1. Radiation therapy for Early Stage Prostate Cancer John A. Kalapurakal MD Professor, Radiation Oncology Northwestern University Medical School Chicago, IL

2. ARS ? 1-B

3. RACE/ETHNICITYINCIDENCEMORTALITY All Races 156.9 per 100,000 men 24.7 per 100,000 men White 150.4 per 100,000 men 22.8 per 100,000 men Black 234.6 per 100,000 men 54.2 per 100,000 men Asian/Pacific Islander 90.0 per 100,000 men 10.6 per 100,000 men American Indian/Alaska Native 77.7 per 100,000 men 20.0 per 100,000 men Hispanic 125.8 per 100,000 men 18.8 per 100,000 men It is estimated that 217,730 men will be diagnosed with and 32,050 men will die of cancer of the prostate in 2010 (SEER DATA)

4. Anatomy

6. Risk stratification of Prostate Cancer Low risk T1c-T2a and PSA<10 and Gleason score <6 Intermediate risk T2b-T2c or PSA 10-20 or Gleason score 7 High risk T3-T4 or PSA >20 or Gleason score 8-10

7. Low-risk Prostate Cancer External beam RT: (x-rays, protons) – 70.2Gy-79.2Gy in 39-45 sessions (5 treatments/week, 8-9 weeks) – 3D Conformal, Intensity Modulated RT, Protons Brachytherapy: I-125 (Iodine), Pd-103 (Palladium) – 144Gy in single session

8. Intermediate-risk Prostate Cancer External beam RT: (x-rays, protons) – 75.6-79.2Gy in 42 sessions (5 treatments/week, 8-9 weeks) – 3D Conformal, Intensity Modulated RT (IMRT), Protons External beam RT + Short term Hormone therapy (6-8 months) External beam RT + Brachytherapy: I-125 (Iodine), Pd- 103 (Palladium) – 45 Gy in 25 sessions (5 weeks) + brachytherapy (seeds, HDR)

10. Image Guided RT (IGRT) ALL MODERN RT DELIVERY SHOULD BE IGRT Improve accuracy of treatment Track daily position of the prostate before delivering RT Fiducial markers (x-rays), ultrasound scans, electromagnetic tracking, CT scans (cone beam CT, fiducials), endorectal balloon (x-rays, CT scan)

11. 3D conformal versus IMRT versus Protons

12. Prostate Seed Implantation: Indications, Techniques and Outcomes

15. Post Implant CT scan dosimetry

16. Long-term results: Brachytherapy alone (Low-risk) and RT+Brachytherapy in intermediate-risk Prostate Cancer IJROBP 2010 IJROBP 2007

17. Higher RT dose (79.2Gy) resulted in higher PSA control in low and intermediate-risk prostate cancer without any increase in toxicity JCO 2010 Low riskIntermediate-risk

18. Harvard Study: Adding 6 months of hormones to RT improved survival in intermediate-risk and high-risk disease Intermediate-riskHigh-risk IJROBP 2010

19. MD Anderson Study: Higher RT dose (78 Gy) for intermediate-risk patients resulted in better PSA control and cancer–specific survival IJROBP 2010

20. Low-intermediate risk Prostate Cancer: RTOG 94-08 Study T1b-T2b, PSA <20 RT: 66.6Gy + 4 months of hormone therapy 1979 patients randomized Overall survival significantly better RT+ hormones (51% vs. 4%) PSA control significantly higher with RT+ hormones in low and intermediate risk patients Subset analysis: survival benefit mainly for higher GS and PSA Final results awaited IJROBP 2009

21. Radiation-related Side Effects Likely – Increased urinary frequency, burning and urgency – Increased bowel frequency, burning and urgency – Fatigue Less likely – Rectal bleeding, urinary bleeding – Chronic bowel/bladder symptoms – Temporary blockage of urination requiring a catheter Rare but serious – Permanent Rectal and Bladder injury requiring surgery

22. Hormone-related Side Effects

23. Conclusions – RT for Early Prostate Cancer Best Results: Higher tumor RT doses with improved technology treatments (Brachytherapy, IMRT, Proton therapy) Role of hormone therapy with RT in low and intermediate-risk patients remains to be defined Stereotactic Body Radiotherapy (SBRT): Cyberknife, Linear Accelerator, Tomotherapy Role of hypofractionated RT (70 Gy in 28 fractions, 50Gy in 5 fractions) ? Role of protons PATIENTS CHOICE: Surveillance vs. Surgery vs. Radiation* vs. Seeds

24. Radiation therapy for Early Stage Prostate Cancer John A. Kalapurakal MD Professor, Radiation Oncology Northwestern University Medical School Chicago, IL