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Current Clinical Oncology
Maurie Markman, MD, Series Editor

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Rectal Cancer
International
Perspectives on
Multimodality
Management

Edited by

Brian G. Czito
Department of Radiation Oncology,
Duke University Medical Center, Durham, NC, USA

Christopher G. Willett
Department of Radiation Oncology,
Duke University Medical Center, Durham, NC, USA
Editors
Brian G. Czito Christopher G. Willett
Department of Radiation Oncology Department of Radiation Oncology
Duke University Medical Center Duke University Medical Center
Durham, NC Durham, NC
USA USA
[email protected] [email protected]

ISBN: 978-1-60761-566-8 e-ISBN: 978-1-60761-567-5

DOI: 10.1007/978-1-60761-567-5
Springer New York Dordrecht Heidelberg London

Library of Congress Control Number: 2010931685

© Springer Science+Business Media, LLC 2010

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Preface

Rectal Cancer: International Perspectives on Multimodality Management is a timely

analysis of the diagnosis, staging, pathology, and therapy of cancer of the rectum. This book
is intended as a useful resource for physicians, scientists, medical students, and allied health
personnel in the disciplines of radiology, gastroenterology, surgical oncology, medical oncol-
ogy, radiation oncology, and pathology. Renowned contributors from different medical dis-
ciplines have written their chapters in a thoughtful, provocative, and visual fashion.
Importantly, these chapters highlight the controversies in the diagnostic, staging, and thera-
peutic management of patients with rectal cancer while providing practical management
recommendations.
This book is divided into 18 chapters. Early chapters address the diagnosis and staging of
rectal cancer, highlighting the critical role of contemporary imaging in guiding treatment.
The remaining chapters focus on the multimodality management of rectal cancer from the
vantage points of surgery, pathology, chemotherapy, and radiation therapy. The major devel-
opments in surgery are reviewed first, including contemporary roles of local excision, total
mesorectal excision, lateral pelvic lymph node dissection, organ preservation approaches, as
well as the management of advanced, recurrent, and metastatic disease. Following is a chap-
ter describing the pathologic evaluation of rectal cancer specimens, with emphasis on proper
methodology and its clinical relevance to overall disease management. The final chapters
review the contemporary roles of chemotherapy (including with radiation therapy, adjuvant
and neoadjuvant settings without radiation therapy, as well as in metastatic disease) as well
as radiation therapy (including adjuvant and neoadjuvant approaches, short vs. long course
treatments, brachytherapy and contact therapy, nonoperative approaches utilizing definitive
chemoradiotherapy, and technical innovations).
We would like to thank the authors for their outstanding contributions which will aid us
in the understanding of this malignancy as well as the care of our patients. We would also
express thanks to the patients whose willingness has allowed continued therapeutic advances
to be made in this disease over the past three decades. We hope you enjoy reviewing this
work as much as we have.

Durham, NC Brian G. Czito

Christopher G. Willett

v
Contents

Preface............................................................................................................................. v
Contributors.................................................................................................................... ix
1 Clinical Staging: Endoscopic Techniques............................................................... 1
Hueylan Chern and W. Douglas Wong
2 Clinical Staging: CT and MRI................................................................................ 21
Gina Brown, Shwetal Dighe, and Fiona Taylor
3 Local Excision........................................................................................................ 37
Y. Nancy You and Heidi Nelson
4 Total Mesorectal Excision and Lateral Pelvic Lymph Node Dissection................. 53
Miranda Kusters, Yoshihiro Moriya, Harm J.T. Rutten,
and Cornelis J.H. van de Velde
5 Abdominoperineal Resection, Low Anterior Resection,
and Beyond............................................................................................................. 79
Kirk Ludwig, Lauren Kosinski, and Timothy Ridolfi
6 T4 and Recurrent Rectal Cancer............................................................................. 109
Jason Park and Jose Guillem
7 Surgical Management of Pulmonary Metastases.................................................... 123
Loretta Erhunmwunsee and Thomas A. D’Amico
8 Surgical and Ablative Management of Liver Metastases........................................ 131
Srinevas K. Reddy and Bryan M. Clary
9 Surgical Pathology.................................................................................................. 151
Nicholas P. West and Philip Quirke
10 Chemotherapy: Concurrent Delivery with Radiation Therapy............................... 165
Jean-François Bosset, Christophe Borg, Philippe Maingon,
Gilles Crehange, Stéphanie Servagi-Vernat, and Mathieu Bosset
11 Chemotherapy: Adjuvant and Neoadjuvant Approaches........................................ 175
Rachel Wong, David Cunningham, and Ian Chua
12 Chemotherapy: Metastatic Disease......................................................................... 189
Kathryn M. Field and John R. Zalcberg
13 Radiation Therapy: Adjuvant vs. Neoadjuvant Therapy......................................... 223
Rolf Sauer and Claus Rödel
14 Radiation Therapy: Short Versus Long Course...................................................... 235
Krzysztof Bujko and Magdalena Bujko

vii
viii Contents

15 Chemoradiation Therapy: Nonoperative Approaches............................................. 249

Angelita Habr-Gama, Rodrigo Perez, Igor Proscurshim,
and Joaquim Gama-Rodrigues
16 Contact X-Ray Therapy.......................................................................................... 267
Jean-Pierre Gérard, Robert Myerson, and A. Sun Myint
17 High-Dose-Rate Preoperative Endorectal Brachytherapy
for Patients with Rectal Cancer............................................................................... 277
Té Vuong, Slobodan Devic, and Ervin Podgorsak
18 Radiation Therapy: Technical Innovations............................................................. 289
Brian G. Czito and Christopher G. Willett
Index................................................................................................................. 307
Contributors

Christophe Borg, MD, PhD • Medical Oncology Department,

Besançon University Hospital, Besançon, France
Jean-François Bosset, MD • Radiotherapy-Oncology Department,
Besançon University Hospital, Besançon, France
Mathieu Bosset, MD • Radiotherapy-Oncology Department,
Besançon University Hospital, Besançon, France
Gina Brown, MD • Royal Marsden Hospital, Sutton, Surrey, UK
Krzysztof Bujko, MD • Department of Radiotherapy, Maria Sklodowska-Curie Memorial
Cancer Centre and Institute of Oncology, Warsaw, Poland
Magdalena Bujko, MD • Department of Radiotherapy, Maria Sklodowska-Curie Memorial
Cancer Centre and Institute of Oncology, Warsaw, Poland
Ian Chua, MD • Department of Medicine, Royal Marsden Hospital, Sutton, Surrey, UK
Hueylan Chern, MD • Department of Surgery, Memorial Sloan-Kettering Cancer Center,
New York, NY, USA
Bryan M. Clary, MD • Department of Surgery, Division of General Surgery,
Duke University Medical Center, Durham, NC, USA
Gilles Crehange, MD • Radiotherapy Department, Georges François Leclerc Center,
Dijon, France
David Cunningham, MD, FRCP • Department of Medicine, Royal Marsden Hospital,
Sutton, Surrey, UK
Brian G. Czito, MD • Department of Radiation Oncology, Duke University Medical
Center, Durham, NC, USA
Thomas A. D’Amico, MD • Department of Surgery, Division of General Surgery,
Duke University Medical Center, Durham, NC, USA
Slobodan Devic, PhD • Department of Medical Physics, McGill University,
Montreal, QC, Canada
Shwetal Dighe, MS (Mum), DNB, MRCS • Mayday University Hospital, Croydon, UK
Loretta Erhunmwunsee, MD • Department of Surgery, Division of General Surgery,
Duke University Medical Center, Durham, NC, USA
Kathryn M. Field, MBBS Hons, MD • Royal Melbourne Hospital, Victoria, Australia
Joaquim Gama-Rodrigues, MD, PhD • Department of Gastroenterology,
University of Sao Paulo, Sao Paulo, Brazil

ix
x Contributors

Jean-Pierre Gérard, MD • Department of Radiation Oncology, Centre Antoine

Lacassagne, Nice, France
Jose Guillem, MD, MPH • Department of Surgery, Memorial Sloan-Kettering Cancer
Center, New York, NY, USA
Angelita Habr-Gama, MD, PhD • Department of Gastroenterology, University
of Sao Paulo, Sao Paulo, Brazil
Lauren Kosinski, MD • Section of Colorectal Surgery, Department of Surgery,
Medical College of Wisconsin, Milwaukee, WI, USA
Miranda Kusters, MSc • Department of Surgery, Leiden University Medical Center,
Leiden, The Netherlands
Kirk Ludwig, MD • MCW/Froedtert Cancer Center and Department of Surgery,
Medical College of Wisconsin, Milwaukee, WI, USA
Philippe Maingon, MD, PhD • Radiotherapy Department, Georges François Leclerc
Center, Dijon, France
Yoshihiro Moriya, MD • Department of Colorectal Surgery, National Cancer Center
Hospital, Tokyo, Japan
Robert Myerson, MD, PhD • Department of Radiation Oncology, Washington University
of Medicine, St, Louis, MO, USA
A. Sun Myint, FRCP, FRCR • Clatterbridge Centre for Oncology, NHS Foundation Trust,
Wirral, UK
Heidi Nelson, MD • Division of Colon and Rectal Surgery, Mayo Clinic
College of Medicine, Rochester, MN, USA
Jason Park, MD, MEd • Department of Surgery, Memorial Sloan-Kettering
Cancer Center, New York, NY, USA
Rodrigo Perez, MD • Department of Gastroenterology, University of Sao Paulo,
Sao Paulo, Brazil
Ervin Podgorsak, PhD • Department of Medical Physics, McGill University, Montreal,
QC, Canada
Igor Proscurshim, MD • Department of Gastroenterology, University of Sao Paulo,
Sao Paulo, Brazil
Philip Quirke, PhD • Department of Pathology and Tumour Biology, Leeds Institute
of Molecular Medicine, University of Leeds, Leeds, UK
Srinevas K. Reddy, MD • Department of Surgery, Division of General Surgery,
Duke University Medical Center, Durham, NC, USA
Timothy Ridolfi, MD • Department of Surgery, Medical College of Wisconsin,
Milwaukee, WI, USA
Claus Rödel, MD • Department of Radiation Therapy and Oncology, University
of Frankfurt, Germany
Harm J.T. Rutten, PhD • Department of Surgery, Catherina Hospital, Eindhoven,
The Netherlands
Contributors xi

Rolf Sauer, MD • Department of Radiation Therapy, University of Erlangen, Germany

Stéphanie Servagi-Vernat, MD • Radiotherapy-Oncology Department,
Besançon University Hospital, Besançon, France
Fiona Taylor, MBBS, MRCS • Mayday University Hospital, Croydon, UK
Cornelis J.H. van de Velde, MD, PhD • Department of Surgery, Leiden University
Medical Center, Leiden, The Netherlands
Té Vuong, MD, FRCPC • Department of Radiation Oncology, McGill University,
Montreal, QC, Canada
Nicholas P. West, MB, ChB • Department of Pathology and Tumour Biology,
Leeds Institute of Molecular Medicine, University of Leeds, Leeds, UK
Christopher G. Willett, MD • Department of Radiation Oncology,
Duke University Medical Center, Durham, NC, USA
W. Douglas Wong, MD • Department of Surgery, Memorial Sloan-Kettering
Cancer Center, New York, NY, USA
Rachel Wong, MD • Department of Medicine, Royal Marsden Hospital,
Sutton, Surrey, UK
Y. Nancy You, MD, MHSc • Division of Colorectal Surgery, Department of Surgery,
Mayo Clinic, Rochester, MN, USA
John R. Zalcberg, MD, PhD • Division of Hematology and Medical Oncology and
Department of Medicine, Peter MacCallum Cancer Centre, University of Melbourne,
Melbourne, Australia
 1 Clinical Staging: Endoscopic
Techniques

Hueylan Chern and W. Douglas Wong

Introduction
The treatment of rectal cancer has advanced tremendously in the last decade, leading to
a decrease in local recurrence and an increase in sphincter-sparing rates. The importance of
preoperative staging in improving rectal cancer treatment cannot be overemphasized.
Accurate preoperative staging guides important management decisions, such as identifica-
tion of patients who will benefit from neoadjuvant therapy as well as those amenable to local
excision or sphincter-sparing surgery rather than abdominoperineal resection.
In randomized controlled trials, preoperative chemoradiation therapy for T3, T4, or N1
rectal cancers has been shown to result in lower toxicity and improved local control com-
pared with postoperative chemoradiotherapy (2). Local excision may be considered for some
T1 rectal cancers. However, local excision for T2 or more advanced lesions (including those
with positive. lymph nodes) is not generally recommended (3). Thus, it is of utmost impor-
tance that initial staging of rectal cancer be accurate and complete, in order to determine
individual T stage as well as nodal status.
Contemporary modalities used for preoperative staging of rectal cancer include digital
rectal exam (DRE), computed tomography (CT), magnetic resonance imaging (MRI), and
endorectal ultrasound (ERUS). The ideal staging modality should be relatively easy to per-
form, accurate, and cost-effective. This chapter focuses on ERUS, which is the authors’
initial staging method of choice.

For “Rectal Cancer: International Perspectives on Multimodality Management”, Brian G.

Czito, MD and Christopher G. Willett, MD, editors (Humana Press)

From: Current Clinical Oncology: Rectal Cancer,

Edited by: B.G. Czito and C.G. Willett, DOI: 10.1007/978-1-60761-567-5_1,
© Springer Science+Business Media, LLC 2010

1
2 H. Chern and W.D. Wong

Staging of Rectal Cancer

Many classification systems have been used for the staging of rectal cancer. In the
United States, the standard and most commonly used system is the tumor, node, metastasis
(TNM) staging system (4) (Table 1). Addition of the prefix “u” to a TNM classification
indicates that staging has been performed by ultrasound (5). At Memorial Sloan Kettering
Cancer Center (MSKCC), a modified ultrasound staging system has been proposed to
assist in clinical decision-making (Table 2). In this modified, treatment-oriented ultra-

Table 1
TNM staging system for rectal cancer

Primary tumor (T)

Tis Carcinoma in situ
T1 Tumor invades the submucosa
T2 Tumor invades the muscularis propria
T3 Tumor invades the perirectal fat
T4 Tumor directly invades adjacent organs and structures,
and/or perforates visceral peritoneum
Regional lymph nodes (N)
Nx Tumor cannot be assessed
N0 No regional metastases
N1 Metastases in one to three nodes
N2 Metastases in four or more regional nodes
Distant metastases (M)
Mx Distant metastases cannot be assessed
M0 No distant metastases
M1 Distant metastases
Staging
Stage 0 Tis N0 M0
Stage I T1-2 N0 M0
Stage IIA T3 N0 M0
Stage IIB T4 N0 M0
Stage IIIA T1-2 N1 M0
Stage IIIB T3-4 N1 M0
Stage IIIC Any T N2 M0
Stage IV Any T Any N M1

Table 2
MSKCC modified ERUS staging system

Stage Description
uTw uT0/T1 Amenable to local excision
uTy uT2/superficial uT3 Recommend radical surgery, may require neoadjuvant
therapy, pathologic features and nodal status helpful
in determining need for neoadjuvant therapy
uTz Deep uT3/any uT4 Recommend neoadjuvant therapy followed by radical resection
uN1 Probable or definite Recommend neoadjuvant therapy
uN1 Equivocal Base treatment on tumor stage and pathologic features
Chapter 1 / Clinical Staging: Endoscopic Techniques 3

sound staging system, uT0/T1 lesions are classified as potentially amenable to local exci-
sion and uT2/superficial uT3N0 tumors as potentially suitable for radical resection without
neoadjuvant therapy. Based on extramural depth of the tumor, uT3 lesions are further clas-
sified as superficial or deep; deep uT3/uT4 tumors should receive neoadjuvant therapy
prior to radical resection.

Staging Accuracy of Digital Rectal Exam (DRE)

The staging accuracy of DRE is not optimal and limited only to cancers that are palpable
on clinical exam. Starck et al. reported that about half of the patients in their study could be
evaluated with digital rectal exam (6). The accuracy of this modality in patients suitable for
evaluation by DRE is 68%. Others have reported varying DRE staging accuracies, ranging
from 57.9 to 82.8% (5). While DRE by itself is not a good staging modality, it does provide
the clinician with valuable information: distance of tumor from the anorectal sphincter com-
plex and tumor location, morphology, and mobility. It also allows the clinician to appreciate
the tumor and its relationship to surrounding anatomic structures, such as the vagina or the
prostate. In female patients, combining DRE with a vaginal examination enables the assess-
ment of the rectovaginal septum and its possible involvement by the tumor. An accurate
evaluation of anorectal sphincter involvement and the distance of tumor from the anorectal
sphincter complex are especially important when assessing the possibility of a sphincter-
saving procedure. Therefore, DRE remains an important step in the initial evaluation of
rectal cancer.

Staging Accuracy of CT, MRI, ERUS

Other staging modalities include CT, ERUS, and MRI. Each has its own advantages and
limitations. A meta-analysis by Kwok et al. best summarizes the comparative accuracy of
these imaging tools (1). The reported accuracy for T-staging is 84, 80, 74, and 81% for
ERUS, CT, MRI, and MRI with endorectal coil, respectively. The possibility of overstaging
is 11, 13, 13, and 12% for ERUS, CT, MRI, and MRI with endorectal coil, respectively; the
possibility of understaging is 5, 7, 13, and 6% for ERUS, CT, MRI, and MRI with endorectal
coil, respectively. In summary, ERUS appears to demonstrate the greatest reported accuracy
for assessing T-stage, at approximately 84%.
The accuracy of staging nodal status is 74, 66, 74, and 82% for ERUS, CT, MRI, and MRI
with endorectal coil, respectively, (1) indicating that MRI with endorectal coil may be the
most accurate in predicting nodal status. However, this modality has some limitations, which
will be discussed below.

Staging with CT
CT is a useful staging tool given its ability to evaluate primary lesions in the pelvis as
well as distant tumor spread. However, one major limitation of CT is its inability to differ-
entiate the individual layers of the rectal wall to accurately assess T-stage. Kim et al. reported
that CT has a T-staging accuracy of 82% in the setting of locally advanced T3 and T4 rectal
cancers; however, the accuracy drops to 15% for T2 rectal cancers (7). Therefore, while CT
accurately assesses the tumor penetrance of the rectal wall, it cannot be used with accuracy
to assign T-stage. Staging rectal cancers with CT alone is clearly inadequate, especially in
the setting of early tumors.
4 H. Chern and W.D. Wong

Staging with MRI

As advances were made in MRI technology, the accuracy of staging rectal cancers with
MRI improved significantly as well. While the initial reports on rectal cancer staging using
body coil MRI reported accuracy as low as 59%, accuracy as high as 86% has been reported
for MRI with phased-array coils (8, 9). The addition of endorectal coils to MRI allows
visualization of the individual rectal wall layers, similar to what is visualized on ERUS.
Studies have shown comparative staging accuracy between ERUS and MRI with endorectal
coils (10). However, MRI with endorectal coils has its drawbacks such as patient discomfort,
limited field of view when it is used as a solo modality, and significantly higher cost.
Therefore, it is unavailable at most centers.
Even though phased-array MRI is limited in evaluating the T-stage of an early rectal
cancer, it is very accurate in determining the likelihood of an involved circumferential resec-
tion margin, which is a powerful predictor of local recurrence (11). In addition, phased-array
MRI has demonstrated accuracy in evaluating advanced and recurrent tumors that invade
other pelvic structures (8). Hence, MRI remains an important tool for assisting surgeons in
the treatment of advanced and recurrent rectal cancer.

Staging with ERUS

One of the great advantages of ERUS is that it enables the operator to distinguish the
individual layers of the rectal wall. For this reason, it is considered the most accurate imag-
ing tool for the staging of early rectal cancers or benign adenomas. This helps the surgeon
determine which patients are suitable candidates for local excision and which patients should
be treated with neoadjuvant chemoradiation followed by more extensive resection. ERUS is
an especially useful and attractive method of initial evaluation for patients and clinicians
alike. Requiring minimal preparation by the patient, ERUS can be performed without
sedation during an office visit. The exam is generally well tolerated, and the results are
immediately available for use in discussing treatment options.
A limitation of ERUS is its suboptimal evaluation of more proximal, obstructing, or
stenotic lesions. It also provides a limited field of view, depending on the acoustic penetrance
of the ultrasound waves. Although another drawback of ERUS is that it is operator-dependent,
in experienced hands it is extremely accurate. Orrom et al. reported that with increasing
operator experience and standardization in interpreting ERUS, its staging accuracy increased
from 59.3 to 95% (12).

ERUS Technique
During a patient’s initial visit to our outpatient clinic, an evaluation form highlighting
many important elements necessary to a complete staging of rectal cancer (Table 3) is
routinely filled in.
The authors use a dedicated room in the clinic for ERUS. Two different types of ultrasound
probes are used: the Brüel & Kjær 1850 and the Brüel & Kjær 2052. Both can be utilized for
performing endoanal ultrasound as well as ERUS. The primary difference between the probes
is in the setup of the transducer. While the operator must physically move the 1850 probe
as the transducer moves along the entire length of the tumor, the 2052 probe remains still,
while the transducer rotates through the length of the probe itself.
Prior to ERUS, a balloon is fitted over the probe. When using the 1850 probe, the balloon
is usually inflated with 30–40 cc of water. When using the 2052 probe, a balloon is fitted
Chapter 1 / Clinical Staging: Endoscopic Techniques 5

Table 3
MSKCC outpatient clinic evaluation form

Educational form highlighting important elements of clinical staging of rectal cancer

over the entire probe and inflated with approximately 100 cc of fluid; this probe can also be
used without a balloon by inserting 100 cc of fluid directly into the rectum. The volume of
water depends on the size of the lesion, the diameter of the lumen, and the patient’s level of
comfort. To minimize the possible creation of artifact, it is important to avoid introducing air
into the balloon. Endoanal ultrasound can also be performed with the 1850 probe by fitting