1. Prevention with Finasteride Ian M. Thompson, MD October, 2009

2. F/U q3mo x 7yr Annual DRE & PSA Biopsy for cause End of Study Biopsy Enrollment Placebo Finasteride Randomization The Prostate Cancer Prevention Trial

3. Placebo 0 z 4.0 Finasteride Placebo Finasteride Placebo Index Index Index Index Finasteride X% X% PSA Index PSA(ng/ml)

5. Total Number of Cancers by Gleason Score 25% Risk Reduction Thompson et al, NEJM 349:215, 2003

6. Concerns Regarding PCPT

7. It now appears that increased sensitivity of detection may have led to increase in HG tumors Finasteride: -Increases ability of PSA to detect cancer and aggressive cancer. -Increases ability of DRE to detect cancer -Improves ability of prostate biopsy to detect cancer and to detect aggressive cancer.

8. AUC finasteride = 0.757 AUC placebo = 0.681 p<.001 Placebo Finasteride Thompson JNCI 2006;98:1128

9. AUC finasteride = 0.886 AUC placebo = 0.824 Placebo Finasteride Thompson JNCI 2006;98:1128

10. Finasteride improves sensitivity of PSA PSA Placebo PSA Finasteride Specificity Sensitivity Placebo Sensitivity Finasteride Cancer vs. No Cancer 4.11.692.7%24%37.8% Gleason >7 versus other 4.11.690.5%39.2%53% Journal of the National Cancer Institute, 2006;98

11. Sensitivity Finasteride Placebo p-value Outcome Prostate CA 21.3% 16.7% 0.013 Gleason > 7 26.1% 21.7% 0.25 Gleason > 8 38.3% 36.4% 0.86 No decrease in specificity with finasteride. Journal of Urology 2007;177:1749-52. Finasteride improves sensitivity of DRE

12. Impact of smaller prostate on sensitivity of biopsy for HG disease 50% 70% p =.01

13. Redman Modeling of Actual Cancer rates Cancer RR=0.70 (0.64, 0.76) p <.0001 Gleason ≤ 6 RR=0.68 (0.57, 0.82) p <.0001 Gleason ≥ 7 RR=0.72 (0.55, 0.94) p <.02 8.2% 6.0% 8.7% 12.9%

14. Conclusions Finasteride significantly reduces risk of cancer. High grade cancer detection may be increased through improved biomarkers and biopsy. (could be additional benefit) Relative risk reduction - > 25% Absolute risk reduction – depends on definition. As great as 7%, as low as 2%.