Download Prevention Strategies

Prevention Strategies
Rajesh G. Laungani MD
Director, Robotic Urology
Chairman, Prostate Cancer Center
Saint Joseph’s Hospital, Atlanta
Who Is at Greatest Risk?
• Prostate cancer is almost
twice as common in AfricanAmerican 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
• August 2001 – June 2004
• 50 yrs or older (AA men)
• 55 yrs or older (all other
men)
• PSA 4.0 or less
• Negative DRE
• Patients assigned to 4
groups:
– Selenium/placebo,
Vitamin E/placebo,
– Vit E +
Selenium/placebo,
• Doses:
placebo/placebo
– Selenium (200Ug/d from Lselenomethionine)
– Vit E (400 IU/d rac-atocopherylacetate)
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