1. Prevention Strategies Rajesh G. Laungani MD Director, Robotic Urology Chairman, Prostate Cancer Center Saint Joseph’s Hospital, Atlanta

2. Who Is at Greatest Risk? Prostate cancer is almost twice as common in African- American men than in Caucasian men African Americans are more than twice as likely to die when diagnosed than Caucasian men Men with a family history of prostate cancer have a 2-3x higher risk of diagnosis

3. Maintain a Healthy Weight Similar to breast and colon cancer, maintenance of a healthy weight has been shown to reduce the risk of prostate cancer and progression of the disease!

4. Can we prevent prostate cancer? PCPT Trial and REDUCE Trial – Finasteride – Dutasteride SELECT Trial – Vit E and Selenium Statins Vitamin D

5. 5-alpha reductase inhibitors PCPT Trial: Finasteride: 5a reductase inhibitor type 2 Prevalence of prostate cancer reduced by 24.8% (24.4% to 18.4% in those randomized to finasteride vs placebo) Prevalence of gleason 7-10 tumors higher in the finasteride group vs placebo Over-detection bias due to gland shrinkage Prevention of low grade, indolent tumors (gleason sum 6)

6. 5-alpha reductase inhibitors REDUCE Trial: Dutasteride: 5a reductase inhibitor type 1 & 2 23% relative reduction in gleason sum 6 cancers Biopsies performed “for cause” (elevated PSA or abnormal DRE)  16.6% and 16.7% positive in the dutasteride and placebo groups, respectively

7. If I Take Proscar (Finasteride) or Avodart (Dutasteride) Can I Prevent Prostate Cancer? Reduction in the number of men who will undergo prostate biopsies…. PSA more sensitive for detection of high grade tumors…. Using these drugs for prevention may give men a false sense of security due to depressed PSA levels…. This may result in delay in diagnosis until they have higher grade disease with less treatment options….

8. SELECT Trial 35,533 men 427 participating sites, activated July 2001 Follow up of minimum 7 yrs, maximum 12 yrs Double blind study Patients assigned to 4 groups: – Selenium/placebo, Vitamin E/placebo, – Vit E + Selenium/placebo, placebo/placebo August 2001 – June 2004 50 yrs or older (AA men) 55 yrs or older (all other men) PSA 4.0 or less Negative DRE Doses: – Selenium (200Ug/d from L- selenomethionine) – Vit E (400 IU/d rac-a- tocopherylacetate)

9. Results September 2008 – SELECT Trial stopped based on interim analysis and lack of effect Median follow up – 5.46 yrs No differences in cancer endpoints – No difference in prostate cancer incidence between placebo and intervention HAZARD RATIO: – Selenium/Vit E  1.05 (CI: 0.88 – 1.25) – Vit E  1.13 (CI: 0.95-1.35) – Selenium  1.04 (CI:0.87-1.24) – Placebo  1.00

11. STATINS and Prostate Cancer “Statins may lower the risk of prostate cancer and its recurrence after radical prostatectomy.” Finnish Trial: 23,320 men in screening arm Overall prostate cancer incidence decreased by 38% in statin users Eliminated bias related to those men who undergo routine PSA screening Murtola et al Int J Cancer 2010

12. STATINS and Prostate Cancer Thrasher et al - Cancer: June 2008 1319 men – 24 mos follow up for men taking statins – 38 mos follow up for men not taking statins 30% lower risk of biochemical recurrence after radical prostatectomy Those who are on statins presented intially with lower PSA’s and clinical stages, but were older and had higher BMI’s

13. Why Vitamin D? Men living in northern latitudes with less sunlight  higher prostate cancer mortality Prostate cancer more common in older men in whom Vit D deficiency is more common African American men  skin melanin blocks ultraviolet radiation and inhibits activation of Vit D Prostate cancer cells express Vit D receptors – Several studies demonstrate antiproliferative effect of Vit D on prostate cancer cell lines

14. What should I do to prevent prostate cancer? Education Awareness Understanding risks Statins show promise Selenium and Vit E  no effect 5a reductase inhibitors  continued debate

15. Thank You