Case Study: Low Risk Prostate Cancer
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This case study discusses treatment options for a 45-year-old man with low risk prostate cancer based on an elevated PSA. Screening is recommended due to his family history of prostate cancer in his father. Further testing reveals a small, low grade tumor. He is a candidate for active surveillance, brachytherapy, or radical prostatectomy. Active surveillance is preferred given his age and low risk profile to avoid overtreatment. Brachytherapy is also an option and has advantages over external beam radiation in reducing dose to surrounding organs. Close monitoring is needed as most low risk prostate cancer patients will not require immediate treatment.
![Can we recommend brachytherapy
monotherapy for this patient?
• Brachytherapy monotherapy can be considered in low-risk and low-volume
intermediate-risk prostate cancer.
• Contraindications [According to American Brachytherapy Society (ABS)]
• Absolute:
• High operative risk
• No rectum
• Limited life expectancy (<10 years)
• Distant metastasis
• Ataxia telangiectasia
• Relative:
• High IPSS (> 15–18)
• Prior pelvic RT
• Prior TURP
• large median lobe
• Gland volume >60 cc
• Inflammatory bowel disease](https://image.slidesharecdn.com/casestudyprostatekish-201103132148/85/Case-Study-Low-Risk-Prostate-Cancer-19-320.jpg)
Case Study: Low Risk Prostate Cancer
- 1. Case Study: Low Risk Prostate Cancer Ali Bagheri M.D Assistant Professor in Radiation Oncology Director of Brachytherapy Services at Ahvaz Golestan Hospital Ahvaz Jundishapur University of Medical Sciences
- 2. Do you recommend prostate cancer screening for this gentleman? • 45 year old • No complaints • Personal history → Normal • Family history → Prostate cancer in his father (at age of 60Y) • Medications History → Negative • Physical Examination → Normal
- 3. American Cancer Society (ACS) Guideline ≥50 years at average risk expected to live ≥10 years ≥45 years at high risk (African Americans, 1st-degree relatives diagnosed prior to 65 years) ≥40 years at very high risk (>1 1st-degree relative diagnosed prior to 65 years)
- 4. Is there evidence of a mortality benefit with prostate cancer screening? European Randomized study of Screening for Prostate Cancer (ERSPC) • Randomized 162,387 patients. • Follow-up = 13 years • Statistically significant 21% decreased risk of prostate cancer mortality with PSA screening detected. • The number needed to screen to prevent 1 death in this study was 781. U.S. Prostate, Lung, Colorectal, and Ovarian Cancer screening trial (PLCO) • Randomized 76,685 patients. • Annual PSA × 6 years + annual DRE × 4 years • Usual care in which opportunistic screening with PSA or DRE was allowed. • Follow-up = 13 years • Prostate cancer incidence was higher with PSA testing (108 vs. 97 cases/10,000 person- years). • The incidence of death was similar between the groups (3.7 vs. 3.4 cases/10,000 person- years) • Control group participants reported higher rates of PSA screening (∼90%) than those in the intervention group making it difficult to draw conclusions from this trial.
- 5. PSA = 3ng/mL & DRE → Normal • Is this serum PSA normal for this patient? • 40–49 years: 1.5–2.5 ng/mL • 50–59 years: 2.5–4 ng/mL • 60–69 years: 4–5.5 ng/mL • 70–79 years: 5.5–7 ng/mL • Would you recommend any other lab tests? • Repeat PSA • PSA Density (PSAD) = 0.12 ng/mL/cc (PSAD=PSA/Prostate volume) • A PSAD of ≥0.15 ng/mL/cc identifies men with a higher risk of detecting prostate cancer on a screening Bx. • Percent-free PSA = 6% (Free PSA/Total PSA) • A ratio of <7% is highly suspicious for prostate cancer.
- 6. Next Step? Multiparametric Pelvic MRI • Right base peripheral zone lesion (14 × 9mm) → PI-RADS 4 • No extracapsular extension (ECE) • No seminal vesicle invasion (SVI) • No pelvic lymphadenopathy (LAP)
- 7. TRUS-guided biopsy • 1/12 cores (right base) was positive for Adenocarcinoma. • Gleason Score (GS)=3+3 • 40% of the core was cancerous.
- 8. Clinical Stage? • cT1: Clinically inapparent tumor not palpable • cT1a: Incidental histologic finding in ≤5% of tumor resected • cT1b: Incidental histologic finding in >5% of tissue resected • cT1c: Tumor identified by needle Bx but not palpable • cT2: Palpable organ-confined disease • cT2a: Tumor involves one-half of 1 side or less • cT2b: Tumor involves more than one-half of 1 side but not both sides • cT2c: Tumor involve both sides • cT3: Extraprostatic tumor that is not fixed or does not invade adjacent structures • cT3a: ECE • cT3b: Seminal vesicle invasion • cT4: Adjacent organ involvement (bladder, external sphincter, rectum, pelvic wall, or levator muscles) • N1: regional lymph node metastasis • M1: Distant metastasis • M1a: Nonregional LNs • M1b: Bone(s) • M1c: Other sites c
- 9. Risk Stratification? • Very low: T1c, GS≤6, PSA<10ng/mL, <3 Bx cores +, ≤50% cancer per core, PSA density <0.15 ng/mL/g • Low: T1–T2a, GS≤6, PSA<10ng/mL • Intermediate: T2b–T2c or GS 7 or PSA 10–20ng/mL • High: T3a or GS 8–10 or PSA > 20ng/mL • Very high: T3b–T4 or primary Gleason pattern = 5 or >4 cores with GS 8-10 c
- 10. Would you recommend bone scan for this patient? c
- 11. Treatment Options? Active surveillance External beam radiation therapy (EBRT) or Brachytherapy Radical prostatectomy (RP)
- 12. Life Expectancy • Estimates of life expectancy have emerged as a key determinant of primary treatment, particularly when considering active surveillance or observation. • Life expectancy can be estimated using the WHO’s Life Tables by Country, and adjusted for individual patients by adding or subtracting 50% based on whether one believes the patient is in the healthiest quartile or the unhealthiest quartile, respectively. • As an example, if Life Expectancy for a 65-year-old man is 17.7 years. If judged to be in the upper quartile of health, a life expectancy of 26.5 years is assigned. If judged to be in the lower quartile of health, a life expectancy of 8.8 years is assigned.
- 14. Active Surveillance (preferred) • Active surveillance is the postponement of immediate therapy, with active monitoring and definitive treatment given if disease progresses. • Is in contrast to Observation that indicates monitoring for progression and offering palliative therapy as needed. • Protocol • PSA no more often than every 6 months unless clinically indicated. • DRE no more often than every 12 months unless clinically indicated. • Repeat prostate biopsy no more often than every 12 months unless clinically indicated. • Repeat mpMRI no more often than every 12 months unless clinically indicated.
- 15. ProtecT Trial • Randomized 1,643 men with localized prostate cancer (GS 6–10; T1c– T2) diagnosed by PSA testing to active monitoring, surgery, or radiotherapy + short-course ADT. • At a median of 10 tears of follow up there was no difference in prostate cancer–specific deaths or OS. • Metastatic disease was more common in the active monitoring group (6.3 events per 1,000 person-years) than in the surgery (2.4 per 1,000 person- years) or radiotherapy (3.0 per 1,000 years) groups (p = 0.004). • 27 men require surgery and 33 men require radiotherapy to prevent 1 patient from having metastatic disease.
- 16. One year after diagnosis • PSA = 5 ng/mL • PSA Velocity (PSAV) = 2 ng/ml/year (Is a measure of the rate of change of the total PSA annually) • PSAD = 0.2 ng/mL/cc (↑) • DRE → Positive • mpMRI • Right base peripheral zone lesion (19 × 10mm) (size↑) • No ECE • No SVI • No pelvic LAP • TRUS guided biopsy • 1/12 cores (right base) was positive for Adenocarcinoma. • GS=6 • 60% of the core was cancerous. A PSA velocity ≥2 ng/mL/y is associated with a higher risk of finding Gleason ≥7 prostate cancer on prostatectomy.
- 17. Active Surveillance • In a prospective cohort study at the Johns Hopkins Hospital of low- risk men undergoing active surveillance, the 10 and 15 year rates of curative intervention were 50% and 57%, respectively, with a 15-yr prostate-cancer mortality of 0.4%. A majority of men with low-risk prostate cancer would not have any adverse clinical consequences if left untreated. Active surveillance delays definitive treatment for the majority while reserving curative for those with disease progression.
- 18. Surgery vs. RT? (What ProtecT trial tell us?) • No differences in death due to prostate cancer with RP vs. EBRT + ADT. • Patient-reported Quality of Life (QOL) data showed: • Increased urinary pad use in the RP vs. RT groups at 6 months (46% vs. 5%) and 6 years (17% vs. 4%). • Bowel function was similar between groups except an increase in bloody stools in the radiotherapy group. • 17% and 27% of men could obtain erections adequate for intercourse at 6 years in the RP and RT groups, respectively, compared to 67% at baseline.
- 19. Can we recommend brachytherapy monotherapy for this patient? • Brachytherapy monotherapy can be considered in low-risk and low-volume intermediate-risk prostate cancer. • Contraindications [According to American Brachytherapy Society (ABS)] • Absolute: • High operative risk • No rectum • Limited life expectancy (<10 years) • Distant metastasis • Ataxia telangiectasia • Relative: • High IPSS (> 15–18) • Prior pelvic RT • Prior TURP • large median lobe • Gland volume >60 cc • Inflammatory bowel disease
- 20. What are the advantages of brachytherapy over EBRT? • Decreased integral dose to the patient, particularly to the rectum and bladder, which allows for dose escalation (thanks to inverse square law). • Simplified targeting of RT (i.e., no issues with setup variation, prostate motion, etc.). → No CTV to PTV expansion is required. → Less normal tissue irradiated to high doses of radiation. • Shorter treatment course.
- 21. Dose profiles and target movement
- 22. Margins Matter!
- 23. Prostate Brachytherapy Types Low Dose Rate (LDR) using permanently implanted iodine- 125 (I-125) or palladium-103 (Pd- 103) or Cesium-131 (Cs-131) radioisotopes. High Dose Rate (HDR) using temporarily implanted iridium- 192 (Ir-192) or Cobalt-60 (Co-60) radioisotopes.
- 24. HDR Advantages over LDR (Dose Optimization)
- 25. Radiobiologic advantage of HDR • The inverse square relationship that governs dose distribution results in normal tissues adjacent to the target receiving significantly less than the prescribed dose (e.g., 80% to the bladder and rectum). • At large fraction sizes, the exponential nature of the linear quadratic model creates a greater spread in the BED for normal vs. tumor tissue. A nominal difference of 20% is biologically more than this at large fractions sizes. • For example, if the prostate were to receive 12 Gy but the bladder dose was constrained to receive 10 Gy (a 20% difference), the BED calculated difference is nearly 40%, assuming an alpha/beta ratio of 3. Prostate cancerAlpha/Beta ratio: 1.1 (Less than late responding normal tissues!)
- 26. HDR Brachytherapy • Under spinal anesthesia, 14 HDR brachytherapy steel needle's transperineally implanted in the prostate with TRUS guidance using a template. • 13.5 Gy × 2 fractions (one week apart) prescribed to 100% isodose line.
- 27. Follow up • PSA • 6m after brachytherapy: 3 ng/mL • 1y after brachytherapy: 1 ng/ml • 18m after brachytherapy: 1 ng/mL • 2y after brachytherapy: 2 ng/mL • 30m after brachytherapy: 1.5 ng/mL Biochemical failure?
- 28. PSA Bounce • Is the abrupt rise and fall in the PSA value following BT. • Bounces may occur in 40%–50% of hormone-naïve pts typically 12–30 months after BT, more commonly in younger patients. • PSA bounce does not appear to predict for clinical failure. • Caution is advised when interpreting PSA levels in the first 30 months after BT. Biochemical failure definition (Phoenix consensus): PSA increase by 2 ng/mL or more above the nadir PSA.
- 29. Thank You For Your Time Any Questions?, Comments?