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Prevention Strategies
Rajesh G. Laungani MDDirector, Robotic Urology
Chairman, Prostate Cancer CenterSaint Joseph’s Hospital, Atlanta
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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
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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!
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Can we prevent prostate cancer?
• PCPT Trial and REDUCE Trial– Finasteride – Dutasteride
• SELECT Trial– Vit E and Selenium
• Statins• Vitamin D
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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)
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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
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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….
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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)
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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
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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
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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
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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
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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
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Thank You