1. Protocols for Advanced Prostate Cancer and/or Local Failure After Radical Prostatectomy Isaac Powell, MD

2. ARS ? ?

3. Case Presentation Local spread outside of the prostate gland with or without positive surgical margins after radical prostatectomy Detectable PSA or rising PSA after surgery

4. Post-op advanced stage

5. Prostate Cancer-Specific Survival

6. D'Amico A, et al. Prostate cancer mortality based on PSADT after surgery. JNCI 2003 Prostate cancer specific mortality <2 mo. <3 <4 <6 <12 PSADT Percent Dead of Prostate Cancer

7. A RANDOMIZED, OPEN LABEL, MULTICENTER, PHASE III, 2-ARM STUDY OF ANDROGEN DEPRIVATION WITH LEUPROLIDE, +/- DOCETAXEL FOR CLINICALLY ASYMPTOMATIC PROSTATE CANCER SUBJECTS WITH A RISING PSA FOLLOWING DEFINITIVE LOCAL THERAPY

8. Schematic of Trial Design Rising PSA following radical prostatectomy PSA doubling time of <9 months Minimum PSA of 1 Testosterone >100ng/ml RANDOMIZE Docetaxel 75 mg/m 2 q 3 weeks x 10 cycles GnRH agonist x 18 months Bicalutamide x 4 weeks GnRH agonist x 18 months Bicalutamide x 4 weeks Arm A Arm B The hypothesis of the study is that Progression Free Servival probability will increase from 50% to 65% a minimum 36 months following randomization.

9. Additional Eligibility Subjects in this group may have no radiographic findings that are clinically suspicious for metastatic disease. Salvage Radiotherapy is allowable and encouraged where appropriate (for example, biochemical recurrence with a positive margin) Version 3.0 / March 24, 2008 Amendment #2

10. Primary Objective Progression Free Survival within the period of 18 months of therapy and at least 18 months follow-up. Progression Free Survival is determined as the time from randomization to: –the first documentation of detectable PSA or –radiographic progression or –to death

11. Secondary Objectives To evaluate cancer specific survival To compare overall survival between the 2 treatment groups Molecular correlates with clinical outcomes –Tissue blocks –Serum/DNA

12. Radiotherapy Protocol After Surgery (closed) Adjuvant Radiotherapy for Pathological T3N0M0 Prostate Cancer Significantly Reduces Risk of Metastases and Improves Survival: Long-Term Followup of a Randomized Clinical Trial Ian M. Thompson,*,† Catherine M. Tangen, Jorge Paradelo, M. Scott Lucia, Gary Miller,‡ Dean Troyer, Edward Messing, Jeffrey Forman, Joseph Chin, Gregory Swanson, Edith Canby-Hagino and E. David Crawford

13. Materials and Methods: A total of 431 men with pT3N0M0 prostate cancer were randomized to 60 to 64 Gy adjuvant radiotherapy or observation. The primary study end point was metastasis-free survival.

14. Figure 1 Metastasis-free survival by treatment arm

15. Conclusions: Adjuvant radiotherapy after radical prostatectomy for a man with pT3N0M0 prostate cancer significantly reduces the risk of metastasis and increases survival.

16. Lymph node metastasis

19. Conclusion Locally advanced prostate cancer plus early aggressive combination therapy equal long term survival and possibly “cure”.