I seminoma treated with surveillance, one cycle of
carboplatin were less lethargic and less likely to take time off from work carboplatin, or two cycles of carboplatin.93 Although disease-specific
than patients receiving RT. Therefore, the authors concluded that a single survival was 100% for all three strategies, crude relapse rates were
dose of carboplatin is less toxic and as effective in preventing disease significantly higher with the one-cycle regimen (5%) compared to the two-
relapse as adjuvant RT in males with stage I pure seminoma after cycle regimen (1.5%) after a median follow-up of 30 months. The crude
orchiectomy.84 However, it should be noted that there are limited long-term relapse rate for surveillance was 8.2%. Furthermore, one cycle of
follow-up data regarding the toxicity and efficacy of carboplatin.71,85 A carboplatin demonstrated low efficacy to control large tumors. In the
recent non-randomized population-based study of 897 patients with stage absence of randomized data comparing one versus two doses of
I seminoma suggested that patients with tumor size >4 cm, rete testis carboplatin, as well as the lack of long-term data, the Panel does not
invasion, or both derive a smaller reduction in relapse rate with one cycle recommend one dose over the other. Regardless of the regimen used,
of carboplatin than previously reported.71,73,85 After a median follow-up of imaging is recommended within 4 weeks prior to the initiation of
5.6 years, the relapse rate in patients with one or both risk factors was chemotherapy to confirm staging, even if scans were previously
15.5% for patients treated with surveillance versus 9.3% for patients who performed.
received one cycle of carboplatin.71 An absolute reduction in the risk of
relapse by only 6.2% may not be sufficient to justify the use of single-cycle Adjuvant Radiation Therapy
adjuvant carboplatin.85 Platinum-based chemotherapy has been Numerous studies have found an increased risk for late toxicities,
associated with cardiac toxicity and an increased risk for secondary including development of secondary malignancies, in patients with
cancers.86-88 However, whether such long-term risks ensue from single- seminoma treated with RT; however, many of these patients were treated
agent carboplatin as dosed for seminoma remains unknown. Therefore, at a time when treatment fields were larger and radiation doses were
more data are needed to assess the value of one cycle of carboplatin in higher than those currently used.94,95 One population-based study reported
treating patients with stage I seminoma. that RT for stage I seminoma was associated with an 80% increase in the
risk of death from secondary cancers.96 Another study found that
moderate-dose infradiaphragmatic RT for stage I seminoma was

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associated with an increased risk for secondary cancers in organs within Follow-up for Pure Seminoma Stages IA and IB After Primary Treatment
the radiation field.97 A recent multicenter cohort study reached similar Although no single follow-up plan is applicable to all patients, the NCCN
conclusions, reporting that the risk of developing an infradiaphragmatic Panel has provided guidance for the follow-up of patients with testicular
solid malignant neoplasm increased by 8% per Gy of radiation dose GCTs for the first 5 years after the completion of therapy. These
administered (95% CI, 6%–9%; P < .001).88 Additionally, one study recommendations may be individualized and extended beyond 5 years at
reported that RT might increase the risk of a subsequent cardiac event,86 the discretion of the physician. Follow-up strategies for patients with stage
but other analyses have not confirmed this risk.96 I seminoma vary according to the treatment modality received by the
Nodal mapping studies suggest that treatment fields should target the patient (surveillance vs. adjuvant treatment). An analysis of >5000 patients
retroperitoneal lymph nodes but not necessarily the ipsilateral renal hilar with stage I seminoma from various trials reported that the 5-year relapse
nodes. 98,99
Special circumstances, such as ipsilateral pelvis surgery, may rate was higher with surveillance (18.6%) compared to RT (4.8% with
alter the lymphatic drainage of the testis. Therefore, irradiation of the extended-field RT and 3.6% with para-aortic RT) or chemotherapy (6.1%
ipsilateral iliac and inguinal lymph nodes has been advocated in such with one cycle of carboplatin and 2.3% with two cycles of carboplatin).103
patients.98,100,101 It should be noted that patients treated with para-aortic An analysis of data from the Danish Testicular Cancer database reached
RT have a slightly higher rate of pelvis relapse compared with those similar conclusions, reporting that the 10-year cumulative incidence of
treated with “dog-leg’’ RT. 101-104
Prophylaxis to the mediastinum is not disease recurrence was 32% for patients with high-risk (tumor size ≥6 cm)
provided, because relapse rarely occurs at this site and mediastinal stage I seminoma given surveillance versus 2.8% for those given adjuvant
radiotherapy introduces additional toxicities and late effects. RT.107 An analysis of data from the National Cancer Database examined
the survival outcomes of 33,094 patients with stage I seminoma who
The NCCN Panel prefers surveillance to the routine use of adjuvant
received surveillance, chemotherapy, or RT as primary treatment after
therapy for patients with stage I seminoma because the risk of relapse is
orchiectomy.108 Although OS was high for all strategies, results showed a
low when considered in relation to the potential harms of adjuvant therapy.
small absolute survival advantage for adjuvant therapy (RT or
However, if adjuvant chemotherapy is given, the NCCN Panel
chemotherapy) over surveillance at 10 years (95% vs. 93.4%; HR, 0.58; P
recommends carboplatin (AUC x 7) for either one or two cycles for
< .0005). However, in this study, surveillance was defined as not having
patients with stage IA or IB pure seminoma. If RT is delivered, the Panel
undergone radiation or chemotherapy, meaning that no distinction was
recommends a total dose of 20 Gy be administered in 10 fractions of 2.0
made between patients who underwent surveillance and patients who
Gy each.105 Alternatively, a total dose of 25.5 Gy can be given in 17
never followed up. Thus, patients for whom active treatment was
fractions of 1.5 Gy each.106 Other RT dose schedules are listed in the
recommended but who never came in for treatment would have been
Principles of Radiotherapy for Pure Testicular Seminoma in the algorithm
considered to have undergone surveillance even if they never had any
(see Table 1 on TEST-C 2 of 5). Patients at higher risk for morbidity from
surveillance visits or tests. Independent of the treatment modality received
RT, such as those with a history of inflammatory bowel disease or prior
by the patient, the risk of relapse is highest in the first 2 years following
RT, are generally not given primary RT.
treatment.103 In the event of relapse, clinicians should keep in mind the
potential for development of a second primary tumor in the contralateral
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NCCN Guidelines Version 2.2024

Testicular Cancer

testis. Reassessment of disease activity should be performed in patients occurring beyond 3 years. Relapse treatment outcomes were good, with
with new or worsening signs or symptoms of disease, and patients 81% of patients experiencing a complete response with no tumor-related
experiencing relapse should be treated according to the extent of the deaths. Five-year disease-free survival (DFS) and OS were also similar
disease with those previously on surveillance being treated with RT or across groups, suggesting non-inferiority of MRI or reduced CT schedule
chemotherapy and those who received carboplatin or RT being treated to standard CT schedule for surveillance of patients with stage I
with first-line cisplatin based chemotherapy (see First-Line Chemotherapy seminoma. Thus, MRI is an appropriate option that can be considered to
Regimens for Germ Cell Tumors [TEST-E]). replace abdomen/pelvis CT. The MRI protocol should include visualization
of all the nodes that need to be assessed, including retroperitoneal and
Follow-up During Surveillance pelvis nodes.
Follow-up for patients with stage I seminoma treated with surveillance Several studies have suggested that relapses in the lung are rarely
after orchiectomy is outlined in Table 1 on TEST-A 1 of 3 in the algorithm detected by chest x-ray alone in patients with stage I seminoma treated
and includes a history and physical examination with optional with surveillance.111-113 In a recent retrospective analysis of 886 patients
measurement of serum tumor markers. The measurement of serum tumor with stage I seminoma, 83 patients experienced relapse.112 All relapses
markers is optional due to the rarity of marker-only relapse, since most were detected by either rising tumor markers and/or follow-up CT scan;
patients with elevated markers will also have evidence of relapse on not a single relapse was detected by routine chest x-ray alone. Other
imaging. Additionally, in one of the largest prospectively maintained studies have reported similar results, calling into question the value of
databases of patients with stage I seminoma treated with surveillance, it chest x-rays in surveillance settings for stage I seminomatous GCTs.111,113
was reported that routine measurement of serum tumor markers did not Therefore, routine chest imaging, including chest x-ray and chest CT with
aid in the early diagnosis of relapse.109 Therefore, routine measurement of contrast, should be reserved for patients with thoracic symptoms.
serum tumor markers can be safely omitted from stage I seminoma
surveillance schedules. Follow-up After Adjuvant Treatment
There is controversy regarding how many imaging studies should be Follow-up of patients treated with adjuvant therapy (chemotherapy or RT)
performed in patients on surveillance. A phase III clinical trial in the United is outlined in Table 2 on TEST-A 1 of 3 in the algorithm and includes a
Kingdom entitled TRISST (MRC TE24/Trial of Imaging and Schedule in history and physical examination (testicular ultrasound for any equivocal
Seminoma Testis) investigated whether MRI or a reduced CT schedule exam), with optional measurement of post-orchiectomy serum tumor
could be used as a safe and effective alternative to standard CT-based markers. A meta-analysis of 2466 patients reported that relapse rarely
surveillance in the management of stage I seminoma.110 The trial occurred >3 years after treatment with RT or carboplatin (0.2% of
randomized 669 patients with stage I seminoma post-orchiectomy to patients).70 Since the rate of relapse beyond 3 years is very low for
receive 7 CTs, 7 MRIs, 3 CTs, or 3 MRIs at selected intervals. After a patients treated with chemotherapy or RT, the NCCN Panel recommends
median follow-up of 72 months, 12% of patients had relapsed. In all performing an abdomen/pelvis CT scan or MRI with or without contrast
groups, most relapses were detected at scheduled imaging with very few annually for the first 3 years only. The MRI protocol should include

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Testicular Cancer

visualization of the retroperitoneal and pelvis nodes. Chest x-rays should rates and potential for dual therapy with each treatment option. Moreover,
be obtained only when clinically indicated, and chest CT scans with to confirm staging before initiating treatment in select cases of stage IIA
contrast should be considered for patients who are symptomatic. CT is not disease with borderline retroperitoneal lymph nodes, waiting 4 weeks after
recommended beyond 5 years, unless clinically indicated. Relapses are initial imaging assessment and repeating imaging (CT or MRI) may be
treated according to the stage at relapse.70 However, patients should not considered.
be treated based on an elevated LDH level alone.
Options for the primary treatment of stage IIA and IIB seminomas include
RT or first-line chemotherapy with three cycles of BEP or four cycles of
Pure Seminoma Stage IS
EP.114-116 Nerve-sparing RPLND is also an option for stage IIA disease. If
Primary Treatment for Pure Seminoma Stage IS chemotherapy is given, both EP and BEP are preferred regimens in this
Stage IS pure seminoma is very uncommon and requires persistent setting. However, a bleomycin-free regimen should be considered in
elevation of serum tumor markers following orchiectomy. Elevated tumor patients at risk for bleomycin-related toxicity, such as those with reduced
markers increase the risk of disease outside the retroperitoneum; GFR or older age. The presence of chronic obstructive pulmonary disease
therefore, systemic therapy should be encouraged. However, physicians (COPD) or other lung disease resulting in reduced pulmonary function are
are cautioned against treating a patient based on mildly elevated LDH or also risk factors for bleomycin-related toxicity. Different studies have
beta-hCG alone, as other causes may be responsible for elevation of reported different outcomes with regard to whether chemotherapy or RT is
these markers. Persistent elevation of serum markers is usually evidence more effective in this setting. Two studies used data from the National
of metastatic disease, which will show up radiographically if doubt exists in Cancer Database to assess survival outcomes according to treatment
the diagnosis. strategy in patients with stage IIA/B seminoma. A retrospective study by
Glaser et al compared RT with multi-agent chemotherapy in 1772 patients
Follow-up for Pure Seminoma Stage IS with stage IIA–C seminoma treated with orchiectomy.117 After a median
The NCCN Panel recommends repeating measurements of serum tumor follow-up of 65 months, 5-year OS was significantly higher with RT
markers and performing imaging studies (chest/abdomen/pelvis CT with compared to chemotherapy in patients with stage IIA seminoma (99% vs.
contrast) to scan for evaluable disease. 93%; HR, 0.28; 95% CI, 0.09–0.86; P = .027). However, no significant
difference in 5-year OS was seen in patients with stage IIB seminoma
Pure Seminoma Stages IIA and IIB treated with post-orchiectomy RT or chemotherapy (95.2% vs. 92.4%). A
Primary Treatment for Pure Seminoma Stages IIA and IIB similar study by Paly et al evaluated data from the same database during
the same time period and reached similar conclusions. This retrospective,
Stage IIA pure seminoma is defined as metastatic disease to lymph non-randomized study evaluated 1885 patients with stage IIA/B seminoma
nodes, with a lymph node mass measuring ≤2 cm in greatest diameter.14 A selected to receive either first-line chemotherapy or RT following
lymph node mass measuring 2 to 5 cm in greatest diameter is classified as orchiectomy.118 Receipt of chemotherapy was associated with decreased
stage IIB disease.14 Providers should engage in shared decision-making 5-year OS in patients with stage IIA seminoma (HR, 13.33; P < .01), but
for stage IIA seminoma that includes informing patients of the recurrence

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NCCN Guidelines Version 2.2024

Testicular Cancer

not in patients with stage IIB seminoma (HR, 1.39; P = .45). These studies arrangement, see Principles of Radiotherapy for Pure Testicular
were not randomized trials and treatment decisions were based on the Seminoma in the algorithm.
treating physician’s clinical judgment, which presumably was influenced by
the specific characteristics of each patient. Therefore, it is possible that Although primary treatment with RT or first-line chemotherapy results in
patients with more extensive disease were selected for chemotherapy. favorable survival outcomes, they bear the risks of acute and late toxic
Nevertheless, these studies provide some support for the use of RT over effects. Therefore, evaluation and development of alternative strategies is
chemotherapy to treat stage IIA seminoma. In contrast, a study by of interest in order to mitigate toxicity while maintaining efficacy.
Mortensen et al evaluating 363 patients with stage II–III seminoma Prospective and retrospective studies have reported the use of primary
reported that the relapse rate was 6% among patients treated with RPLND in clinical stage II seminoma with curative intent and
chemotherapy compared to 12.6% among those treated with RT. It should demonstrated that RPLND can cure many clinical stage II seminomas with
be noted that chemotherapy was used for more advanced stage disease a 2-year recurrence free survival of 72% to 90%, allowing patients to avoid
than RT in this study.81 This has led some physicians to prefer chemotherapy and radiotherapy.120-123 Due to these results, the Panel
chemotherapy for patients with stage II seminoma; however, these results included RPLND as an option for stage IIA disease within 4 weeks of CT
must be interpreted with caution since this study was not a randomized scan and within 7 to 10 days of confirmation of normal tumor markers.
trial and did not specifically compare the two treatment modalities for Referral to a high volume center with experience in performance of this
stage IIA disease. Therefore, the Panel recommends either RT or first-line procedure is also recommended. Additionally, the recent single-arm phase
chemotherapy as primary treatment for both stage IIA and IIB seminoma. II SAKK (01/10) trial investigated whether one cycle of single-agent
However, for patients with stage IIB seminoma, RT should be reserved for carboplatin followed by involved-node RT was effective in treating patients
select patients with non-bulky (≤3 cm in transaxial long axis) disease.114 with stage IIA or IIB seminoma (N = 116) with minimal toxicity.124 After a
median follow-up of 4.5 years, the 3-year PFS was 93.7%, which was
The target fields for RT for stage IIA/B disease should include the para-
short of the target 3-year PFS of 95%. Although the study failed to meet its
aortic and proximal ipsilateral iliac lymph nodes. Treatment is delivered in
primary endpoint, survival was favorable and toxic effects were minimal
two consecutive anteroposterior-posteroanterior (AP/PA) phases with no
with this treatment strategy. Grade 3–4 treatment-related adverse events
break in between. The initial phase consists of treatment of modified dog-
included neutropenia, thrombocytopenia, and vomiting, which occurred in
leg fields at a dose of 20 Gy delivered in 10 fractions of 2.0 Gy each or
4%, 3%, and 1% of patients, respectively. No treatment-related deaths
25.5 Gy delivered in 17 fractions of 1.5 Gy each. The Panel prefers
and no late toxic effects were reported. Serious adverse events were
modified dog-leg fields as described by Classen et al.114 The second
reported in only 4% of patients. However, more data is needed before
phase (cone down) consists of daily 1.8- to 2-Gy fractions to a cumulative
recommending this treatment strategy as an alternative to traditional RT or
total dose of 30 Gy for patients with stage IIA seminoma and 36 Gy for
cisplatin-based chemotherapy in patients with stage II seminoma.
patients with stage IIB seminoma.114 Prophylactic mediastinal RT is not
indicated for the management of stage II disease.119 For details on field

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NCCN Guidelines Version 2.2024

Testicular Cancer

Follow-up for Pure Seminoma Stages IIA and Non-bulky IIB After Pure Seminoma Stages IIC and III
Radiotherapy or Postchemotherapy
Primary Treatment for Pure Seminoma Stages IIC and III
The recommended follow-up schedule for patients with stage IIA and non-
Patients with stage IIC or stage III seminomas are classified as either
bulky stage IIB seminoma after RT or chemotherapy, assuming no
good or intermediate risk. All stage IIC and stage III seminomas are
residual mass or residual mass <3 cm and normal tumor markers, is
considered good risk except for stage IIIC disease, which involves non-
outlined in Table 3 on TEST-A 2 of 3 in the algorithm and includes a
pulmonary visceral metastases (eg, bone, liver, brain) and is considered
history and physical examination with optional measurement of post-
intermediate risk. Standard first-line chemotherapy is used for both groups
orchiectomy serum tumor markers and imaging (abdomen/pelvis CT scan
of patients.
with contrast or MRI with and without contrast). The MRI protocol should
include visualization of the retroperitoneal and pelvic nodes as well as all For patients with good risk patients, three cycles of BEP or four cycles of
other nodes that need to be assessed. CT is not recommended beyond 5 EP are recommended (both preferred).125-127 The two regimens have not
years, unless clinically indicated. Chest x-ray is recommended and may be been compared head-to-head in patients with seminoma, so the Panel
used for routine follow-up, but chest CT with contrast is preferred in the recommends that a number of factors be considered in choosing between
presence of thoracic symptoms. the two. The specific schedule of the two regimens is different (9 weeks for
three cycles of BEP compared to 12 weeks for four cycles of EP), which
Follow-up for Pure Seminoma Stage IIA Post-primary RPLND and NOT
Treated with Adjuvant Chemotherapy
may make one more convenient for certain patients. While etoposide and
cisplatin are associated with a dose-dependent increased risk of
The recommended follow-up schedule for patients with stage IIA secondary cancers, there are no data addressing whether the risk is
seminoma after RPLND not treated with adjuvant chemotherapy is significantly higher with four cycles than with three. Bleomycin, which is
outlined in Table 4 on TEST-A 2 of 3 in the algorithm and includes a cleared by the kidneys, is associated with a risk of pneumonitis and
history and physical examination with optional measurement of serum diminished pulmonary function. Therefore, four cycles of EP are generally
tumor markers as well as imaging with abdomen/pelvis CT scan with preferable in patients with a reduced GFR (who would be expected to
contrast or MRI with and without contrast The MRI protocol should include clear bleomycin more slowly), in patients >50 years of age and over (since
visualization of the retroperitoneal and pelvis nodes as well as all other renal function decreases with age), and in patients with COPD or other
nodes that need to be assessed. The same imaging schedule is also lung disease resulting in significantly diminished pulmonary function.
recommended for chest x-ray and may be used for routine follow-up, but a Some oncologists prefer four cycles of EP for heavy smokers regardless
chest CT with contrast is preferred in the presence of thoracic symptoms. of lung function. The different risks associated with each regimen may
lead individual patients to prefer one regimen over the other. The
physician and patient should make a shared decision informed by patient
clinical characteristics and preferences.

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NCCN Guidelines Version 2.2024

Testicular Cancer

For patients with intermediate-risk disease, more intensive chemotherapy uptake of FDG on PET scans, often resulting in unclear images of
with four cycles of BEP (preferred) or four cycles of etoposide, mesna, testicular lesions.139 Additionally, the abdomen and retroperitoneal space
ifosfamide, and cisplatin (VIP) is recommended.128-133 VIP should be are sites of non-specific FDG uptake, which can lead to false-positive
reserved for patients with a contraindication to bleomycin (ie, a reduced or results.139 Possible sources of false-negative results include small
borderline GFR, aged >50 years, COPD, or other lung disease), but it malignant lesions (<3 cm) and lesions with low proliferative indices.138
should be kept in mind that this regimen is high risk for febrile neutropenia Therefore, accurate interpretation of FDG-PET scans is paramount and
and granulocyte colony-stimulating factors (G-CSFs) should be used (See possible positive findings should be corroborated with the corresponding
the NCCN Guidelines for Hematopoietic Growth Factors). All of these CT results. FDG-PET/CT is not indicated for residual masses ≤3 cm due
chemotherapy options are category 1 recommendations except for VIP, to its low diagnostic accuracy in small tumors.138 To reduce the incidence
which is a category 2A recommendation. of false-positive results due to inflammation, the FDG-PET/CT scan should
be performed at least 6 weeks after the completion of the last cycle of
Management of Pure Seminoma Stages IIA, IIB, IIC, and III After chemotherapy in patients with a residual mass >3 cm and normal serum
Chemotherapy
tumor marker levels.138,140 A negative FDG-PET/CT following
After primary treatment with first-line chemotherapy, patients with stage chemotherapy is very reassuring. If the FDG-PET/CT is negative,
IIA, IIB, IIC, or III seminoma should be evaluated by CT scan with contrast surveillance is recommended as described in the below section on Follow-
or MRI with and without contrast of the chest, abdomen, and pelvis as well up for Pure Seminoma Bulky Stage II and Stage III After Chemotherapy. If
as measurement of serum tumor markers. Patients with normal serum results are indeterminate, the FDG-PET/CT or CT scan should be
AFP and beta-hCG levels and either no residual mass or a residual mass repeated in 6 to 8 weeks. If the FDG-PET/CT is positive, resection or
≤3 cm should undergo surveillance as described in Table 3 on TEST-A 2 interventional radiology (IR)-guided biopsy of the residual mass should be
of 3 in the algorithm and discussed in the section above on Follow-up for considered. An alternative strategy is to repeat FDG-PET/CT scan in 8 to
Pure Seminoma Stages IIA and Non-bulky IIB After Radiotherapy or 12 weeks to assess for changes. If the mass is persistently FDG-avid on
Postchemotherapy. PET/CT, then resection or biopsy is recommended. If PET/CT is still
indeterminate, CT scan or biopsy are recommended.
Surveillance is also recommended for patients with a residual mass >3 cm
and normal serum AFP and beta-hCG levels. A FDG- PET/CT scan from If the residual disease is completely resected and histopathology shows
skull base to mid-thigh can be considered to better delineate the presence viable seminoma, two cycles of adjuvant chemotherapy can be considered
of viable residual tumor since CT alone cannot discriminate between with the following regimens: EP, TIP (paclitaxel, ifosfamide, cisplatin),141
residual neoplastic lesions and necrotic or fibrotic tissue.134-138 FDG-PET VIP, or VeIP (vinblastine, mesna, ifosfamide, cisplatin).142,143 If the
can provide useful metabolic information on these lesions, which may aid resection is incomplete and the pathology shows viable seminoma, or if
in the early detection of recurrent disease in patients with normal CT there is progressive disease (growing mass or rising markers), a full
findings, since functional abnormalities usually precede morphologic course of second-line chemotherapy (four cycles of TIP or four cycles of
ones.138 However, testicular GCTs are typically slow-growing and have low VeIP; both preferred) is recommended.141-144 In rare cases,

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NCCN Guidelines Version 2.2024

Testicular Cancer

nonseminomatous elements may be identified in the biopsy specimen. If frequent imaging based on clinical judgment. A FDG-PET/CT scan of the
these elements are non-teratomatous, then management should proceed skull base to mid-thigh can be conducted if clinically indicated. Since
in the same fashion as for viable seminoma. Following adjuvant or viable tumor cells have been found in tumors >3 cm with a negative post-
second-line chemotherapy, patients should undergo follow-up as chemotherapy FDG-PET scan,145 the NCCN Panel recommends that
discussed in the upcoming sections. Patients should also adhere to this patients with a residual mass measuring >3 cm and negative FDG-PET
follow-up schedule if their biopsy results are negative for viable seminoma. results after chemotherapy should undergo an MRI with and without
contrast or abdomen/pelvis CT scan with contrast every 6 months for the
Follow-up for Pure Seminoma Stage IIA After Primary RPLND and Adjuvant first year and then annually for 5 years.
Chemotherapy
Nonseminoma
The recommended follow-up schedule for patients with stage IIA
seminoma after primary RPLND and adjuvant chemotherapy treatment is Nonseminomatous GCTs include nonseminoma tumors, mixed
outlined in Table 5 on TEST-A 3 of 3 in the algorithm and includes a seminoma/nonseminoma tumors, and seminoma tumors in patients with
history and physical examination and optional tumor marker assessment. elevated serum AFP levels. To assess for metastatic disease, CT scans
Abdomen/pelvis CT with contrast or MRI with and without contrast is with contrast or MRI with and without contrast of the chest, abdomen, and
recommended, and the MRI protocol should include all nodes that need to pelvis should be performed. Use of FDG-PET/CT scan is not clinically
be assessed. Chest x-ray is recommended, and while chest x-ray may be indicated for nonseminoma.146,147 In select patients, brain MRI should also
used for routine follow-up, a chest CT with contrast is preferred in patients be performed; these patients include those with neurologic symptoms,
demonstrating thoracic symptoms. post-orchiectomy serum beta-hCG >5000 IU/L or AFP >10,000 ng/mL,
predominance of choriocarcinoma, non-pulmonary visceral metastasis, or
Follow-up for Pure Seminoma Bulky Stage II and Stage III After extensive lung metastases. Elevated levels of serum beta-hCG, LDH, or
Chemotherapy
AFP should be followed up with repeated tests as TNM staging is based
The recommended follow-up schedule for patients with bulky clinical stage on post-orchiectomy values. In patients who had elevated serum tumor
IIB, IIC or stage III seminoma after treatment with chemotherapy is markers prior to orchiectomy, it is important to obtain the half-life kinetics
outlined in Table 6 on TEST-A 3 of 3 in the algorithm and includes more of the tumor markers after orchiectomy if the markers are declining,
frequent history and physical examination as well as optional because a slower-than-expected decline often indicates the presence of
measurement of serum tumor marker levels. Abdomen/pelvis CT scans metastatic disease. The NCCN Panel emphasizes that mildly elevated,
with contrast or MRI with and without contrast are recommended, and the non-rising AFP levels may not indicate the presence of a GCT. Therefore,
MRI protocol should include all nodes that need to be assessed. Chest x- decisions to treat should not be based on AFP levels <20 ng/mL. Similarly,
ray is recommended for routine follow-up; however, chest CT with contrast further workup should be considered before initiating treatment for mildly
is preferred for patients with thoracic symptoms or residual masses or elevated beta-hCG (generally <20 IU/L) as other factors such as
nodules in the chest. Patients with residual masses may require more hypogonadism and marijuana use can cause false-positive results.

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NCCN Guidelines Version 2.2024

Testicular Cancer

Elevations of AFP either pre- or post-orchiectomy indicate the presence of Patients with clinical stage I pure teratoma and normal markers should
nonseminomatous elements. For patients with elevated beta-hCG levels receive either surveillance or RPLND. Stage II disease may be treated
pre-orchiectomy, beta-hCG levels should be followed with repeated with systemic therapy or RPLND. Systemic therapy is preferred if serum
determinations after orchiectomy to determine their trajectory and, if tumor markers are elevated and/or if the enlarged lymph nodes are >3
declining, their nadir. The expected half-life for beta-hCG is ≤3 days. For cm in greatest dimension. RPLND is preferred as primary treatment for
patients with normal imaging (ie, stage I), rising or persistently elevated stage II tumors with somatic-type malignancy (previously referred to as
beta-hCG levels generally indicate the presence of metastatic disease transformed teratoma), and should be considered for stage II tumors with
(stage IS). Beta-hCG levels >1000 IU/L may indicate the presence of non- teratoma predominance if serum tumor markers are normal. Stage II and
seminomatous tumor elements. Sperm banking should be recommended stage III disease treated with systemic chemotherapy should be followed
to patients of reproductive age, if clinically indicated, before undergoing by surgical resection of any residual masses.
any therapeutic intervention that may compromise fertility.40-43
Nonseminoma Stage I Without Risk Factors
Treatment options for clinical stage I nonseminoma after inguinal
orchiectomy include surveillance, adjuvant systemic therapy, and primary Primary Treatment for Nonseminoma Stage I Without Risk Factors
RPLND. A template dissection or nerve-sparing approach to minimize The NCCN Panel recommends treating patients with stage I
the risk of ejaculatory disorders should be considered in patients nonseminoma based on the presence or absence of risk factors known to
undergoing primary RPLND for stage I nonseminoma. The “split and roll” be associated with an increased risk of relapse (LVI, invasion of the
technique in which lumbar vessels are identified and sequentially ligated spermatic cord, or invasion of the scrotum).47-55 Some centers also
allows resection of all lymphatic tissue around and behind the great consider predominance of embryonal carcinoma as an additional risk
vessels (ie, aorta, inferior vena cava) and minimizes the risk of an in-field factor for relapse. Additionally, the Panel recommends staging tumors with
recurrence. Limited data suggest increased frequency of aberrant discontinuous invasions of the spermatic cord as pT3 (high-risk stage I)
recurrences with the use of minimally invasive laparoscopic or robotic and not as M1 (stage III) as is recommended in the 8th edition of the AJCC
approaches to RPLND. A recent case study of recurrence patterns in Cancer Staging Manual. It is critical to remember that risk of relapse to the
patients following robotic RPLND found that recurrences were highly pelvis is higher in these patients. However, regardless of risk factors,
variable, were in unusual locations, and were associated with a high patients with stage I nonseminoma with normal post-orchiectomy serum
treatment burden.148 However, two retrospective reviews on robotic AFP and beta-hCG levels have three management options after
RPLND done at experienced centers showed that this technique can be orchiectomy: surveillance,52,60,151,152 nerve-sparing RPLND,153 or adjuvant
performed safely with low complication rates and similar oncologic chemotherapy (one cycle of BEP)154,155 as primary treatment. The major
outcomes to an open approach.149,150 Therefore, minimally invasive difference in the treatment of patients at low risk and high risk is that
RPLND is not currently recommended as standard management, but can surveillance is preferred for patients with stage I nonseminoma without risk
be considered in highly selected cases at high-volume centers. factors, whereas all three management options should be carefully
considered when risk factors are present. The survival rates for stage I

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NCCN Guidelines Version 2.2024

Testicular Cancer

nonseminoma managed with surveillance, nerve-sparing RPLND, or one assessment, abdomen/pelvis CT scan with contrast or MRI with and
cycle of BEP chemotherapy exceed 98%. However, the high survival rate without contrast, and chest x-ray. The frequency of these tests varies with
associated with surveillance depends on adherence to periodic follow-up the primary treatment modality received by the patient (see Tables 6 and 8
examinations and subsequent chemotherapy for the 20% to 30% of on TEST-B in the algorithm). The MRI protocol should include visualization
patients who relapse. Therefore, patients who choose surveillance should of the retroperitoneal and pelvis nodes as well as all other nodes that need
adhere to the follow-up schedule. When nerve-sparing RPLND is to be assessed. Chest CT with contrast is preferred over chest x-ray in the
performed, it should be done within 4 weeks of a CT scan and within 7 to presence of thoracic symptoms for patients regardless of treatment type. It
10 days of repeat serum marker testing to ensure accurate presurgical should be noted that routine chest x-ray may have limited value for
staging.156 Referral to a high-volume center is recommended for nerve- detecting relapse in patients with stage I nonseminoma. In a recent
sparing RPLND. Similarly, for patients electing one cycle of BEP, imaging retrospective study, a total of 76 relapses were detected among 561
is recommended within 4 weeks prior to the initiation of chemotherapy to patients with stage I nonseminoma treated with surveillance following
confirm staging, even if scans were done previously. orchiectomy.112 All relapses were detected by either rising serum tumor
markers and/or abnormal routine follow-up CT scans; no single relapse
Management of Nonseminoma Stage I Without Risk Factors After RPLND was detected by chest x-ray alone. Similar results have been reported in
If the resected lymph nodes are negative for malignancy (pN0) after nerve- other studies, calling into question the value of chest x-rays in surveillance
sparing RPLND, the patient should undergo surveillance. For positive settings for stage I nonseminomatous GCTs.60,113,159
lymph nodes (pN1 to pN3), the decision of whether to use adjuvant
chemotherapy is based on the degree of nodal involvement. Surveillance Nonseminoma Stage I With Risk Factors
is the preferred option for patients with pN1 disease, while chemotherapy Primary Treatment for Nonseminoma Stage I With Risk Factors
is the preferred option for patients with pN2 disease (surveillance is
Surveillance, adjuvant chemotherapy (one cycle of BEP), or nerve-sparing
preferred for patients with pure teratoma). Chemotherapy is also the
RPLND are the recommended primary treatment options for patients with
preferred option for patients with pN3 disease. Recommended
stage I nonseminoma with LVI, invasion of the spermatic cord, or invasion
chemotherapy regimens include two cycles of EP (preferred) for patients
of the scrotum. Referral to a high-volume center is recommended for
with pN1 or pN2 disease157,158 and three cycles of BEP or four cycles of
nerve-sparing RPLND. In a prospective trial by SWENOTECA, patients
EP (both preferred) for patients with pN3 disease. While rare, BEP for two
with stage I nonseminoma with or without LVI received one course of
cycles can also be an option for pN3. Additionally, a bleomycin-free
adjuvant BEP.155 The relapse rate at 5 years was 3.2% for patients with
regimen in patients at enhanced risk for bleomycin toxicity, such as those
LVI and 1.6% for patients without LVI. Five-year OS was 100% in both
with reduced GFR or older age, should be considered.
groups.47 The results after a median follow-up of 7.9 years confirmed the
Follow-up for Nonseminoma Stage I Without Risk Factors
low relapse rate with one course of adjuvant BEP, especially in patients
with LVI.47 Several other studies using two cycles of BEP as primary
The long-term follow-up for patients with stage I nonseminoma without risk treatment for patients with stage I nonseminoma have similarly reported
factors includes a history and physical examination, serum tumor marker

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NCCN Guidelines Version 2.2024

Testicular Cancer

relapse-free survival rates of >95%.152,158,160-163 However, late Nonseminoma Stage IS

consequences of cisplatin-based chemotherapy, such as hearing damage
Patients with stage IS nonseminoma exhibit persistent elevation of serum
and loss, cardiovascular conditions, hypertension, and neuropathy, have
tumor markers post-orchiectomy, but no radiographic evidence of disease.
been reported during long-term follow-up.164-172 Therefore, one cycle of
However, mildly elevated levels of AFP or beta-hCG after orchiectomy
BEP is recommended due to its lower toxicity. Surveillance is also a
must be interpreted with caution. Mildly elevated, non-rising AFP levels
recommended primary treatment option for patients with stage I
(<20 ng/mL) may not indicate the presence of a GCT and should not be
nonseminoma with risk factors. However, it should be noted that LVI is a
used to guide treatment decisions. In addition, hyperthyroidism, marijuana
significant predictor of relapse when orchiectomy is followed by
use, hypogonadism, and heterophile antibodies can result in significant
surveillance alone.34
elevations of beta-hCG.22-24,26,27 Elevated beta-hCG due to metastatic
Management of Nonseminoma Stage I With Risk Factors After RPLND
disease typically rises steadily on serial measurements. In patients with
mildly elevated but stable beta-hCG and no other evidence of metastatic
The treatment of patients with stage I nonseminoma with risk factors after disease, repeating the test using a different assay should be considered.
primary RPLND is similar to that of patients with stage I nonseminoma Furthermore, many different conditions can result in an elevation of LDH,
without risk factors, as described above. including many benign conditions. Therefore, patients should not be
treated with chemotherapy for systemic disease if the only evidence of
Follow-up for Nonseminoma Stage I With Risk Factors
systemic disease is an elevation of LDH.
The long-term follow-up for patients with stage I nonseminoma with risk
factors under active surveillance includes history and physical examination Primary Treatment for Nonseminoma Stage IS
with serum tumor marker assessment on the same schedule as that for The NCCN Panel recommends that patients with stage IS nonseminoma
patients with stage I nonseminoma without risk factors as described be treated with first-line chemotherapy if the elevated marker is AFP or
above. Abdomen/pelvis CT scan with contrast or MRI with and without beta-hCG. For the purposes of this guideline, the NCCN Panel assumes
contrast as well as chest x-ray are recommended, and the MRI protocol that patients with stage IS disease have markers in the S1 range. It would
should include visualization of the retroperitoneal and pelvic nodes. Chest be extraordinarily rare for a patient to have an AFP >1000 ng/mL or a
x-ray may be used for routine follow-up, but chest CT with contrast is beta-hCG >5000 IU/L and yet have no evidence of metastatic disease on
preferred in patients with thoracic symptoms. In patients treated with one imaging studies. These guidelines cannot address every possible
cycle of adjuvant BEP chemotherapy or primary RPLND, follow-up is the situation, and the treatment of those rare patients with T any, N0, M0, S2–
same as described above for patients with clinical stage I nonseminoma 3 disease should be individualized; referral to a high-volume center is
without risk factors. recommended. The vast majority of patients with stage IS have serum
tumor markers in the S1 range, and they should receive first-line
chemotherapy for good-risk disease: either three cycles of BEP or four
cycles of EP (both preferred). Both regimens are category 1

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NCCN Guidelines Version 2.2024

Testicular Cancer

recommendations, and either is preferable to initial RPLND as these Management of Nonseminoma Stage IIA After Primary Treatment
patients nearly always have disseminated disease.173,174 Treatment options following primary nerve-sparing RPLND include either
surveillance or chemotherapy, depending on the number of positive lymph
Management of Nonseminoma Stage IS After Primary Treatment
nodes identified. Since RPLND is likely a curative procedure in patients
The treatment of patients with stage IS nonseminoma after primary with pN0 disease, surveillance is recommended for this group.
treatment with chemotherapy is described below in Advanced Metastatic Surveillance is also the preferred option for patients with pN1 disease,
Nonseminoma (see Management of Good-, Intermediate-, and Poor-Risk although chemotherapy with two cycles of EP can also be
Nonseminoma After Chemotherapy). considered.153,178 The risk of relapse in clinical stage IIA nonseminoma
patients with pN2 or pN3 disease after RPLND is >50%.153,179 This risk is
Nonseminoma Stage IIA
reduced to <1% with two cycles of adjuvant cisplatin-based
Primary Treatment for Nonseminoma Stage IIA chemotherapy.153,180,181 Therefore, the NCCN Panel prefers two cycles of
Primary treatment for patients with stage IIA nonseminoma depends on adjuvant chemotherapy with EP to surveillance for pN2 disease and
post-orchiectomy serum tumor marker levels. For select cases of clinical recommends full-course chemotherapy for pN3 disease (either three
stage IIA disease with borderline retroperitoneal lymph nodes, waiting 4 cycles of BEP or four cycles of EP; both preferred). For patients with
weeks and repeating imaging to confirm staging before initiating treatment pathologic stage II nonseminoma, two cycles of BEP is an alternative
can be considered. For patients with normal post-orchiectomy levels of option for those with pN3 disease following primary RPLND.182 A
AFP and beta-hCG, the NCCN Panel recommends either nerve-sparing bleomycin-free regimen should be given to patients at higher risk for
RPLND or chemotherapy with three cycles of BEP or four cycles of EP as bleomycin-related complications (ie, patients aged >50 years, those with
primary treatment options (both BEP and EP are preferred diminished renal function, and those with underlying lung disease).
regimens).175,176 Chemotherapy is considered particularly appropriate if the Surveillance is preferred for patients with pure teratoma.
patient has multifocal disease. RPLND is preferred as primary treatment Subsequent management after first-line chemotherapy depends on the
for stage II tumors with somatic type malignancy (previously referred to as size of the residual mass on CT scan. Patients should thus undergo
transformed teratoma). Referral to a high-volume center is recommended abdomen/pelvis CT scan with contrast or MRI with and without contrast
for nerve-sparing RPLND. For patients with stage IIA seminoma with within 1 month of completing chemotherapy; chest CT with contrast or
persistently elevated AFP and/or beta-hCG levels, the NCCN Panel chest x-ray may also be considered. FDG-PET/CT scan is not clinically
recommends first-line chemotherapy with three cycles of BEP or four indicated for nonseminoma. Masses should be measured along the
cycles of EP (both category 1; both preferred).153,177 A bleomycin-free transaxial long axis (not the craniocaudal axis). If the residual mass is ≥1
regimen should be given to patients at higher risk for bleomycin-related cm after chemotherapy, nerve-sparing bilateral RPLND is recommended.
complications (ie, patients aged >50 years, those with diminished renal A bilateral RPLND involves removal of lymphatic tissue between both
function, and those with underlying lung disease, etc). ureters, spanning from the diaphragmatic crus to the bifurcation of the
common iliac arteries. The rationale for this extended region of dissection

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NCCN Guidelines Version 2.2024

Testicular Cancer

is the greater likelihood of bilateral disease with greater tumor burden.183 This follow-up schedule is optional in patients treated with primary
Modified template RPLND may be an option in select patients with initial RPLND. Additionally, patients with clinical stage II disease treated with
stage IIA/B disease within the primary landing zones. The major morbidity chemotherapy who undergo postchemotherapy RPLND and are found to
associated with bilateral RPLND is retrograde ejaculation, resulting in have pN0 disease or pN1 pure teratoma need only 1 CT scan at
infertility. Nerve-sparing dissection techniques preserve antegrade postoperative month 3 or 4 and then as clinically indicated.
ejaculation in 90% of cases.184 Therefore, nerve-sparing RPLND is
recommended. For patients with no residual mass or a residual mass <1 Nonseminoma Stage IIB
cm, surveillance is recommended; nerve-sparing bilateral RPLND is a Primary Treatment for Nonseminoma Stage IIB
category 2B recommendation in this setting and may be performed in
Primary treatment for patients with stage IIB nonseminoma depends on
selected cases. Referral to a high-volume center is recommended for
post-orchiectomy tumor marker levels and radiographic findings. When
surgical resection of masses post-chemotherapy. If only necrotic debris or
tumor marker levels are normal, the CT findings determine the proper
teratoma is present in the resected tissue, the patient should be put under
course of treatment. If abnormal radiographic findings are limited to lymph
surveillance. If embryonal, yolk sac, choriocarcinoma, or seminoma
node metastases within lymphatic drainage sites in the retroperitoneum
elements are found in the residual mass, then two cycles of chemotherapy
(ie, the landing zone), patients may receive first-line chemotherapy with
with either TIP, VIP, VelP, or EP is recommended. Surveillance could be
either three cycles of BEP or four cycles of EP (both preferred) or primary
considered as a reasonable alternative to chemotherapy for patients with
nerve-sparing RPLND (reserved for highly selected cases; ie, stage II
residual masses that have been completely resected if all of the residual
tumors with teratoma predominance in patients with normal markers).
masses have <10% viable cancer cells in the resected tissue.
RPLND is also recommended for stage II tumors with somatic type
Follow-up for Nonseminoma Stage IIA malignancy (previously referred to as transformed teratoma). Referral to a
high-volume center is recommended for nerve-sparing RPLND. Both
The 5-year follow-up for patients with stage IIA nonseminoma includes
options of first-line chemotherapy or primary nerve-sparing RPLND are
history and physical examinations, serum tumor marker assessments,
comparable in terms of outcome, but side effects and toxicity are
chest x-rays, and abdomen/pelvis CT scans. An MRI can be considered to
different.176 The reported relapse-free survival with either approach is
replace an abdomen/pelvis CT. The MRI protocol should include
close to 98%.179-181,186,187 If metastatic disease (based on radiographic
visualization of the retroperitoneal and pelvis nodes. All imaging in this
findings) is not confined to within the lymphatic drainage sites (ie,
setting is performed with contrast. The frequency of these tests varies with
multifocal or symptomatic lymph node metastases with aberrant lymphatic
the primary treatment modality and post-surgical treatment received by the
drainage sites), first-line chemotherapy (three cycles of BEP or four cycles
patient (see Tables 9 through 11 on TEST-B in the algorithm). Chest x-ray
of EP; both preferred) is recommended. For patients with stage IIB
may be used for routine follow-up, but chest CT with contrast is preferred
nonseminoma with persistent marker elevation, the recommended
in patients with thoracic symptoms. Annual measurement of serum tumor
treatment option is also first-line chemotherapy with either three cycles of
markers can be considered for years 5 through 10 following complete
BEP or four cycles of EP (both category 1; both preferred). A bleomycin-
response to first-line chemotherapy in patients with metastatic disease.185

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NCCN Guidelines Version 2.2024

Testicular Cancer

free regimen should be given to patients at higher risk for bleomycin- Primary Treatment for Good-Risk Nonseminoma
related complications (ie, patients aged >50 years, those with diminished The IGCCCG good-risk group includes patients with stages IS, IIA (S1),
renal function, and those with underlying lung disease). IIB (S1), IIC, and IIIA disease. The treatment goal for good-risk disease is
to limit toxicity while maintaining maximal efficacy. Presently, two
Management of Nonseminoma Stage IIB After Primary Treatment
regimens are recommended by the NCCN Panel: three cycles of
The treatment of patients with stage IIB nonseminoma after primary BEP125,127,188 or four cycles of EP126,127,188 (both category 1; both preferred).
treatment with either nerve-sparing RPLND or chemotherapy is similar to Both regimens are well tolerated and cure approximately 90% of patients
the post-primary treatment scheme outlined above for patients with stage with good-risk disease.188,189 The only trial that directly compared these
IIA nonseminoma (see Management of Nonseminoma Stage IIA After two regimens found no statistically significant difference in OS (96% in the
Primary Treatment). BEP x 3 arm vs. 92% in the EP x 4 arm; P = .096) or event-free survival
(91% with BEP x 3 vs. 86% with EP x 4; P = .135).188 Factors that should
Follow-up for Nonseminoma Stage IIB
be considered when choosing between three cycles of BEP and four
The 5-year follow-up schedule for patients with stage IIB nonseminoma is cycles of EP include the duration of treatment (9 weeks compared to 12
similar to the follow-up schedule outlined above for patients with stage IIA weeks) and regimen-specific toxicities (bleomycin is associated with
nonseminoma and is dependent on the primary treatment modality and reduced pulmonary function while cisplatin is associated with peripheral
post-surgical treatment received by the patient (see Follow-up for neuropathy and hearing loss). The physician and patient should make a
Nonseminoma Stage IIA and Tables 9 through 11 on TEST-B in the shared informed decision based on patient clinical characteristics and
algorithm). Additionally, patients with clinical stage IIA or IIB who undergo preferences. A bleomycin-free regimen should be given to patients at
primary RPLND and are found to have pN0 disease should revert to the higher risk for bleomycin-related complications (ie, patients aged >50
surveillance schedule for low-risk NSGCT with the exception that only 1 years, those with diminished renal function, and those with underlying lung
CT scan is needed postoperatively around month 4. disease). Some oncologists prefer four cycles of EP for heavy smokers
regardless of lung function.
Advanced Metastatic Nonseminoma
Primary Treatment for Intermediate-Risk (Stage IIIB) Nonseminoma
The first-line chemotherapy options for patients with advanced metastatic
nonseminoma are based on the IGCCCG risk classification, which For patients with intermediate-risk disease, the cure rate is approximately
categorizes patients as good, intermediate, or poor risk based on 70% with the standard chemotherapy regimen of four cycles of BEP.190,191
identification of clinically independent prognostic features such as extent Therefore, the NCCN Panel recommends four cycles of BEP (preferred),
of disease and post-orchiectomy levels of serum tumor markers.68 When or four cycles of VIP190,192 for patients who are at higher risk for bleomycin-
determining a patient’s risk classification, the relevant serum tumor marker related complications, for the treatment of intermediate-risk (stage IIIB)
value is the value on day 1 of cycle one of first-line chemotherapy. nonseminoma. Both regimens are category 1 recommendations. However,

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NCCN Guidelines Version 2.2024

Testicular Cancer

if intermediate-risk status is based solely on LDH levels 1.5 to 3 × ULN, Nerve-sparing bilateral RPLND can be considered in select cases for
then three cycles of BEP or four cycles of EP193 can be considered. patients who had retroperitoneal lymphadenopathy prior to chemotherapy
(category 2B).196 RPLND is recommended within 4 weeks of the CT scan
Primary Treatment for Poor-Risk (Stage IIIC) Nonseminoma and 7 to 10 days of marker measurement. Referral to high-volume centers
The standard chemotherapy regimen for poor-risk disease is four cycles of is recommended for surgical resection of residual masses following
BEP (preferred). Alternatively, four cycles of VIP can be used to treat chemotherapy.
patients who are at higher risk for bleomycin-related complications.192 Both If there is a partial radiographic response to chemotherapy (as indicated
regimens are category 1 recommendations. However, <50% of patients by the presence of residual masses) and tumor marker levels are normal,
with poor-risk nonseminoma experience a durable complete response to then surgical resection of all residual masses is recommended.197-200 As
four cycles of BEP, and up to 50% die of their disease.68,194 Therefore, previously stated, referral to high-volume centers is recommended for
referral to a high-volume center is recommended for the treatment of surgical resection of masses post-chemotherapy. If only necrotic debris or
patients with poor-risk nonseminoma.189 teratoma is present in the resected tissue, the patient should be put under
A recent randomized phase II trial compared the efficacy of four cycles of surveillance. If embryonal, yolk sac, choriocarcinoma, or seminoma
BEP to a more intensive regimen (carboplatin, bleomycin, vincristine, and elements are found in the residual mass, then two cycles of chemotherapy
cisplatin/BEP [CBOP/BEP]) in 89 patients with poor-risk nonseminoma.195 with either EP, TIP, VIP, or VelP should be administered. All regimens are
At a median follow-up of 63 months, 3-year PFS was 56% for CBOP/BEP preferred in this setting, although EP should be considered for patients
and 39% for BEP (HR, 0.59; P = .079). Three-year OS was 65% and 59%, with low-volume residual disease. If there is a teratoma with somatic-type
respectively (HR, 0.79; P = .49), and there were no differences in toxicity malignancy, consider histology-directed therapy and referral to a high-
between arms. The CBOP/BEP met response targets (74% complete volume center.
response or partial response with negative markers) and warrants further Further treatment for patients who experience a partial radiographic
study in a phase III trial. response to chemotherapy (residual masses) with abnormal tumor marker
levels is guided by the kinetics of the tumor markers. If tumor marker
Management of Good-, Intermediate-, and Poor-Risk Nonseminoma After
Chemotherapy
levels are elevated and persistently rising, the Panel recommends a full
course of second-line chemotherapy (see Second-Line Therapy below).
At the conclusion of first-line chemotherapy, chest/abdomen/pelvis CT Brain imaging and testicular ultrasound should be considered in patients
scan with contrast/MRI with and without contrast and measurement of with elevated or rising markers following first-line or second-line
serum tumor marker levels are indicated to assess treatment response. chemotherapy to evaluate for occult brain metastases or contralateral
FDG-PET scan has no role in assessing treatment response and residual primary disease. Patients with elevated but stable marker levels should be
masses following chemotherapy in patients with nonseminoma. If a closely surveilled. Patients with mildly elevated and normalizing markers
complete response to chemotherapy is found by radiographic imaging and should be considered for surgical resection of residual masses with
the tumor marker levels are normal, the Panel recommends surveillance. subsequent post-surgical treatment as discussed above. The Panel

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NCCN Guidelines Version 2.2024

Testicular Cancer

recommends referral to a high-volume center for the treatment of patients chemotherapy as previously discussed is recommended. It is preferred by
with a partial response to first-line chemotherapy and abnormal marker the Panel that patients with recurrent seminoma or nonseminoma be
levels. treated at centers with expertise in the management of this disease.
Second-line therapy options for patients with relapsed seminoma or early
Follow-up for Good-, Intermediate-, and Poor-Risk Nonseminoma relapses (within 2 years of the completion of primary therapy) of
The 5-year follow-up for patients with good-, intermediate-, and poor-risk nonseminoma include enrollment in a clinical trial (preferred),
nonseminoma after chemotherapy (with or without post-chemotherapy conventional-dose chemotherapy, or high-dose chemotherapy. If
RPLND) includes history and physical examination, serum tumor marker chemotherapy is given, both conventional-dose and high-dose regimens
assessment, chest x-ray, and abdomen/pelvis CT scan. The frequency of are preferred in this setting. The conventional-dose regimens are TIP or
these tests is outlined in Table 9 on TEST-B 2 of 3. Annual measurement VeIP, both of which are high risk for febrile neutropenia so G-CSFs should
of serum tumor markers can be considered for years 5 through 10 be used.141,201-203 The high-dose regimens include high-dose carboplatin
following complete response to first-line chemotherapy in patients with plus etoposide followed by autologous stem cell transplant,204 or paclitaxel
metastatic disease.185 Patients who have an incomplete response to plus ifosfamide followed by high-dose carboplatin plus etoposide with stem
chemotherapy require more frequent imaging than is outlined in the table. cell support.205 Alternatively, surgical salvage may be considered for
Patients who undergo RPLND and are found to have pN0 disease or pN1 nonseminoma if the recurrent mass is in a solitary resectable site.206 Late
pure teratoma need only one CT scan at postoperative months 3 to 4 and relapses (>2 years after completion of first-line therapy) occur in 2% to 3%
then as clinically indicated. An MRI can be considered to replace an of testicular cancer survivors.207,208 The Panel prefers surgical salvage for
abdomen/pelvis CT, and the MRI protocol should include all the nodes that these patients, if the recurrent mass is resectable.206 Clinical trial
need to be assessed. All imaging in this setting is performed with contrast. enrollment or chemotherapy (conventional-dose or high-dose) are options
Chest x-ray may be used for routine follow-up, but chest CT with contrast for patients with unresectable late relapses.
is preferred in patients with thoracic symptoms. An ongoing, randomized, international phase III trial (TIGER) will compare
second-line conventional-dose chemotherapy with high-dose
Second-Line and Subsequent Therapy for Metastatic chemotherapy in patients with relapsed GCTs.209 The foundation of the
Germ Cell Tumors TIGER trial was formed based on the results of a large retrospective
Second-Line Therapy analysis by Lorch et al, which demonstrated the superiority of carboplatin-
based high-dose chemotherapy compared to cisplatin-based conventional-
Patients with disease relapse following first-line therapy, or those who do dose chemotherapy with respect to 2-year progression-free survival (50%
not experience a durable complete response to first-line therapy, should vs. 28%; P < .001) and 5-year OS (53% vs. 41%; P < .001).210,211 The
receive second-line therapy. Patients with recurrent disease who have not TIGER trial will randomize patients with unequivocal disease progression
been treated with prior chemotherapy should be treated per their risk following cisplatin-based first-line chemotherapy to receive conventional-
status, as described in the preceding sections. Additionally, if a patient dose TIP or high-dose paclitaxel plus ifosfamide followed by high-dose
received prior adjuvant therapy (ie, one cycle of BEP only), first-line

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NCCN Guidelines Version 2.2024

Testicular Cancer

carboplatin plus etoposide with stem cell support. OS is the primary considered for surgical resection of residual masses followed by
endpoint. Secondary endpoints include progression-free survival, surveillance. Referral to high-volume centers is recommended for surgical
response rate, toxicity, quality of life, and biological correlates.209,210 This resection of residual masses following chemotherapy.
trial has completed patient recruitment and results are expected sometime
in the near future (Clinical Trial ID: NCT02375204). Third-Line Therapy
Participation in a clinical trial is the preferred treatment option for patients
Management of Metastatic Germ Cell Tumors After Second-Line Therapy
who experience relapse following first- and second-line therapy.
To assess response after second-line therapy, a CT scan with contrast or Alternatively, patients previously treated with conventional-dose
MRI with and without contrast of the chest, abdomen, pelvis, and any chemotherapy can receive high-dose regimens or, with nonseminoma, be
other sites of disease is recommended. FDG-PET scan has no role in considered for surgical salvage if the recurrent mass is in a solitary
assessing treatment response and residual masses following resectable site. Additionally, select patients with seminoma can be treated
chemotherapy in patients with nonseminoma but could be considered in with RT. Alternative options for patients previously treated with high-dose
assessing treatment response and residual masses following regimens include conventional-dose salvage chemotherapy, surgical
chemotherapy in patients with seminoma. Levels of serum tumor markers salvage (if solitary resectable site) for nonseminoma, RT in select patients
should also be measured. For patients with seminoma, follow-up is similar with seminoma, and microsatellite instability/mismatch repair (MSI/MMR)
to post first-line chemotherapy treatment. Patients with nonseminoma that or tumor mutation burden (TMB) testing, if disease progresses after high-
demonstrate a complete response to second-line therapy with normal dose chemotherapy or third-line therapy. The preferred treatment option
marker levels should be put under surveillance. Alternatively, select for patients with nonseminoma who experience a late relapse (>2 years
patients with nonseminoma may receive nerve-sparing bilateral RPLND after completion of second-line therapy) is surgical salvage, if the recurrent
(category 2B), followed by surveillance. Referral to a high-volume center is mass is resectable. Conventional-dose or high-dose chemotherapy (if not
recommended for nerve-sparing RPLND. For patients with nonseminoma previously received) are also options for patients with late relapse.
and a partial response to second-line therapy (as indicated by residual
In order to maintain optimal efficacy and limit treatment-related toxicities,
masses on CT scan) and normal marker levels, surgical resection of all
the chemotherapy regimens previously received by the patient should be
residual masses is recommended followed by surveillance. If there is a
considered when deciding on third-line therapy options. High-dose
teratoma with somatic-type malignancy, consider histology-directed
chemotherapy is the preferred third-line option if it has not been previously
therapy and referral to a high-volume center. Patients with a partial
received. If high-dose chemotherapy was previously received by the
response to second-line therapy (residual masses) and abnormal marker
patient, then palliative chemotherapy is the preferred third-line treatment
levels should be treated according to the kinetics of the tumor markers. If
option. Additionally, the Panel considers pembrolizumab immunotherapy
tumor marker levels are elevated and persistently rising, the Panel
to be useful in certain circumstances (ie, in patients with MSI-high/deficient
recommends third-line therapy (see Third-Line Therapy below). Patients
MMR [MSI-H/dMMR] or tumor mutation burden-high [TMB-H, ≥10
with elevated but stable tumor marker levels should be closely surveilled.
Patients with mildly elevated and normalizing markers should be

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NCCN Guidelines Version 2.2024

Testicular Cancer

mutations/megabase] tumors as determined by a validated an/or U.S. Two patients achieved stable disease for 28 and 19 weeks, respectively,
Food and Drug Administration [FDA]-approved CGP assay).212-215 but no partial or complete responses were observed. There were six grade
3 adverse events, but no immune-related adverse events were reported.
The recommended third-line palliative chemotherapy options for patients
Therefore, pembrolizumab was well tolerated but appears to have limited
with intensively pretreated, cisplatin-resistant, or refractory GCTs are
single-agent activity in refractory GCTs. However, larger phase II and
combinations of gemcitabine with paclitaxel and/or oxaliplatin,216-222 or oral
phase III trials of pembrolizumab in patients with metastatic or refractory
etoposide.223 The recommendation for gemcitabine and oxaliplatin
testicular cancers are needed to fully assess the value of this therapy,
(GEMOX) is based on data from phase II studies investigating the efficacy
especially in treating MSI-H/dMMR or TMB-H testicular GCTs.
and toxicity of GEMOX in patients with relapsed or cisplatin-resistant
GCTs.217,219,221 These studies showed that GEMOX is safe for patients
Treatment of Brain Metastases
with cisplatin-resistant testicular GCTs and may offer a chance of
long-term survival.217,219,221 Gemcitabine and paclitaxel is another option Brain metastases from testicular GCTs are relatively rare and occur
that has shown promising results in a phase II study.218 Follow-up results almost exclusively in patients with nonseminoma histology.227 The
showed long-term disease-free survival in patients who progressed after development of brain metastases may be more common in patients with a
high-dose chemotherapy and had not received prior paclitaxel or higher burden of systemic disease; lung, liver, and/or bone metastases;
gemcitabine.220 A phase II study of patients with treatment-resistant GCTs high levels of serum beta-hCG (>5000 IU/L); in those with neurologic
also found the combination of gemcitabine, oxaliplatin, and paclitaxel to be symptoms; and in those who experience relapse after cisplatin-based
effective with acceptable toxicity.216 The overall response rate was 51% chemotherapy. The prognosis of patients with brain metastases from
with 5% of patients achieving a complete response. A second study testicular GCTs is poor, with >50% of patients dying within 1 year of
reported similar results.222 Additionally, high-dose single-agent oral diagnosis.227,228 Patients with additional adverse prognostic factors,
etoposide was shown to be effective in a phase II study involving patients especially those with metachronous brain metastases, have even worse
who had previous treatment with cisplatin/etoposide combination outcomes.227,229,230
regimens.223
In a recent retrospective analysis, Loriot et al reported on the pattern of
Pembrolizumab, an anti-programmed cell death protein 1 (PD-1) antibody, relapse among patients with poor-risk nonseminomatous GCTs previously
is approved by the FDA for the treatment of patients with unresectable or treated with chemotherapy.231 After a median follow-up of 4.1 years, 32%
metastatic MSI-H/dMMR or TMB-H solid tumors that have progressed were found to have radiographic evidence of brain metastases. The brain
following prior treatment and who have no satisfactory alternative was the only site of progression in 54% of these patients and 19%
treatment options.212,213,215,224,225 In the only trial (phase II) investigating the experienced progression in the brain as the first progression event.
efficacy of immunotherapy in testicular cancer, 12 patients with Furthermore, involvement of the brain was more common among patients
nonseminoma GCTs who progressed after first-line cisplatin-based who were previously treated with high-dose chemotherapy (29%)
therapy and greater than or equal to one salvage regimen (high-dose or compared to BEP (12%). These data suggest that brain metastases from
conventional-dose chemotherapy) were treated with pembrolizumab.226 testicular GCTs may occur more frequently than previously thought, often

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NCCN Guidelines Version 2.2024

Testicular Cancer

as the only site of progression, and may be more likely to occur in patients treatment if feasible. RPLND should be considered in patients with stage I
at poor risk previously treated with high-dose chemotherapy. However, it is disease who have teratoma with malignant transformation in their primary
unknown whether this effect was due to the lower cerebral drug tumor in order to eradicate any microscopic retroperitoneal metastases
penetrance of the high-dose regimen. and reduce the risk of relapse. For patients with more advanced disease
(stage II or III), complete surgical resection if feasible is preferred. For
The optimal management of brain metastases from testicular GCTs is
patients with unresectable disease, histology-specific chemotherapy
controversial, with a lack of evidence from prospective trials to guide
should be considered.
treatment decisions.227,229 Therefore, management decisions are usually
based on institutional preferences, which may in part explain the large Malignant transformation of teratoma along mesodermal lines results in a
variation in treatment modalities received by these patients. The NCCN primitive small round blue cell tumor referred to as embryonic-type
Guidelines recommend first-line cisplatin-based chemotherapy neuroectodermal tumor (ENT).237 This was previously termed primitive
(chemotherapy for poor-risk disease) for patients with brain metastases. neuroectodermal tumor (PNET) arising from teratoma. The preferred
The addition of RT to chemotherapy regimens can also be considered.232 modality of therapy for malignant transformation of teratoma to ENT is also
Surgical resection of metastatic brain lesions should be performed if surgical resection. ENT transformed from teratoma is resistant to cisplatin-
clinically indicated and feasible. A recent retrospective analysis reported based chemotherapy. Chemotherapy directed to ENT histology is
the treatment of 25 patients with relapsed GCTs and progressive brain associated with objective response. The preferred regimen consists of
metastases who received multimodality therapy, which included high-dose cyclophosphamide, doxorubicin, vincristine (CAV) alternating with
chemotherapy with stem cell support alone or combined with surgery ifosfamide plus etoposide (IE).238 For patients with stage I disease with
and/or stereotactic or whole-brain RT.233 At a median follow-up of 24.5 ENT histology, RPLND should be considered. If ENT histology is present
months, 44% of patients were alive with no evidence of disease, in surgical resection specimen, adjuvant chemotherapy with CAV
suggesting that this subset of patients with historically poor prognosis can alternating with IE for a total of four cycles should be considered. 238,239
potentially be cured with this approach. Rarely, GCTs may originate in extragonadal sites (usually the
retroperitoneum or mediastinum). Patients with an extragonadal primary
Malignant Transformation of Teratoma site are treated similarly to patients with testicular GCTs regarding
systemic therapies and management of residual masses.240 However, due
Teratoma is a pluripotent tissue that has the capacity to dedifferentiate into
to their rarity, the NCCN Panel recommends that patients with
somatic malignancies. Sarcomas or carcinomas arising from teratoma are
extragonadal GCTs be referred to high-volume centers with experience in
generally resistant to chemotherapy and are associated with poor
managing these tumors.
prognosis.56,234-236 Somatic transformation of teratoma is most frequently
seen in patients with metastatic disease who have been treated with
Summary
chemotherapy. However, this can occasionally be seen in patients who
have not received chemotherapy as well. Given the insensitivity of these The NCCN Guidelines for Testicular Cancer provide an evidence- and
tumors to systemic chemotherapy, surgical resection is the preferred consensus-based treatment approach for the treatment of adult patients

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NCCN Guidelines Version 2.2024

Testicular Cancer

with seminomatous and nonseminomatous testicular GCTs. Testicular

GCTs are sensitive to platinum-based chemotherapy and patients have
high cure rates even with metastatic disease. Although the majority of
metastatic testicular GCTs are cured with chemotherapy, 20% to 30% of
patients will relapse after first-line chemotherapy and require additional
treatment strategies. The ongoing international phase III TIGER trial aims
to determine whether high-dose or conventional-dose chemotherapy is
more effective in the second-line setting for patients with relapsed disease.
Patients with platinum-refractory or relapsing tumors after second-line
therapy have very poor outcomes despite salvage treatments with no
effective alternative therapies. Targeted therapies appear to have limited
activity in this setting, although more robust clinical trials are needed to
assess their value in treating testicular GCTs. Prognosis for patients with
brain metastases remains poor, with a lack of evidence from prospective
trials to guide treatment decisions. Therefore, the NCCN Panel
encourages patients with metastatic, recurrent, or platinum-refractory
testicular GCTs to participate in well-designed clinical trials investigating
novel therapeutic strategies to enable further advances for the
management of this disease.

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NCCN Guidelines Version 2.2024

Testicular Cancer

10. Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer Statistics, 2021. CA
References Cancer J Clin 2021;71:7-33. Available at:
1. Siegel RL, Giaquinto AN, Jemal A. Cancer statistics, 2024. CA Cancer J https://www.ncbi.nlm.nih.gov/pubmed/33433946.
Clin 2024;74:12-49. Available at: 11. Turnbull C, Rahman N. Genome-wide association studies provide new
https://www.ncbi.nlm.nih.gov/pubmed/38230766. insights into the genetic basis of testicular germ-cell tumour. Int J Androl
2. SEER Cancer Statistics Factsheets: Testicular Cancer. National Cancer 2011;34:e86-96; discussion e96-87. Available at:
Institute. Bethesda, MD. 2024. Available at: https://www.ncbi.nlm.nih.gov/pubmed/21623831.
https://seer.cancer.gov/statfacts/html/testis.html. Accessed June 12, 2024. 12. Greene MH, Kratz CP, Mai PL, et al. Familial testicular germ cell
3. Sarici H, Telli O, Eroglu M. Bilateral testicular germ cell tumors. Turk J tumors in adults: 2010 summary of genetic risk factors and clinical
Urol 2013;39:249-252. Available at: phenotype. Endocr Relat Cancer 2010;17:R109-121. Available at:
https://www.ncbi.nlm.nih.gov/pubmed/26328119. https://www.ncbi.nlm.nih.gov/pubmed/20228134.

4. Huyghe E, Matsuda T, Thonneau P. Increasing incidence of testicular 13. Vasdev N, Moon A, Thorpe AC. Classification, epidemiology and
cancer worldwide: a review. J Urol 2003;170:5-11. Available at: therapies for testicular germ cell tumours. Int J Dev Biol 2013;57:133-139.
https://www.ncbi.nlm.nih.gov/pubmed/12796635. Available at: https://www.ncbi.nlm.nih.gov/pubmed/23784823.

5. Shanmugalingam T, Soultati A, Chowdhury S, et al. Global incidence 14. Amin MB, Edge SB, Greene F, et al., eds. AJCC Cancer Staging
and outcome of testicular cancer. Clin Epidemiol 2013;5:417-427. Manual, 8th ed. New York: Springer International Publishing; 2017.
Available at: https://www.ncbi.nlm.nih.gov/pubmed/24204171. 15. Pierce JL, Frazier AL, Amatruda JF. Pediatric Germ Cell Tumors: A
6. Verhoeven RHA, Gondos A, Janssen-Heijnen MLG, et al. Testicular Developmental Perspective. Adv Urol 2018;2018:9059382. Available at:
cancer in Europe and the USA: survival still rising among older patients. https://www.ncbi.nlm.nih.gov/pubmed/29515628.
Ann Oncol 2013;24:508-513. Available at: 16. Wagner T, Scandura G, Roe A, et al. Prospective molecular and
https://www.ncbi.nlm.nih.gov/pubmed/23110807. morphological assessment of testicular prepubertal-type teratomas in
7. Chia VM, Quraishi SM, Devesa SS, et al. International trends in the postpubertal men. Mod Pathol 2020;33:713-721. Available at:
incidence of testicular cancer, 1973-2002. Cancer Epidemiol Biomarkers https://www.ncbi.nlm.nih.gov/pubmed/31695156.
Prev 2010;19:1151-1159. Available at: 17. Nazeer T, Ro JY, Amato RJ, et al. Histologically pure seminoma with
https://www.ncbi.nlm.nih.gov/pubmed/20447912. elevated alpha-fetoprotein: a clinicopathologic study of ten cases. Oncol
8. Pishgar F, Haj-Mirzaian A, Ebrahimi H, et al. Global, regional and Rep 1998;5:1425-1429. Available at:
national burden of testicular cancer, 1990-2016: results from the Global https://www.ncbi.nlm.nih.gov/pubmed/9769381.
Burden of Disease Study 2016. BJU Int 2019;124:386-394. Available at: 18. Kundu SD, Carver BS, Sheinfeld J. Retroperitoneal histologic findings
https://www.ncbi.nlm.nih.gov/pubmed/30953597. of patients with elevated serum alpha-fetoprotein and pure seminoma at
9. Ghazarian AA, McGlynn KA. Increasing Incidence of Testicular Germ orchiectomy. Urology 2011;78:844-847. Available at:
Cell Tumors among Racial/Ethnic Minorities in the United States. Cancer https://www.ncbi.nlm.nih.gov/pubmed/21782217.
Epidemiol Biomarkers Prev 2020;29:1237-1245. Available at: 19. Gilligan TD, Seidenfeld J, Basch EM, et al. American Society of
https://www.ncbi.nlm.nih.gov/pubmed/32385118. Clinical Oncology Clinical Practice Guideline on uses of serum tumor

Version 2.2024 © 2024 National Comprehensive Cancer Network© (NCCN©), All rights reserved. NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN.
MS-29
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NCCN Guidelines Version 2.2024

Testicular Cancer

markers in adult males with germ cell tumors. J Clin Oncol 2010;28:3388- Oncologist 2008;13:1149-1154. Available at:
3404. Available at: https://www.ncbi.nlm.nih.gov/pubmed/20530278. https://www.ncbi.nlm.nih.gov/pubmed/18984875.
20. Salem M, Gilligan T. Serum tumor markers and their utilization in the 28. Soares DG, Millot F, Lacroix I, Lotz JP. Heterophile Antibody
management of germ-cell tumors in adult males. Expert Rev Anticancer Interference led to Unneeded Chemotherapy in a Testicular Cancer
Ther 2011;11:1-4. Available at: Patient. Urol Case Rep 2016;9:1-3. Available at:
https://www.ncbi.nlm.nih.gov/pubmed/21166503. https://www.ncbi.nlm.nih.gov/pubmed/27617210.
21. Adra N, Abonour R, Althouse SK, et al. High-Dose Chemotherapy and 29. Beyer J, Collette L, Sauve N, et al. Survival and New Prognosticators
Autologous Peripheral-Blood Stem-Cell Transplantation for Relapsed in Metastatic Seminoma: Results From the IGCCCG-Update Consortium.
Metastatic Germ Cell Tumors: The Indiana University Experience. J Clin J Clin Oncol 2021;39:1553-1562. Available at:
Oncol 2017;35:1096-1102. Available at: https://www.ncbi.nlm.nih.gov/pubmed/33729863.
https://www.ncbi.nlm.nih.gov/pubmed/27870561.
30. Kim W, Rosen MA, Langer JE, et al. US MR imaging correlation in
22. Ferraro S, Trevisiol C, Gion M, Panteghini M. Human Chorionic pathologic conditions of the scrotum. Radiographics 2007;27:1239-1253.
Gonadotropin Assays for Testicular Tumors: Closing the Gap between Available at: https://www.ncbi.nlm.nih.gov/pubmed/17848688.
Clinical and Laboratory Practice. Clin Chem 2018;64:270-278. Available
31. Egan J, Cheaib JG, Biles MJ, et al. Testis-sparing Surgery: A Single
at: https://www.ncbi.nlm.nih.gov/pubmed/29021329.
Institution Experience. Urology 2021;147:192-198. Available at:
23. Lempiainen A, Hotakainen K, Blomqvist C, et al. Increased human https://www.ncbi.nlm.nih.gov/pubmed/33137349.
chorionic gonadotropin due to hypogonadism after treatment of a testicular
32. Nason GJ, Aditya I, Leao R, et al. Partial orchiectomy: The Princess
seminoma. Clin Chem 2007;53:1560-1561. Available at:
Margaret cancer centre experience. Urol Oncol 2020;38:605 e619-605
https://www.ncbi.nlm.nih.gov/pubmed/17644799.
e624. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32284257.
24. Morris MJ, Bosl GJ. Recognizing abnormal marker results that do not
33. Scandura G, Verrill C, Protheroe A, et al. Incidentally detected
reflect disease in patients with germ cell tumors. J Urol 2000;163:796-801.
testicular lesions <10 mm in diameter: can orchidectomy be avoided? BJU
Available at: https://www.ncbi.nlm.nih.gov/pubmed/10687980.
Int 2018;121:575-582. Available at:
25. Michalski W, Poniatowska G, Jońska-Gmyrek J, et al. hCG-secreting https://www.ncbi.nlm.nih.gov/pubmed/29032579.
malignancies — diagnostic pitfalls. Oncol Clin Pract 2019;15:331-335.
34. Jones RH, Vasey PA. Part I: testicular cancer--management of early
Available at:
disease. Lancet Oncol 2003;4:730-737. Available at:
https://journals.viamedica.pl/oncology_in_clinical_practice/article/view/658
https://www.ncbi.nlm.nih.gov/pubmed/14662429.
34.
35. Dieckmann KP, Anheuser P, Schmidt S, et al. Testicular prostheses in
26. Trojan A, Joller-Jemelka H, Stahel RA, et al. False-positive human
patients with testicular cancer - acceptance rate and patient satisfaction.
serum chorionic gonadotropin in a patient with a history of germ cell
BMC Urol 2015;15:16. Available at:
cancer. Oncology 2004;66:336-338. Available at:
https://www.ncbi.nlm.nih.gov/pubmed/25887552.
https://www.ncbi.nlm.nih.gov/pubmed/15218303.
36. Robinson R, Tait CD, Clarke NW, Ramani VA. Is it safe to insert a
27. Ballieux BE, Weijl NI, Gelderblom H, et al. False-positive serum
testicular prosthesis at the time of radical orchidectomy for testis cancer:
human chorionic gonadotropin (HCG) in a male patient with a malignant
an audit of 904 men undergoing radical orchidectomy. BJU Int
germ cell tumor of the testis: a case report and review of the literature.

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NCCN Guidelines Version 2.2024

Testicular Cancer

2016;117:249-252. Available at: 45. Yilmaz A, Cheng T, Zhang J, Trpkov K. Testicular hilum and vascular
https://www.ncbi.nlm.nih.gov/pubmed/25168859. invasion predict advanced clinical stage in nonseminomatous germ cell
tumors. Mod Pathol 2013;26:579-586. Available at:
37. Yossepowitch O, Aviv D, Wainchwaig L, Baniel J. Testicular
https://www.ncbi.nlm.nih.gov/pubmed/23238629.
prostheses for testis cancer survivors: patient perspectives and predictors
of long-term satisfaction. J Urol 2011;186:2249-2252. Available at: 46. Trevino KE, Esmaeili-Shandiz A, Saeed O, et al. Pathological risk
https://www.ncbi.nlm.nih.gov/pubmed/22014806. factors for higher clinical stage in testicular seminomas. Histopathology
2018;73:741-747. Available at:
38. Fankhauser CD, Roth L, Kranzbuhler B, et al. The Role of Frozen
https://www.ncbi.nlm.nih.gov/pubmed/29858564.
Section Examination During Inguinal Exploration in Men with Inconclusive
Testicular Tumors: A Systematic Review and Meta-analysis. Eur Urol 47. Tandstad T, Stahl O, Hakansson U, et al. One course of adjuvant BEP
Focus 2021;7:1400-1402. Available at: in clinical stage I nonseminoma mature and expanded results from the
https://www.ncbi.nlm.nih.gov/pubmed/32684510. SWENOTECA group. Ann Oncol 2014;25:2167-2172. Available at:
https://www.ncbi.nlm.nih.gov/pubmed/25114021.
39. Fossa SD, Chen J, Schonfeld SJ, et al. Risk of contralateral testicular
cancer: a population-based study of 29,515 U.S. men. J Natl Cancer Inst 48. Ernst DS, Brasher P, Venner PM, et al. Compliance and outcome of
2005;97:1056-1066. Available at: patients with stage 1 non-seminomatous germ cell tumors (NSGCT)
https://www.ncbi.nlm.nih.gov/pubmed/16030303. managed with surveillance programs in seven Canadian centres. Can J
Urol 2005;12:2575-2580. Available at:
40. Ragni G, Somigliana E, Restelli L, et al. Sperm banking and rate of
https://www.ncbi.nlm.nih.gov/pubmed/15877938.
assisted reproduction treatment: insights from a 15-year cryopreservation
program for male cancer patients. Cancer 2003;97:1624-1629. Available 49. Lago-Hernandez CA, Feldman H, O'Donnell E, et al. A refined risk
at: https://www.ncbi.nlm.nih.gov/pubmed/12655518. stratification scheme for clinical stage 1 NSGCT based on evaluation of
both embryonal predominance and lymphovascular invasion. Ann Oncol
41. Saito K, Suzuki K, Iwasaki A, et al. Sperm cryopreservation before
2015;26:1396-1401. Available at:
cancer chemotherapy helps in the emotional battle against cancer. Cancer
https://www.ncbi.nlm.nih.gov/pubmed/25888612.
2005;104:521-524. Available at:
https://www.ncbi.nlm.nih.gov/pubmed/15968690. 50. Kobayashi K, Saito T, Kitamura Y, et al. Oncological outcomes in
patients with stage I testicular seminoma and nonseminoma: pathological
42. Brydoy M, Fossa SD, Klepp O, et al. Paternity following treatment for
risk factors for relapse and feasibility of surveillance after orchiectomy.
testicular cancer. J Natl Cancer Inst 2005;97:1580-1588. Available at:
Diagn Pathol 2013;8:57. Available at:
https://www.ncbi.nlm.nih.gov/pubmed/16264178.
https://www.ncbi.nlm.nih.gov/pubmed/23566361.
43. Huyghe E, Matsuda T, Daudin M, et al. Fertility after testicular cancer
51. Soper MS, Hastings JR, Cosmatos HA, et al. Observation versus
treatments: results of a large multicenter study. Cancer 2004;100:732-737.
adjuvant radiation or chemotherapy in the management of stage I
Available at: https://www.ncbi.nlm.nih.gov/pubmed/14770428.
seminoma: clinical outcomes and prognostic factors for relapse in a large
44. Paner GP, Stadler WM, Hansel DE, et al. Updates in the Eighth US cohort. Am J Clin Oncol 2014;37:356-359. Available at:
Edition of the Tumor-Node-Metastasis Staging Classification for Urologic https://www.ncbi.nlm.nih.gov/pubmed/23275274.
Cancers. Eur Urol 2018;73:560-569. Available at:
52. Sturgeon JF, Moore MJ, Kakiashvili DM, et al. Non-risk-adapted
https://www.ncbi.nlm.nih.gov/pubmed/29325693.
surveillance in clinical stage I nonseminomatous germ cell tumors: the

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Testicular Cancer

Princess Margaret Hospital's experience. Eur Urol 2011;59:556-562. 61. Heidenreich A, Sesterhenn IA, Mostofi FK, Moul JW. Prognostic risk
Available at: https://www.ncbi.nlm.nih.gov/pubmed/21190791. factors that identify patients with clinical stage I nonseminomatous germ
cell tumors at low risk and high risk for metastasis. Cancer 1998;83:1002-
53. Leman ES, Gonzalgo ML. Prognostic features and markers for
1011. Available at: https://www.ncbi.nlm.nih.gov/pubmed/9731905.
testicular cancer management. Indian J Urol 2010;26:76-81. Available at:
https://www.ncbi.nlm.nih.gov/pubmed/20535291. 62. Alexandre J, Fizazi K, Mahe C, et al. Stage I non-seminomatous germ-
cell tumours of the testis: identification of a subgroup of patients with a
54. Gordetsky J, Sanfrancesco J, Epstein JI, et al. Do Nonseminomatous
very low risk of relapse. Eur J Cancer 2001;37:576-582. Available at:
Germ Cell Tumors of the Testis With Lymphovascular Invasion of the
https://www.ncbi.nlm.nih.gov/pubmed/11290432.
Spermatic Cord Merit Staging as pT3? Am J Surg Pathol 2017;41:1397-
1402. Available at: https://www.ncbi.nlm.nih.gov/pubmed/28719463. 63. Sweeney CJ, Hermans BP, Heilman DK, et al. Results and outcome of
retroperitoneal lymph node dissection for clinical stage I embryonal
55. Nazeer T, Ro JY, Kee KH, Ayala AG. Spermatic cord contamination in
carcinoma--predominant testis cancer. J Clin Oncol 2000;18:358-362.
testicular cancer. Mod Pathol 1996;9:762-766. Available at:
Available at: https://www.ncbi.nlm.nih.gov/pubmed/10637250.
https://www.ncbi.nlm.nih.gov/pubmed/8832559.
64. Albers P, Siener R, Kliesch S, et al. Risk factors for relapse in clinical
56. Blok JM, Pluim I, Daugaard G, et al. Lymphovascular invasion and
stage I nonseminomatous testicular germ cell tumors: results of the
presence of embryonal carcinoma as risk factors for occult metastatic
German Testicular Cancer Study Group Trial. J Clin Oncol 2003;21:1505-
disease in clinical stage I nonseminomatous germ cell tumour: a
1512. Available at: https://www.ncbi.nlm.nih.gov/pubmed/12697874.
systematic review and meta-analysis. BJU Int 2020;125:355-368.
Available at: https://www.ncbi.nlm.nih.gov/pubmed/31797520. 65. Sanfrancesco JM, Trevino KE, Xu H, et al. The Significance of
Spermatic Cord Involvement by Testicular Germ Cell Tumors: Should We
57. Divrik RT, Akdogan B, Ozen H, Zorlu F. Outcomes of surveillance
Be Staging Discontinuous Invasion From Involved Lymphovascular
protocol of clinical stage I nonseminomatous germ cell tumors-is shift to
Spaces Differently From Direct Extension? Am J Surg Pathol
risk adapted policy justified? J Urol 2006;176:1424-1429; discussion 1429-
2018;42:306-311. Available at:
1430. Available at: https://www.ncbi.nlm.nih.gov/pubmed/16952649.
https://www.ncbi.nlm.nih.gov/pubmed/29309304.
58. Gilbert DC, Al-Saadi R, Thway K, et al. Defining a New Prognostic
66. Moch H, Cubilla AL, Humphrey PA, et al. The 2016 WHO
Index for Stage I Nonseminomatous Germ Cell Tumors Using CXCL12
Classification of Tumours of the Urinary System and Male Genital Organs-
Expression and Proportion of Embryonal Carcinoma. Clin Cancer Res
Part A: Renal, Penile, and Testicular Tumours. Eur Urol 2016;70:93-105.
2016;22:1265-1273. Available at:
Available at: https://www.ncbi.nlm.nih.gov/pubmed/26935559.
https://www.ncbi.nlm.nih.gov/pubmed/26453693.
67. Williamson SR, Delahunt B, Magi-Galluzzi C, et al. The World Health
59. Vergouwe Y, Steyerberg EW, Eijkemans MJ, et al. Predictors of occult
Organization 2016 classification of testicular germ cell tumours: a review
metastasis in clinical stage I nonseminoma: a systematic review. J Clin
and update from the International Society of Urological Pathology Testis
Oncol 2003;21:4092-4099. Available at:
Consultation Panel. Histopathology 2017;70:335-346. Available at:
https://www.ncbi.nlm.nih.gov/pubmed/14559885.
https://www.ncbi.nlm.nih.gov/pubmed/27747907.
60. Daugaard G, Gundgaard MG, Mortensen MS, et al. Surveillance for
68. International Germ Cell Consensus Classification: a prognostic factor-
stage I nonseminoma testicular cancer: outcomes and long-term follow-up
based staging system for metastatic germ cell cancers. International Germ
in a population-based cohort. J Clin Oncol 2014;32:3817-3823. Available
Cell Cancer Collaborative Group. J Clin Oncol 1997;15:594-603. Available
at: https://www.ncbi.nlm.nih.gov/pubmed/25267754.
at: https://www.ncbi.nlm.nih.gov/pubmed/9053482.

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Testicular Cancer

69. Gillessen S, Sauve N, Collette L, et al. Predicting Outcomes in Men 77. Zengerling F, Kunath F, Jensen K, et al. Prognostic factors for tumor
With Metastatic Nonseminomatous Germ Cell Tumors (NSGCT): Results recurrence in patients with clinical stage I seminoma undergoing
From the IGCCCG Update Consortium. J Clin Oncol 2021;39:1563-1574. surveillance-A systematic review. Urol Oncol 2018;36:448-458. Available
Available at: https://www.ncbi.nlm.nih.gov/pubmed/33822655. at: https://www.ncbi.nlm.nih.gov/pubmed/28712790.
70. Mead GM, Fossa SD, Oliver RT, et al. Randomized trials in 2466 78. Aparicio J, Maroto P, Garcia Del Muro X, et al. Prognostic factors for
patients with stage I seminoma: patterns of relapse and follow-up. J Natl relapse in stage I seminoma: a new nomogram derived from three
Cancer Inst 2011;103:241-249. Available at: consecutive, risk-adapted studies from the Spanish Germ Cell Cancer
https://www.ncbi.nlm.nih.gov/pubmed/21212385. Group (SGCCG). Ann Oncol 2014;25:2173-2178. Available at:
https://www.ncbi.nlm.nih.gov/pubmed/25210015.
71. Tandstad T, Stahl O, Dahl O, et al. Treatment of stage I seminoma,
with one course of adjuvant carboplatin or surveillance, risk-adapted 79. Chung P, Daugaard G, Tyldesley S, et al. Evaluation of a prognostic
recommendations implementing patient autonomy: a report from the model for risk of relapse in stage I seminoma surveillance. Cancer Med
Swedish and Norwegian Testicular Cancer Group (SWENOTECA). Ann 2015;4:155-160. Available at:
Oncol 2016;27:1299-1304. Available at: https://www.ncbi.nlm.nih.gov/pubmed/25236854.
https://www.ncbi.nlm.nih.gov/pubmed/27052649.
80. Chung P, Warde P. Stage I seminoma: adjuvant treatment is effective
72. Aparicio J, Garcia del Muro X, Maroto P, et al. Multicenter study but is it necessary? J Natl Cancer Inst 2011;103:194-196. Available at:
evaluating a dual policy of postorchiectomy surveillance and selective https://www.ncbi.nlm.nih.gov/pubmed/21212383.
adjuvant single-agent carboplatin for patients with clinical stage I
81. Mortensen MS, Lauritsen J, Gundgaard MG, et al. A nationwide cohort
seminoma. Ann Oncol 2003;14:867-872. Available at:
study of stage I seminoma patients followed on a surveillance program.
https://www.ncbi.nlm.nih.gov/pubmed/12796024.
Eur Urol 2014;66:1172-1178. Available at:
73. Warde P, Specht L, Horwich A, et al. Prognostic factors for relapse in https://www.ncbi.nlm.nih.gov/pubmed/25064686.
stage I seminoma managed by surveillance: a pooled analysis. J Clin
82. Boormans JL, Mayor de Castro J, Marconi L, et al. Testicular Tumour
Oncol 2002;20:4448-4452. Available at:
Size and Rete Testis Invasion as Prognostic Factors for the Risk of
https://www.ncbi.nlm.nih.gov/pubmed/12431967.
Relapse of Clinical Stage I Seminoma Testis Patients Under Surveillance:
74. Chung P, Parker C, Panzarella T, et al. Surveillance in stage I a Systematic Review by the Testicular Cancer Guidelines Panel. Eur Urol
testicular seminoma - risk of late relapse. Can J Urol 2002;9:1637-1640. 2018;73:394-405. Available at:
Available at: https://www.ncbi.nlm.nih.gov/pubmed/12431325. https://www.ncbi.nlm.nih.gov/pubmed/29100813.
75. Groll RJ, Warde P, Jewett MA. A comprehensive systematic review of 83. Oliver RT, Mason MD, Mead GM, et al. Radiotherapy versus single-
testicular germ cell tumor surveillance. Crit Rev Oncol Hematol dose carboplatin in adjuvant treatment of stage I seminoma: a randomised
2007;64:182-197. Available at: trial. Lancet 2005;366:293-300. Available at:
https://www.ncbi.nlm.nih.gov/pubmed/17644403. https://www.ncbi.nlm.nih.gov/pubmed/16039331.
76. Escudero-Avila R, Rodriguez-Castano JD, Osman I, et al. Active 84. Oliver RT, Mead GM, Rustin GJ, et al. Randomized trial of carboplatin
surveillance as a successful management strategy for patients with clinical versus radiotherapy for stage I seminoma: mature results on relapse and
stage I germ cell testicular cancer. Clin Transl Oncol 2019;21:796-804. contralateral testis cancer rates in MRC TE19/EORTC 30982 study
Available at: https://www.ncbi.nlm.nih.gov/pubmed/30470992. (ISRCTN27163214). J Clin Oncol 2011;29:957-962. Available at:
https://www.ncbi.nlm.nih.gov/pubmed/21282539.

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NCCN Guidelines Version 2.2024

Testicular Cancer

85. van de Wetering RAW, Sleijfer S, Feldman DR, et al. Controversies in 93. Dieckmann KP, Dralle-Filiz I, Matthies C, et al. Testicular seminoma
the Management of Clinical Stage I Seminoma: Carboplatin a Decade in- clinical stage 1: treatment outcome on a routine care level. J Cancer Res
Time to Start Backing Out. J Clin Oncol 2018;36:837-840. Available at: Clin Oncol 2016;142:1599-1607. Available at:
https://www.ncbi.nlm.nih.gov/pubmed/29389229. https://www.ncbi.nlm.nih.gov/pubmed/27116691.
86. Huddart RA, Norman A, Shahidi M, et al. Cardiovascular disease as a 94. Travis LB, Curtis RE, Storm H, et al. Risk of second malignant
long-term complication of treatment for testicular cancer. J Clin Oncol neoplasms among long-term survivors of testicular cancer. J Natl Cancer
2003;21:1513-1523. Available at: Inst 1997;89:1429-1439. Available at:
https://www.ncbi.nlm.nih.gov/pubmed/12697875. https://www.ncbi.nlm.nih.gov/pubmed/9326912.
87. van den Belt-Dusebout AW, de Wit R, Gietema JA, et al. Treatment- 95. Travis LB, Fossa SD, Schonfeld SJ, et al. Second cancers among
specific risks of second malignancies and cardiovascular disease in 5-year 40,576 testicular cancer patients: focus on long-term survivors. J Natl
survivors of testicular cancer. J Clin Oncol 2007;25:4370-4378. Available Cancer Inst 2005;97:1354-1365. Available at:
at: https://www.ncbi.nlm.nih.gov/pubmed/17906202. https://www.ncbi.nlm.nih.gov/pubmed/16174857.
88. Groot HJ, Lubberts S, de Wit R, et al. Risk of Solid Cancer After 96. Beard CJ, Travis LB, Chen MH, et al. Outcomes in stage I testicular
Treatment of Testicular Germ Cell Cancer in the Platinum Era. J Clin seminoma: a population-based study of 9193 patients. Cancer
Oncol 2018;36:2504-2513. Available at: 2013;119:2771-2777. Available at:
https://www.ncbi.nlm.nih.gov/pubmed/29989856. https://www.ncbi.nlm.nih.gov/pubmed/23633409.
89. Aparicio J, Garcia Del Muro X, Maroto P, et al. Patterns of relapse and 97. Horwich A, Fossa SD, Huddart R, et al. Second cancer risk and
treatment outcome after active surveillance or adjuvant carboplatin for mortality in men treated with radiotherapy for stage I seminoma. Br J
stage I seminoma: a retrospective study of the Spanish Germ Cell Cancer Cancer 2014;110:256-263. Available at:
Group. Clin Transl Oncol 2021;23:58-64. Available at: https://www.ncbi.nlm.nih.gov/pubmed/24263066.
https://www.ncbi.nlm.nih.gov/pubmed/32462393.
98. McMahon CJ, Rofsky NM, Pedrosa I. Lymphatic metastases from
90. Aparicio J, Germa JR, Garcia del Muro X, et al. Risk-adapted pelvic tumors: anatomic classification, characterization, and staging.
management for patients with clinical stage I seminoma: the Second Radiology 2010;254:31-46. Available at:
Spanish Germ Cell Cancer Cooperative Group study. J Clin Oncol https://www.ncbi.nlm.nih.gov/pubmed/20032141.
2005;23:8717-8723. Available at:
99. Dinniwell R, Chan P, Czarnota G, et al. Pelvic lymph node topography
https://www.ncbi.nlm.nih.gov/pubmed/16260698.
for radiotherapy treatment planning from ferumoxtran-10 contrast-
91. Aparicio J, Maroto P, del Muro XG, et al. Risk-adapted treatment in enhanced magnetic resonance imaging. Int J Radiat Oncol Biol Phys
clinical stage I testicular seminoma: the third Spanish Germ Cell Cancer 2009;74:844-851. Available at:
Group study. J Clin Oncol 2011;29:4677-4681. Available at: https://www.ncbi.nlm.nih.gov/pubmed/19095369.
https://www.ncbi.nlm.nih.gov/pubmed/22042940.
100. Jones WG, Fossa SD, Mead GM, et al. Randomized trial of 30 versus
92. Koutsoukos K, Tzannis K, Christodoulou C, et al. Two cycles of 20 Gy in the adjuvant treatment of stage I Testicular Seminoma: a report
adjuvant carboplatin in stage I seminoma: 8-year experience by the on Medical Research Council Trial TE18, European Organisation for the
Hellenic Cooperative Oncology Group (HECOG). World J Urol Research and Treatment of Cancer Trial 30942 (ISRCTN18525328). J
2016;34:853-857. Available at: Clin Oncol 2005;23:1200-1208. Available at:
https://www.ncbi.nlm.nih.gov/pubmed/26410826. https://www.ncbi.nlm.nih.gov/pubmed/15718317.

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NCCN Guidelines Version 2.2024

Testicular Cancer

101. Fossa SD, Horwich A, Russell JM, et al. Optimal planning target 109. Vesprini D, Chung P, Tolan S, et al. Utility of serum tumor markers
volume for stage I testicular seminoma: A Medical Research Council during surveillance for stage I seminoma. Cancer 2012;118:5245-5250.
randomized trial. Medical Research Council Testicular Tumor Working Available at: https://www.ncbi.nlm.nih.gov/pubmed/22517478.
Group. J Clin Oncol 1999;17:1146. Available at:
110. Joffe JK, Cafferty FH, Murphy L, et al. Imaging Modality and
https://www.ncbi.nlm.nih.gov/pubmed/10561173.
Frequency in Surveillance of Stage I Seminoma Testicular Cancer:
102. Livsey JE, Taylor B, Mobarek N, et al. Patterns of relapse following Results From a Randomized, Phase III, Noninferiority Trial (TRISST). J
radiotherapy for stage I seminoma of the testis: implications for follow-up. Clin Oncol 2022;40:2468-2478. Available at:
Clin Oncol (R Coll Radiol) 2001;13:296-300. Available at: https://www.ncbi.nlm.nih.gov/pubmed/35298280.
https://www.ncbi.nlm.nih.gov/pubmed/11554630.
111. Tolan S, Vesprini D, Jewett MA, et al. No role for routine chest
103. Martin JM, Panzarella T, Zwahlen DR, et al. Evidence-based radiography in stage I seminoma surveillance. Eur Urol 2010;57:474-479.
guidelines for following stage 1 seminoma. Cancer 2007;109:2248-2256. Available at: https://www.ncbi.nlm.nih.gov/pubmed/19577354.
Available at: https://www.ncbi.nlm.nih.gov/pubmed/17437287.
112. De La Pena H, Sharma A, Glicksman C, et al. No longer any role for
104. van As NJ, Gilbert DC, Money-Kyrle J, et al. Evidence-based routine follow-up chest x-rays in men with stage I germ cell cancer. Eur J
pragmatic guidelines for the follow-up of testicular cancer: optimising the Cancer 2017;84:354-359. Available at:
detection of relapse. Br J Cancer 2008;98:1894-1902. Available at: https://www.ncbi.nlm.nih.gov/pubmed/28866371.
https://www.ncbi.nlm.nih.gov/pubmed/18542063.
113. Kollmannsberger C, Tandstad T, Bedard PL, et al. Patterns of
105. Garmezy B, Pagliaro LC. Choosing treatment for stage I seminoma: relapse in patients with clinical stage I testicular cancer managed with
who should get what? Oncology (Williston Park) 2009;23:753, 759. active surveillance. J Clin Oncol 2015;33:51-57. Available at:
Available at: https://www.ncbi.nlm.nih.gov/pubmed/19777759. https://www.ncbi.nlm.nih.gov/pubmed/25135991.
106. Choo R, Sandler H, Warde P, et al. Survey of radiation oncologists: 114. Classen J, Schmidberger H, Meisner C, et al. Radiotherapy for
practice patterns of the management of stage I seminoma of testis in stages IIA/B testicular seminoma: final report of a prospective multicenter
Canada and a selected group in the United States. Can J Urol clinical trial. J Clin Oncol 2003;21:1101-1106. Available at:
2002;9:1479-1485. Available at: https://www.ncbi.nlm.nih.gov/pubmed/12637477.
https://www.ncbi.nlm.nih.gov/pubmed/12010592.
115. Patterson H, Norman AR, Mitra SS, et al. Combination carboplatin
107. Mortensen MS, Bandak M, Kier MG, et al. Surveillance versus and radiotherapy in the management of stage II testicular seminoma:
adjuvant radiotherapy for patients with high-risk stage I seminoma. Cancer comparison with radiotherapy treatment alone. Radiother Oncol
2017;123:1212-1218. Available at: 2001;59:5-11. Available at:
https://www.ncbi.nlm.nih.gov/pubmed/27893934. https://www.ncbi.nlm.nih.gov/pubmed/11295200.
108. Glaser SM, Vargo JA, Balasubramani GK, Beriwal S. Surveillance 116. Detti B, Livi L, Scoccianti S, et al. Management of Stage II testicular
and Radiation Therapy for Stage I Seminoma--Have We Learned From seminoma over a period of 40 years. Urol Oncol 2009;27:534-538.
the Evidence? Int J Radiat Oncol Biol Phys 2016;94:75-84. Available at: Available at: https://www.ncbi.nlm.nih.gov/pubmed/18848787.
https://www.ncbi.nlm.nih.gov/pubmed/26700704.
117. Glaser SM, Vargo JA, Balasubramani GK, Beriwal S. Stage II
Testicular Seminoma: Patterns of Care and Survival by Treatment

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NCCN Guidelines Version 2.2024

Testicular Cancer

Strategy. Clin Oncol (R Coll Radiol) 2016;28:513-521. Available at: 125. de Wit R, Roberts JT, Wilkinson PM, et al. Equivalence of three or
https://www.ncbi.nlm.nih.gov/pubmed/27146264. four cycles of bleomycin, etoposide, and cisplatin chemotherapy and of a
3- or 5-day schedule in good-prognosis germ cell cancer: a randomized
118. Paly JJ, Lin CC, Gray PJ, et al. Management and outcomes of clinical
study of the European Organization for Research and Treatment of
stage IIA/B seminoma: Results from the National Cancer Data Base 1998-
Cancer Genitourinary Tract Cancer Cooperative Group and the Medical
2012. Pract Radiat Oncol 2016;6:e249-e258. Available at:
Research Council. J Clin Oncol 2001;19:1629-1640. Available at:
https://www.ncbi.nlm.nih.gov/pubmed/27345128.
https://www.ncbi.nlm.nih.gov/pubmed/11250991.
119. Gospodarwicz MK, Sturgeon JF, Jewett MA. Early stage and
126. Kondagunta GV, Bacik J, Bajorin D, et al. Etoposide and cisplatin
advanced seminoma: role of radiation therapy, surgery, and
chemotherapy for metastatic good-risk germ cell tumors. J Clin Oncol
chemotherapy. Semin Oncol 1998;25:160-173. Available at:
2005;23:9290-9294. Available at:
https://www.ncbi.nlm.nih.gov/pubmed/9562449.
https://www.ncbi.nlm.nih.gov/pubmed/16361627.
120. Tachibana I, Alabd A, Tong Y, et al. Primary Retroperitoneal Lymph
127. Cary C, Jacob JM, Albany C, et al. Long-Term Survival of Good-Risk
Node Dissection for Stage II Seminoma: Is Surgery the New Path
Germ Cell Tumor Patients After Postchemotherapy Retroperitoneal Lymph
Forward? J Clin Oncol 2023;41:3930-3938. Available at:
Node Dissection: A Comparison of BEP x 3 vs. EP x 4 and Treating
https://www.ncbi.nlm.nih.gov/pubmed/36730902.
Institution. Clin Genitourin Cancer 2018;16:e307-e313. Available at:
121. Daneshmand S, Cary C, Masterson T, et al. Surgery in Early https://www.ncbi.nlm.nih.gov/pubmed/29104087.
Metastatic Seminoma: A Phase II Trial of Retroperitoneal Lymph Node
128. Kawai K, Akaza H. Current status of chemotherapy in risk-adapted
Dissection for Testicular Seminoma With Limited Retroperitoneal
management for metastatic testicular germ cell cancer. Cancer Sci
Lymphadenopathy. J Clin Oncol 2023;41:3009-3018. Available at:
2010;101:22-28. Available at:
https://www.ncbi.nlm.nih.gov/pubmed/36913642.
https://www.ncbi.nlm.nih.gov/pubmed/19922501.
122. Heidenreich A, Paffenholz P, Hartmann F, et al. Retroperitoneal
129. Calabro F, Albers P, Bokemeyer C, et al. The contemporary role of
Lymph Node Dissection in Clinical Stage IIA/B Metastatic Seminoma:
chemotherapy for advanced testis cancer: a systematic review of the
Results of the COlogne Trial of Retroperitoneal Lymphadenectomy In
literature. Eur Urol 2012;61:1212-1221. Available at:
Metastatic Seminoma (COTRIMS). Eur Urol Oncol 2024;7:122-127.
https://www.ncbi.nlm.nih.gov/pubmed/22464311.
Available at: https://www.ncbi.nlm.nih.gov/pubmed/37438222.
130. Feldman DR, Bosl GJ, Sheinfeld J, Motzer RJ. Medical treatment of
123. Hiester A, Che Y, Lusch A, et al. Phase 2 Single-arm Trial of Primary
advanced testicular cancer. JAMA 2008;299:672-684. Available at:
Retroperitoneal Lymph Node Dissection in Patients with Seminomatous
https://www.ncbi.nlm.nih.gov/pubmed/18270356.
Testicular Germ Cell Tumors with Clinical Stage IIA/B (PRIMETEST). Eur
Urol 2023;84:25-31. Available at: 131. Fizazi K, Delva R, Caty A, et al. A risk-adapted study of cisplatin and
https://www.ncbi.nlm.nih.gov/pubmed/36372627. etoposide, with or without ifosfamide, in patients with metastatic
seminoma: results of the GETUG S99 multicenter prospective study. Eur
124. Papachristofilou A, Bedke J, Hayoz S, et al. Single-dose carboplatin
Urol 2014;65:381-386. Available at:
followed by involved-node radiotherapy for stage IIA and stage IIB
https://www.ncbi.nlm.nih.gov/pubmed/24094847.
seminoma (SAKK 01/10): a single-arm, multicentre, phase 2 trial. Lancet
Oncol 2022;23:1441-1450. Available at: 132. Yoshida T, Yonese J, Kitsukawa S, et al. [Treatment results of VIP
https://www.ncbi.nlm.nih.gov/pubmed/36228644. (etoposide, ifosfamide and cisplatin) chemotherapy as a first-line therapy
in metastatic germ cell tumors]. Nihon Hinyokika Gakkai Zasshi

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Testicular Cancer

2000;91:55-61. Available at: discussion 940. Available at:

https://www.ncbi.nlm.nih.gov/pubmed/10723177. https://www.ncbi.nlm.nih.gov/pubmed/18207171.
133. Ishioka J, Kageyama Y, Inoue M, et al. [Result of treatment for 141. Kondagunta GV, Bacik J, Donadio A, et al. Combination of paclitaxel,
advanced germ cell tumor in the last decade]. Nihon Hinyokika Gakkai ifosfamide, and cisplatin is an effective second-line therapy for patients
Zasshi 2010;101:539-546. Available at: with relapsed testicular germ cell tumors. J Clin Oncol 2005;23:6549-6555.
https://www.ncbi.nlm.nih.gov/pubmed/20387513. Available at: https://www.ncbi.nlm.nih.gov/pubmed/16170162.
134. Spermon JR, De Geus-Oei LF, Kiemeney LA, et al. The role of 142. Loehrer PJ, Sr., Lauer R, Roth BJ, et al. Salvage therapy in recurrent
(18)fluoro-2-deoxyglucose positron emission tomography in initial staging germ cell cancer: ifosfamide and cisplatin plus either vinblastine or
and re-staging after chemotherapy for testicular germ cell tumours. BJU etoposide. Ann Intern Med 1988;109:540-546. Available at:
Int 2002;89:549-556. Available at: https://www.ncbi.nlm.nih.gov/pubmed/2844110.
https://www.ncbi.nlm.nih.gov/pubmed/11942962.
143. Miller KD, Loehrer PJ, Gonin R, Einhorn LH. Salvage chemotherapy
135. De Santis M, Pont J. The role of positron emission tomography in with vinblastine, ifosfamide, and cisplatin in recurrent seminoma. J Clin
germ cell cancer. World J Urol 2004;22:41-46. Available at: Oncol 1997;15:1427-1431. Available at:
https://www.ncbi.nlm.nih.gov/pubmed/15024601. https://www.ncbi.nlm.nih.gov/pubmed/9193335.
136. De Santis M, Becherer A, Bokemeyer C, et al. 2-18fluoro-deoxy-D- 144. Kondagunta GV, Bacik J, Sheinfeld J, et al. Paclitaxel plus Ifosfamide
glucose positron emission tomography is a reliable predictor for viable followed by high-dose carboplatin plus etoposide in previously treated
tumor in postchemotherapy seminoma: an update of the prospective germ cell tumors. J Clin Oncol 2007;25:85-90. Available at:
multicentric SEMPET trial. J Clin Oncol 2004;22:1034-1039. Available at: https://www.ncbi.nlm.nih.gov/pubmed/17194908.
https://www.ncbi.nlm.nih.gov/pubmed/15020605.
145. Flechon A, Bompas E, Biron P, Droz JP. Management of post-
137. Becherer A, De Santis M, Karanikas G, et al. FDG PET is superior to chemotherapy residual masses in advanced seminoma. J Urol
CT in the prediction of viable tumour in post-chemotherapy seminoma 2002;168:1975-1979. Available at:
residuals. Eur J Radiol 2005;54:284-288. Available at: https://www.ncbi.nlm.nih.gov/pubmed/12394688.
https://www.ncbi.nlm.nih.gov/pubmed/15837411.
146. de Wit M, Brenner W, Hartmann M, et al. [18F]-FDG-PET in clinical
138. Treglia G, Sadeghi R, Annunziata S, et al. Diagnostic performance of stage I/II non-seminomatous germ cell tumours: results of the German
fluorine-18-fluorodeoxyglucose positron emission tomography in the multicentre trial. Ann Oncol 2008;19:1619-1623. Available at:
postchemotherapy management of patients with seminoma: systematic https://www.ncbi.nlm.nih.gov/pubmed/18453520.
review and meta-analysis. Biomed Res Int 2014;2014:852681. Available
147. Huddart RA, O'Doherty MJ, Padhani A, et al. 18fluorodeoxyglucose
at: https://www.ncbi.nlm.nih.gov/pubmed/24963486.
positron emission tomography in the prediction of relapse in patients with
139. Becherer A. PET in testicular cancer. Methods Mol Biol high-risk, clinical stage I nonseminomatous germ cell tumors: preliminary
2011;727:225-241. Available at: report of MRC Trial TE22--the NCRI Testis Tumour Clinical Study Group.
https://www.ncbi.nlm.nih.gov/pubmed/21331937. J Clin Oncol 2007;25:3090-3095. Available at:
https://www.ncbi.nlm.nih.gov/pubmed/17634488.
140. Hinz S, Schrader M, Kempkensteffen C, et al. The role of positron
emission tomography in the evaluation of residual masses after 148. Calaway AC, Einhorn LH, Masterson TA, et al. Adverse Surgical
chemotherapy for advanced stage seminoma. J Urol 2008;179:936-940; Outcomes Associated with Robotic Retroperitoneal Lymph Node

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Testicular Cancer

Dissection Among Patients with Testicular Cancer. Eur Urol 2019;76:607- 156. Stephenson AJ, Bosl GJ, Motzer RJ, et al. Retroperitoneal lymph
609. Available at: https://www.ncbi.nlm.nih.gov/pubmed/31174891. node dissection for nonseminomatous germ cell testicular cancer: impact
of patient selection factors on outcome. J Clin Oncol 2005;23:2781-2788.
149. Taylor J, Becher E, Wysock JS, et al. Primary Robot-assisted
Available at: https://www.ncbi.nlm.nih.gov/pubmed/15837993.
Retroperitoneal Lymph Node Dissection for Men with Nonseminomatous
Germ Cell Tumor: Experience from a Multi-institutional Cohort. Eur Urol 157. Bohlen D, Burkhard FC, Mills R, et al. Fertility and sexual function
Focus 2021;7:1403-1408. Available at: following orchiectomy and 2 cycles of chemotherapy for stage I high risk
https://www.ncbi.nlm.nih.gov/pubmed/32682794. nonseminomatous germ cell cancer. J Urol 2001;165:441-444. Available
at: https://www.ncbi.nlm.nih.gov/pubmed/11176393.
150. Abdul-Muhsin H, Rocco N, Navaratnam A, et al. Outcomes of post-
chemotherapy robot-assisted retroperitoneal lymph node dissection in 158. Chevreau C, Mazerolles C, Soulie M, et al. Long-term efficacy of two
testicular cancer: multi-institutional study. World J Urol 2021;39:3833- cycles of BEP regimen in high-risk stage I nonseminomatous testicular
3838. Available at: https://www.ncbi.nlm.nih.gov/pubmed/33959785. germ cell tumors with embryonal carcinoma and/or vascular invasion. Eur
Urol 2004;46:209-214; discussion 214-205. Available at:
151. Zuniga A, Kakiashvili D, Jewett MA. Surveillance in stage I
https://www.ncbi.nlm.nih.gov/pubmed/15245815.
nonseminomatous germ cell tumours of the testis. BJU Int 2009;104:1351-
1356. Available at: https://www.ncbi.nlm.nih.gov/pubmed/19840012. 159. Gietema JA, Meinardi MT, Sleijfer DT, et al. Routine chest X-rays
have no additional value in the detection of relapse during routine follow-
152. Oliver RT, Ong J, Shamash J, et al. Long-term follow-up of Anglian
up of patients treated with chemotherapy for disseminated non-
Germ Cell Cancer Group surveillance versus patients with Stage 1
seminomatous testicular cancer. Ann Oncol 2002;13:1616-1620. Available
nonseminoma treated with adjuvant chemotherapy. Urology 2004;63:556-
at: https://www.ncbi.nlm.nih.gov/pubmed/12377651.
561. Available at: https://www.ncbi.nlm.nih.gov/pubmed/15028457.
160. Bamias A, Aravantinos G, Kastriotis I, et al. Report of the long-term
153. Stephenson AJ, Bosl GJ, Bajorin DF, et al. Retroperitoneal lymph
efficacy of two cycles of adjuvant bleomycin/etoposide/cisplatin in patients
node dissection in patients with low stage testicular cancer with embryonal
with stage I testicular nonseminomatous germ-cell tumors (NSGCT): a risk
carcinoma predominance and/or lymphovascular invasion. J Urol
adapted protocol of the Hellenic Cooperative Oncology Group. Urol Oncol
2005;174:557-560; discussion 560. Available at:
2011;29:189-193. Available at:
https://www.ncbi.nlm.nih.gov/pubmed/16006891.
https://www.ncbi.nlm.nih.gov/pubmed/19362863.
154. Albers P, Siener R, Krege S, et al. Randomized phase III trial
161. Guney S, Guney N, Sonmez NC, Ergenekon E. Risk-adapted
comparing retroperitoneal lymph node dissection with one course of
management for patients with clinical stage I non-seminomatous germ cell
bleomycin and etoposide plus cisplatin chemotherapy in the adjuvant
tumour of the testis. Med Oncol 2009;26:136-142. Available at:
treatment of clinical stage I Nonseminomatous testicular germ cell tumors:
https://www.ncbi.nlm.nih.gov/pubmed/18821067.
AUO trial AH 01/94 by the German Testicular Cancer Study Group. J Clin
Oncol 2008;26:2966-2972. Available at: 162. Chovanec M, Hanna N, Cary KC, et al. Management of stage I
https://www.ncbi.nlm.nih.gov/pubmed/18458040. testicular germ cell tumours. Nat Rev Urol 2016;13:663-673. Available at:
https://www.ncbi.nlm.nih.gov/pubmed/27618772.
155. Tandstad T, Dahl O, Cohn-Cedermark G, et al. Risk-adapted
treatment in clinical stage I nonseminomatous germ cell testicular cancer: 163. Huddart RA, Reid AM. Adjuvant Therapy for Stage IB Germ Cell
the SWENOTECA management program. J Clin Oncol 2009;27:2122- Tumors: One versus Two Cycles of BEP. Adv Urol 2018;2018:8781698.
2128. Available at: https://www.ncbi.nlm.nih.gov/pubmed/19307506. Available at: https://www.ncbi.nlm.nih.gov/pubmed/29808086.

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NCCN Guidelines Version 2.2024

Testicular Cancer

164. Meinardi MT, Gietema JA, van der Graaf WT, et al. Cardiovascular 2019;31:653-658. Available at:
morbidity in long-term survivors of metastatic testicular cancer. J Clin https://www.ncbi.nlm.nih.gov/pubmed/31056287.
Oncol 2000;18:1725-1732. Available at:
173. Lv ZJ, Wu S, Dong P, et al. Clinical outcomes in patients with stage I
https://www.ncbi.nlm.nih.gov/pubmed/10764433.
non-seminomatous germ cell cancer. Asian J Androl 2013;15:558-563.
165. Chovanec M, Abu Zaid M, Hanna N, et al. Long-term toxicity of Available at: https://www.ncbi.nlm.nih.gov/pubmed/23685909.
cisplatin in germ-cell tumor survivors. Ann Oncol 2017;28:2670-2679.
174. Mezvrishvili Z, Managadze L. Three cycles of etoposide and cisplatin
Available at: https://www.ncbi.nlm.nih.gov/pubmed/29045502.
chemotherapy in clinical stage IS nonseminomatous testicular cancer. Int
166. Strumberg D, Brugge S, Korn MW, et al. Evaluation of long-term Urol Nephrol 2006;38:621-624. Available at:
toxicity in patients after cisplatin-based chemotherapy for non- https://www.ncbi.nlm.nih.gov/pubmed/17111082.
seminomatous testicular cancer. Ann Oncol 2002;13:229-236. Available
175. Stephenson AJ, Bosl GJ, Motzer RJ, et al. Nonrandomized
at: https://www.ncbi.nlm.nih.gov/pubmed/11885999.
comparison of primary chemotherapy and retroperitoneal lymph node
167. Fung C, Dinh P, Jr., Ardeshir-Rouhani-Fard S, et al. Toxicities dissection for clinical stage IIA and IIB nonseminomatous germ cell
Associated with Cisplatin-Based Chemotherapy and Radiotherapy in testicular cancer. J Clin Oncol 2007;25:5597-5602. Available at:
Long-Term Testicular Cancer Survivors. Adv Urol 2018;2018:8671832. https://www.ncbi.nlm.nih.gov/pubmed/18065732.
Available at: https://www.ncbi.nlm.nih.gov/pubmed/29670654.
176. Weissbach L, Bussar-Maatz R, Flechtner H, et al. RPLND or primary
168. Hartmann JT, Lipp HP. Toxicity of platinum compounds. Expert Opin chemotherapy in clinical stage IIA/B nonseminomatous germ cell tumors?
Pharmacother 2003;4:889-901. Available at: Results of a prospective multicenter trial including quality of life
https://www.ncbi.nlm.nih.gov/pubmed/12783586. assessment. Eur Urol 2000;37:582-594. Available at:
https://www.ncbi.nlm.nih.gov/pubmed/10765098.
169. Kerns SL, Fung C, Monahan PO, et al. Cumulative Burden of
Morbidity Among Testicular Cancer Survivors After Standard Cisplatin- 177. Rabbani F, Sheinfeld J, Farivar-Mohseni H, et al. Low-volume nodal
Based Chemotherapy: A Multi-Institutional Study. J Clin Oncol metastases detected at retroperitoneal lymphadenectomy for testicular
2018;36:1505-1512. Available at: cancer: pattern and prognostic factors for relapse. J Clin Oncol
https://www.ncbi.nlm.nih.gov/pubmed/29617189. 2001;19:2020-2025. Available at:
https://www.ncbi.nlm.nih.gov/pubmed/11283135.
170. Sprauten M, Darrah TH, Peterson DR, et al. Impact of long-term
serum platinum concentrations on neuro- and ototoxicity in Cisplatin- 178. Sheinfeld J, Motzer RJ, Rabbani F, et al. Incidence and clinical
treated survivors of testicular cancer. J Clin Oncol 2012;30:300-307. outcome of patients with teratoma in the retroperitoneum following primary
Available at: https://www.ncbi.nlm.nih.gov/pubmed/22184390. retroperitoneal lymph node dissection for clinical stages I and IIA
nonseminomatous germ cell tumors. J Urol 2003;170:1159-1162.
171. Haugnes HS, Stenklev NC, Brydoy M, et al. Hearing loss before and
Available at: https://www.ncbi.nlm.nih.gov/pubmed/14501715.
after cisplatin-based chemotherapy in testicular cancer survivors: a
longitudinal study. Acta Oncol 2018;57:1075-1083. Available at: 179. Stephenson AJ, Klein EA. Surgical management of low-stage
https://www.ncbi.nlm.nih.gov/pubmed/29384420. nonseminomatous germ cell testicular cancer. BJU Int 2009;104:1362-
1368. Available at: https://www.ncbi.nlm.nih.gov/pubmed/19840014.
172. Raphael MJ, Wei X, Karim S, et al. Neurotoxicity Among Survivors of
Testicular Cancer: A Population-based Study. Clin Oncol (R Coll Radiol) 180. Behnia M, Foster R, Einhorn LH, et al. Adjuvant bleomycin, etoposide
and cisplatin in pathological stage II non-seminomatous testicular cancer.

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the Indiana University experience. Eur J Cancer 2000;36:472-475. cell tumors: a randomized trial of the Genito-Urinary Group of the French
Available at: https://www.ncbi.nlm.nih.gov/pubmed/10717522. Federation of Cancer Centers (GETUG T93BP). Ann Oncol 2007;18:917-
924. Available at: https://www.ncbi.nlm.nih.gov/pubmed/17351252.
181. Kondagunta GV, Sheinfeld J, Mazumdar M, et al. Relapse-free and
overall survival in patients with pathologic stage II nonseminomatous germ 189. Jones RH, Vasey PA. Part II: testicular cancer--management of
cell cancer treated with etoposide and cisplatin adjuvant chemotherapy. J advanced disease. Lancet Oncol 2003;4:738-747. Available at:
Clin Oncol 2004;22:464-467. Available at: https://www.ncbi.nlm.nih.gov/pubmed/14662430.
https://www.ncbi.nlm.nih.gov/pubmed/14752068.
190. de Wit R, Stoter G, Sleijfer DT, et al. Four cycles of BEP vs four
182. McHugh DJ, Funt SA, Silber D, et al. Adjuvant Chemotherapy With cycles of VIP in patients with intermediate-prognosis metastatic testicular
Etoposide Plus Cisplatin for Patients With Pathologic Stage II non-seminoma: a randomized study of the EORTC Genitourinary Tract
Nonseminomatous Germ Cell Tumors. J Clin Oncol 2020;38:1332-1337. Cancer Cooperative Group. European Organization for Research and
Available at: https://www.ncbi.nlm.nih.gov/pubmed/32109195. Treatment of Cancer. Br J Cancer 1998;78:828-832. Available at:
https://www.ncbi.nlm.nih.gov/pubmed/9743309.
183. Carver BS, Shayegan B, Eggener S, et al. Incidence of metastatic
nonseminomatous germ cell tumor outside the boundaries of a modified 191. Culine S, Kramar A, Theodore C, et al. Randomized trial comparing
postchemotherapy retroperitoneal lymph node dissection. J Clin Oncol bleomycin/etoposide/cisplatin with alternating
2007;25:4365-4369. Available at: cisplatin/cyclophosphamide/doxorubicin and vinblastine/bleomycin
https://www.ncbi.nlm.nih.gov/pubmed/17906201. regimens of chemotherapy for patients with intermediate- and poor-risk
metastatic nonseminomatous germ cell tumors: Genito-Urinary Group of
184. Nonomura N, Nishimura K, Takaha N, et al. Nerve-sparing
the French Federation of Cancer Centers Trial T93MP. J Clin Oncol
retroperitoneal lymph node dissection for advanced testicular cancer after
2008;26:421-427. Available at:
chemotherapy. Int J Urol 2002;9:539-544. Available at:
https://www.ncbi.nlm.nih.gov/pubmed/18202419.
https://www.ncbi.nlm.nih.gov/pubmed/12445231.
192. Nichols CR, Catalano PJ, Crawford ED, et al. Randomized
185. King J, Althouse SK, Cary C, et al. Surveillance after complete
comparison of cisplatin and etoposide and either bleomycin or ifosfamide
response in patients with metastatic non-seminomatous germ-cell tumor
in treatment of advanced disseminated germ cell tumors: an Eastern
(NSGCT). Journal of Clinical Oncology 2021;39:5018-5018. Available at:
Cooperative Oncology Group, Southwest Oncology Group, and Cancer
https://ascopubs.org/doi/abs/10.1200/JCO.2021.39.15_suppl.5018.
and Leukemia Group B Study. J Clin Oncol 1998;16:1287-1293. Available
186. Horwich A, Norman A, Fisher C, et al. Primary chemotherapy for at: https://www.ncbi.nlm.nih.gov/pubmed/9552027.
stage II nonseminomatous germ cell tumors of the testis. J Urol
193. Funt SA, McHugh DJ, Tsai S, et al. Four Cycles of Etoposide plus
1994;151:72-77; discussion 77-78. Available at:
Cisplatin for Patients with Good-Risk Advanced Germ Cell Tumors.
https://www.ncbi.nlm.nih.gov/pubmed/8254836.
Oncologist 2021;26:483-491. Available at:
187. Donohue JP, Thornhill JA, Foster RS, et al. The role of https://www.ncbi.nlm.nih.gov/pubmed/33586274.
retroperitoneal lymphadenectomy in clinical stage B testis cancer: the
194. van Dijk MR, Steyerberg EW, Habbema JD. Survival of non-
Indiana University experience (1965 to 1989). J Urol 1995;153:85-89.
seminomatous germ cell cancer patients according to the IGCC
Available at: https://www.ncbi.nlm.nih.gov/pubmed/7966799.
classification: An update based on meta-analysis. Eur J Cancer
188. Culine S, Kerbrat P, Kramar A, et al. Refining the optimal 2006;42:820-826. Available at:
chemotherapy regimen for good-risk metastatic nonseminomatous germ- https://www.ncbi.nlm.nih.gov/pubmed/16574403.

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Testicular Cancer

195. Cafferty FH, White JD, Shamash J, et al. Long-term outcomes with tumors. Onkologie 2011;34:416-420. Available at:
intensive induction chemotherapy (carboplatin, bleomycin, vincristine and https://www.ncbi.nlm.nih.gov/pubmed/21934340.
cisplatin/bleomycin, etoposide and cisplatin) and standard bleomycin,
203. Kurobe M, Kawai K, Oikawa T, et al. Paclitaxel, ifosfamide, and
etoposide and cisplatin in poor prognosis germ cell tumours: A
cisplatin (TIP) as salvage and consolidation chemotherapy for advanced
randomised phase II trial (ISRCTN53643604). Eur J Cancer
germ cell tumor. J Cancer Res Clin Oncol 2015;141:127-133. Available at:
2020;127:139-149. Available at:
https://www.ncbi.nlm.nih.gov/pubmed/25062721.
https://www.ncbi.nlm.nih.gov/pubmed/32007714.
204. Einhorn LH, Williams SD, Chamness A, et al. High-dose
196. Kollmannsberger C, Daneshmand S, So A, et al. Management of
chemotherapy and stem-cell rescue for metastatic germ-cell tumors. N
disseminated nonseminomatous germ cell tumors with risk-based
Engl J Med 2007;357:340-348. Available at:
chemotherapy followed by response-guided postchemotherapy surgery. J
https://www.ncbi.nlm.nih.gov/pubmed/17652649.
Clin Oncol 2010;28:537-542. Available at:
https://www.ncbi.nlm.nih.gov/pubmed/20026807. 205. Feldman DR, Sheinfeld J, Bajorin DF, et al. TI-CE high-dose
chemotherapy for patients with previously treated germ cell tumors: results
197. Schmidt AH, Hoyer M, Jensen BFS, Agerbaek M. Limited post-
and prognostic factor analysis. J Clin Oncol 2010;28:1706-1713. Available
chemotherapy retroperitoneal resection of residual tumour in non-
at: https://www.ncbi.nlm.nih.gov/pubmed/20194867.
seminomatous testicular cancer: complications, outcome and quality of
life. Acta Oncol 2018;57:1084-1093. Available at: 206. Albers P, Ganz A, Hannig E, et al. Salvage surgery of
https://www.ncbi.nlm.nih.gov/pubmed/29537330. chemorefractory germ cell tumors with elevated tumor markers. J Urol
2000;164:381-384. Available at:
198. Heidenreich A, Haidl F, Paffenholz P, et al. Surgical management of
https://www.ncbi.nlm.nih.gov/pubmed/10893590.
complex residual masses following systemic chemotherapy for metastatic
testicular germ cell tumours. Ann Oncol 2017;28:362-367. Available at: 207. George DW, Foster RS, Hromas RA, et al. Update on late relapse of
https://www.ncbi.nlm.nih.gov/pubmed/27831507. germ cell tumor: a clinical and molecular analysis. J Clin Oncol
2003;21:113-122. Available at:
199. Daneshmand S, Albers P, Fossa SD, et al. Contemporary
http://www.ncbi.nlm.nih.gov/pubmed/12506179.
management of postchemotherapy testis cancer. Eur Urol 2012;62:867-
876. Available at: https://www.ncbi.nlm.nih.gov/pubmed/22938868. 208. Lipphardt ME, Albers P. Late relapse of testicular cancer. World J
Urol 2004;22:47-54. Available at:
200. Riggs SB, Burgess EF, Gaston KE, et al. Postchemotherapy surgery
https://www.ncbi.nlm.nih.gov/pubmed/15064970.
for germ cell tumors--what have we learned in 35 years? Oncologist
2014;19:498-506. Available at: 209. Oing C, Lorch A, Bokemeyer C. Ongoing Clinical Trials in Testicular
https://www.ncbi.nlm.nih.gov/pubmed/24718515. Cancer: The TIGER Trial. Oncol Res Treat 2016;39:553-556. Available at:
https://www.ncbi.nlm.nih.gov/pubmed/27614956.
201. Loehrer PJ, Sr., Gonin R, Nichols CR, et al. Vinblastine plus
ifosfamide plus cisplatin as initial salvage therapy in recurrent germ cell 210. McHugh DJ, Feldman DR. Conventional-Dose versus High-Dose
tumor. J Clin Oncol 1998;16:2500-2504. Available at: Chemotherapy for Relapsed Germ Cell Tumors. Adv Urol
https://www.ncbi.nlm.nih.gov/pubmed/9667270. 2018;2018:7272541. Available at:
https://www.ncbi.nlm.nih.gov/pubmed/29736168.
202. Park S, Lee S, Lee J, et al. Salvage chemotherapy with paclitaxel,
ifosfamide, and cisplatin (TIP) in relapsed or cisplatin-refractory germ cell 211. Lorch A, Bascoul-Mollevi C, Kramar A, et al. Conventional-dose
versus high-dose chemotherapy as first salvage treatment in male patients

Version 2.2024 © 2024 National Comprehensive Cancer Network© (NCCN©), All rights reserved. NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN.
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Testicular Cancer

with metastatic germ cell tumors: evidence from a large international 219. Kollmannsberger C, Beyer J, Liersch R, et al. Combination
database. J Clin Oncol 2011;29:2178-2184. Available at: chemotherapy with gemcitabine plus oxaliplatin in patients with intensively
https://www.ncbi.nlm.nih.gov/pubmed/21444870. pretreated or refractory germ cell cancer: a study of the German Testicular
Cancer Study Group. J Clin Oncol 2004;22:108-114. Available at:
212. Le DT, Durham JN, Smith KN, et al. Mismatch repair deficiency
https://www.ncbi.nlm.nih.gov/pubmed/14701772.
predicts response of solid tumors to PD-1 blockade. Science
2017;357:409-413. Available at: 220. Mulherin BP, Brames MJ, Einhorn LH. Long-term survival with
https://www.ncbi.nlm.nih.gov/pubmed/28596308. paclitaxel and gemcitabine for germ cell tumors after progression following
high-dose chemotherapy with tandem transplant. Am J Clin Oncol
213. Le DT, Uram JN, Wang H, et al. PD-1 Blockade in Tumors with
2015;38:373-376. Available at:
Mismatch-Repair Deficiency. N Engl J Med 2015;372:2509-2520.
https://www.ncbi.nlm.nih.gov/pubmed/26214082.
Available at: https://www.ncbi.nlm.nih.gov/pubmed/26028255.
221. Pectasides D, Pectasides M, Farmakis D, et al. Gemcitabine and
214. Lala M, Li TR, de Alwis DP, et al. A six-weekly dosing schedule for
oxaliplatin (GEMOX) in patients with cisplatin-refractory germ cell tumors:
pembrolizumab in patients with cancer based on evaluation using
a phase II study. Ann Oncol 2004;15:493-497. Available at:
modelling and simulation. Eur J Cancer 2020;131:68-75. Available at:
https://www.ncbi.nlm.nih.gov/pubmed/14998855.
https://www.ncbi.nlm.nih.gov/pubmed/32305010.
222. Seidel C, Oechsle K, Lorch A, et al. Efficacy and safety of
215. Marabelle A, Fakih M, Lopez J, et al. Association of tumour
gemcitabine, oxaliplatin, and paclitaxel in cisplatin-refractory germ cell
mutational burden with outcomes in patients with advanced solid tumours
cancer in routine care--Registry data from an outcomes research project of
treated with pembrolizumab: prospective biomarker analysis of the
the German Testicular Cancer Study Group. Urol Oncol 2016;34:167
multicohort, open-label, phase 2 KEYNOTE-158 study. Lancet Oncol
e121-168. Available at: https://www.ncbi.nlm.nih.gov/pubmed/26699830.
2020;21:1353-1365. Available at:
https://www.ncbi.nlm.nih.gov/pubmed/32919526. 223. Miller JC, Einhorn LH. Phase II study of daily oral etoposide in
refractory germ cell tumors. Semin Oncol 1990;17:36-39. Available at:
216. Bokemeyer C, Oechsle K, Honecker F, et al. Combination
https://www.ncbi.nlm.nih.gov/pubmed/2154858.
chemotherapy with gemcitabine, oxaliplatin, and paclitaxel in patients with
cisplatin-refractory or multiply relapsed germ-cell tumors: a study of the 224. U.S. Food and Drug Administration. FDA approves pembrolizumab
German Testicular Cancer Study Group. Ann Oncol 2008;19:448-453. for adults and children with TMB-H solid tumors. 2020. Available at:
Available at: https://www.ncbi.nlm.nih.gov/pubmed/18006893. https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-
pembrolizumab-adults-and-children-tmb-h-solid-tumors. Accessed
217. De Giorgi U, Rosti G, Aieta M, et al. Phase II study of oxaliplatin and
January 19, 2021.
gemcitabine salvage chemotherapy in patients with cisplatin-refractory
nonseminomatous germ cell tumor. Eur Urol 2006;50:1032-1038; 225. Prescribing information for pembrolizumab injection, for intravenous
discussion 1038-1039. Available at: use. 2024. Available at:
https://www.ncbi.nlm.nih.gov/pubmed/16757095. https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/125514s155l
bl.pdf. Accessed July 17, 2024.
218. Einhorn LH, Brames MJ, Juliar B, Williams SD. Phase II study of
paclitaxel plus gemcitabine salvage chemotherapy for germ cell tumors 226. Adra N, Einhorn LH, Althouse SK, et al. Phase II trial of
after progression following high-dose chemotherapy with tandem pembrolizumab in patients with platinum refractory germ-cell tumors: a
transplant. J Clin Oncol 2007;25:513-516. Available at: Hoosier Cancer Research Network Study GU14-206. Ann Oncol
https://www.ncbi.nlm.nih.gov/pubmed/17290059.

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Testicular Cancer

2018;29:209-214. Available at: 234. Carver BS, Shayegan B, Serio A, et al. Long-term clinical outcome
https://www.ncbi.nlm.nih.gov/pubmed/29045540. after postchemotherapy retroperitoneal lymph node dissection in men with
residual teratoma. J Clin Oncol 2007;25:1033-1037. Available at:
227. Feldman DR, Lorch A, Kramar A, et al. Brain Metastases in Patients
https://www.ncbi.nlm.nih.gov/pubmed/17261854.
With Germ Cell Tumors: Prognostic Factors and Treatment Options--An
Analysis From the Global Germ Cell Cancer Group. J Clin Oncol 235. Comiter CV, Kibel AS, Richie JP, et al. Prognostic features of
2016;34:345-351. Available at: teratomas with malignant transformation: a clinicopathological study of 21
https://www.ncbi.nlm.nih.gov/pubmed/26460295. cases. J Urol 1998;159:859-863. Available at:
https://www.ncbi.nlm.nih.gov/pubmed/9474169.
228. Schmoll HJ, Souchon R, Krege S, et al. European consensus on
diagnosis and treatment of germ cell cancer: a report of the European 236. Donadio AC, Motzer RJ, Bajorin DF, et al. Chemotherapy for
Germ Cell Cancer Consensus Group (EGCCCG). Ann Oncol teratoma with malignant transformation. J Clin Oncol 2003;21:4285-4291.
2004;15:1377-1399. Available at: Available at: https://www.ncbi.nlm.nih.gov/pubmed/14645417.
https://www.ncbi.nlm.nih.gov/pubmed/15319245.
237. Flood TA, Ulbright TM, Hirsch MS. "Embryonic-type Neuroectodermal
229. Beyer J, Albers P, Altena R, et al. Maintaining success, reducing Tumor" Should Replace "Primitive Neuroectodermal Tumor" of the Testis
treatment burden, focusing on survivorship: highlights from the third and Gynecologic Tract: A Rationale for New Nomenclature. Am J Surg
European consensus conference on diagnosis and treatment of germ-cell Pathol 2021;45:1299-1302. Available at:
cancer. Ann Oncol 2013;24:878-888. Available at: https://www.ncbi.nlm.nih.gov/pubmed/34232605.
https://www.ncbi.nlm.nih.gov/pubmed/23152360.
238. Al-Hader AA, Jain A, Al-Nasrallah N, Einhorn LH. Metastatic
230. Boyle HJ, Jouanneau E, Droz JP, Flechon A. Management of brain malignant transformation of teratoma to primitive neuroectodermal tumor
metastases from germ cell tumors: a single center experience. Oncology (PNET): results with PNET-based chemotherapy. Am J Clin Oncol
2013;85:21-26. Available at: 2015;38:364-366. Available at:
https://www.ncbi.nlm.nih.gov/pubmed/23816811. https://www.ncbi.nlm.nih.gov/pubmed/23799289.
231. Loriot Y, Pagliaro L, Flechon A, et al. Patterns of relapse in poor- 239. Wei C, Cary C, Masterson TA, et al. Adjuvant chemotherapy with
prognosis germ-cell tumours in the GETUG 13 trial: Implications for CAV/IE for malignant transformation of teratoma to primitive
assessment of brain metastases. Eur J Cancer 2017;87:140-146. neuroectodermal tumor (PNET): An institutional analysis from Indiana
Available at: https://www.ncbi.nlm.nih.gov/pubmed/29149760. University. Journal of Clinical Oncology 2021;39:5026-5026. Available at:
232. Kollmannsberger C, Nichols C, Bamberg M, et al. First-line high-dose 240. Punjani N, Winquist E, Power N. Do retroperitoneal extragonadal
chemotherapy +/- radiation therapy in patients with metastatic germ-cell germ cell tumours exist? Can Urol Assoc J 2015;9:381-384. Available at:
cancer and brain metastases. Ann Oncol 2000;11:553-559. Available at: https://www.ncbi.nlm.nih.gov/pubmed/26788225.
https://www.ncbi.nlm.nih.gov/pubmed/10907948.
233. Kalra M, Adra N, Hanna N, et al. High-dose chemotherapy plus
peripheral blood stem cell transplantation for patients with relapsed germ
cell tumors and active brain metastases. Cancer 2020;126:1202-1207.
Available at: https://www.ncbi.nlm.nih.gov/pubmed/31743434.

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