Localized prostate cancer is the most common cancer in men in Western countries. For patients with high risk localized prostate cancer, the current recommended treatment is androgen deprivation therapy combined with radiotherapy. Several large randomized controlled trials have shown this combination prolongs progression-free and overall survival compared to androgen deprivation alone. Additional treatment options for high risk localized prostate cancer currently being investigated include radical prostatectomy and chemotherapy with docetaxel. Erectile dysfunction is a common side effect of treatment that can be addressed with oral phosphodiesterase inhibitors or intracavernosal injections.

1. Localized prostate cancer Karim Fizazi, MD, PhD Department of Cancer Medicine Institut Gustave Roussy Villejuif, France

4. Radical prostatectomy Resection of the prostate + seminal vesicles +/- pelvic lymph node dissection

5. Laparoscopic prostatectomy

6. Conformal radiotherapy

7. Collimateur Multi Lames

14. Radiologic assessment Bone scan? Yes : high risk of bone metastases CT scan of the abdomen/pelvis? Yes : Lymph nodes MRI of the prostate? To be discussed if changes treatment decision

16. Preoperative Kattan nomogram Stephenson, JNCI 2006, 98: 715-7

17. Nomogram for patients receiving RT + Hormone therapy Parker CC, Br J Cancer 2002, 86: 686-91

18. What to do? You should have a prostatectomy ! No ! Radiation therapy ! Yes, but they also talk about hormones

19. Prostatectomy? Radiotherapy? Hormone therapy? Chemotherapy? Pelvic lymph node dissection? High risk localized prostate cancer

20. Prostatectomy? Radiotherapy? Hormone therapy? Chemotherapy? Pelvic lymph node dissection? High risk localized prostate cancer

22. Prostatectomy? Radiotherapy? Hormone therapy? Chemotherapy? Pelvic lymph node dissection? High risk localized prostate cancer

24. Prostatectomy? Radiotherapy? Hormone therapy? Chemotherapy? Pelvic lymph node dissection? High risk localized prostate cancer

26. Should radiotherapy be added if endocrine therapy is used?

28. SPCG-7— Endocrine Therapy Alone Versus Endocrine Therapy Plus Radiotherapy HR: 0.44 (0.3 – 0.6) P < .001 HR: 0.68 (0.5 – 0.9) P < .001 Widmark et al. Lancet 2009; 373: 274-6 Death from prostate cancer Overall mortality

29. NCIC CTG PR.3/ MRC PR07/ SWOG JPR3: OS Warde ASCO 2010 320 Deaths, 175 ADT alone, 145 RT+ADT HR=0.77 (95% C.I. 0.61-0.98) P=0.0331 # at Risk ADT ADT+RT ADT ADT+RT Percentage 0 20 40 60 80 100 0 3 6 9 602 603 509 512 Time (Years) 213 232 51 60 7 yr OS 74% 7 yr OS 66%

30. Should radiotherapy be used if the primary local treatment is radical prostatectomy?

31. Radiotherapy as adjuvant to radical prostatectomy 3 randomized phase III trials showing a benefit on PFS German trial (Wiegel T, ASCO 2005) EORTC 22 911 trial (Bolla, Lancet 2005, 366: 572-8) SWOG trial (Thompson, JAMA 2006, 296: 2329-35) Met-free: 83% vs 61% (at 10y) OS : HR 0.76

32. Prostatectomy? Radiotherapy? Hormone therapy? Chemotherapy? Pelvic lymph node dissection? High risk localized prostate cancer

35. Short-term or Long-term ADT combined with radiotherapy?

36. Long-Term ADT prolongs clinical PFS Long-term ADT (n = 487) Short-term ADT (n = 483) Time, years 0 1 2 3 4 5 6 7 8 9 0 10 20 30 40 50 60 70 80 90 100 HR= 1.93, P <.0001 Patients alive, % Bolla, ASCO 2007, Abstr 5014

37. Long-Term ADT prolongs OS Time, years 0 1 2 3 4 5 6 7 8 9 0 10 20 30 40 50 60 70 80 90 100 Long-term ADT (n = 487) Short-term ADT (n = 483) P = .019 (H0: Long ADT superior) HR: 1.43 P = .6543 (H0: Short ADT non-inferior) Patients alive, % Bolla, ASCO 2007, Abstr 5014

38. Prostatectomy? Radiotherapy? Hormone therapy? Chemotherapy? Pelvic lymph node dissection? High risk localized prostate cancer

40. High risk prostate cancer GETUG 12 trial ADT (3 years) + RXT Docetaxel + Estramustine (4 cycles) RANDOMI ZE Primary endpoint: Progression-free survival n = 413/400 pts Stratification - Gleason  8 - PSA>20 - T3 - pN+ / pN- ADT (3 years) + RXT

41. Phase III trials of Docetaxel in localized prostate cancer Ongoing 636 RP Montgomery (USA) VA # 553 CAP Early enrolment termination 228 /1700 RP M. Eisenberger (USA) TAX 3501 Accrual completed 600 XRT H. Sandler (USA) RTOG 0521 Ongoing 396 RP Ahlgren (Sweden) AdPro Accrual completed 413 / 400 XRT K. Fizazi (France) GETUG 12 Ongoing 350 XRT A. D’Amico (USA) DOCET-L-02357 Ongoing 750 RP Eastham (USA) CALGB 90203 Ongoing 924 XRT Kellokumpu-Lehtinen (Fin) AdRad Status # patients ( enrolled /planned) Local treatment PI Study name

42. Mr Leo tolerated well his treatment… … but he’s getting upset … with treatment-induced erectile dysfunction … and his wife as well. Coming back to our patient

45. Thank you !