Prevention Strategies

Rajesh G. Laungani MDDirector, Robotic Urology

Chairman, Prostate Cancer CenterSaint Joseph’s Hospital, Atlanta

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

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!

Can we prevent prostate cancer?

• PCPT Trial and REDUCE Trial– Finasteride – Dutasteride

• SELECT Trial– Vit E and Selenium

• Statins• Vitamin D

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)

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

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….

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)

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

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

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

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

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

Thank You