1. Surrogate End point for Prostate Cancer- Specific Mortality After RP or EBRT A D’Amico J Nat Ca Inst 95,18 1376-1383. 2003

2. Background PSA recurrence post local treatment can lead to secondary therapy Is PSA recurrence is surrogate end point for CAP specific mortality

3. Background Short post treatment PSA-DT correlates with time to distant recurrence after PSA failure Short PSA-DT is surrogate end point for CAP death

4. Patients & Methods 8669 Patients from 2 data bases 5918 RP 2751 EBRT Between Jan 1 1988- Jan 1 2002

5. Patients & Methods 3 months neoadjuvant ADT in RP Median age: 64.5 years RP 71.1 years RT

6. Staging DRE PSA TRUS prostate biopsy Gleason score Pre 1996- CT & bone scan

7. Follow-up Entire Cohort Median FU RP: 7.1 yrs Median FU RT: 6.9 yrs PSA –defined recurrence RP 4.1 yrs RT 3.8 yrs 154 deaths, 110 from CAP

8. PSA-DT Minimum of 3 measurements Minimum separation 3 months PSA increase > 0.2ng/mL Post RP <0.2 (0), 0.3, 0.6 Post RT 0.6, 0.9, 1.2, 1.8

9. Results 611(5918) post RP patients had PSA- defined recurrence 840(2751) post RT patients had PSA defined recurrence 12% & 20% respectively had PSA DT < 3 months

10. Results Statistically significant variables include: Age at time of PSA defined recurrence PSA-DT < 3 months Treatment modality not significant

11. Conclusion Post treatment PSA-DT < 3 months is a surrogate end point for CAP specific mortality

12. Preoperative PSA Velocity and the Risk of Death from Prostate Cancer after Radical Prostatectomy W. Catalona et al NEJM July 8 2004

13. Background To evaluate whether prostate cancer specific mortality can be predicted from variables present at diagnosis

14. Methods Clinical information collected prospectively- 1804 underwent RP January 1 1989- June 1 2002 T1C & T2

15. Methods Exclusions: 689 single preoperative PSA 20 adjuvant radiotherapy 1095 study cohort No adjuvant hormonal treatment

16. Methods Median age 65.4 yrs (43-83) 71% T1c 95% PSA < 10ng/mL Median PSA4.3ng/mL PSA Velocity > 2ng/mL 143,65 and 54 men diagnosis after 1,2 or 3 biopsies

17. Follow up Median FU 5.1 years No patient lost to FU Disease recurrence defined as 2 consecutive detectable PSA 366 recurrences & 84 deaths; 27 from CAP

18. Statistical Analysis PSA closest in time before diagnosis & all other values within 1 year PSA velocity in year before diagnosis

19. Results PSA Velocity > 2ng/mL Reduced time to recurrence Death from CAP Death from any cause

20. Results: PSA V > 2ng/mL Associated with increased LN mets Advanced pathological stage High grade disease

21. Discussion PSA Velocity > 2ng/mL Enrolement in clinical trial 28% died of CAP in 7 years Watchful waiting not good option

22. Radical Prostatectomy versus Watchful Waiting in Early Prostate Cancer J. Johansson NEJM May 2005

23. Background Initial results in 2002 Followup data- 10 year results Risk of death due to CAP reduced by 50% Distant metastasis 37% No stat sig reduction in mortality

24. Methods Prospective randomised trial comparing RP versus watchful waiting 1989 – 1999 695 men from 14 centres

25. Methods Age < 75 years Clinical T2 or less Life expectancy >10years Well - moderately differentiated CAP Bone scan –ve PSA < 50ng/mL

26. Methods RP group all underwent LN dissection Proceeded only if negative WW group TURP Hormonal treatment if evidence of local progression or dissemination

27. Follow up PSA Bone scan CXR Cause of death - patient files Local Progression WW: palpable or LUTS necessitating treatment

28. Results 347 RP & 348 WW 76% T2 12% T1c By 2003 21 in RP had no surgery 43 in WW curative surgery LN mets 23

29. Results Death from CAP RP: 30 WW: 50 Death from other causes 50 vs 56 Among Non CAP death 8 vs 1 – mets 13 vs 6 Local progression Death from any cause 106 vs 83

30. Discussion 10 year disease-specific & overall mortality stat significant Incidence of mets lower in RP group Reduction in disease-specific greatest <65 years

31. Conclusion Relative CAP death reduction by 44% 26% overall mortality 40% distant metastasis 67% local progression