Fall 2011 - Institute of Medical Science - University of Toronto

FEATURE
Prostate Cancer Prevention
An Overview
Prostate cancer is the commonest non-cutaneous human malignancy and second most
frequent cause of cancer death in males. Recent published data has established that
prostate cancer is preventable. Substantial pre-clinical and epidemiologic studies
have identified antioxidants and other micronutrients as promising agents for prostate
cancer prevention. Key agents currently include vitamin D, lycopene, capsaicin, soy
products, 5ARIs (alpha reductase inhibitors), and dietary and weight modification.
Dr. Laurence Klotz
MD, FACS, FRCSC
Professor of Surgery,
University of Toronto
T
here is increasing evidence
that the evironment plays an important
role in the progression of
prostate cancer. There is a one hundred fold
variation in age-adjusted mortality rates
from prostate cancer between high and low
risk geographic and racial groups. In marked
contrast to this large global variation, autopsy
studies confirm that micro foci of prostate
cancer exist ubiquitously in 42-80% of males
over 50 years. In nations with a high incidence
of prostate cancer deaths, these foci
appear to be characterized by higher volume,
grade and multifocality compared to patients
from nations with low rates of the disease.
Studies of migrating populations reveal that
men from countries with a low incidence
of prostate cancer (i.e. Japan) acquire an increased
incidence rate within 20 years upon
emigration to the West, approaching that of
the host country. A detailed autopsy study in
American trauma victims found that 30% of
men between 30 and 39 had microfocal prostate
cancer 1 leading to the hypothesis that
environmental influences stimulate latent
prostate cancer to progress to biologically
significant disease.
Despite the evidence that substances can help
prevent or slow prostate cancer progression,
not all results have been positive. Vitamin E
and selenium, both of which appeared very
promising in epidemiologic, pre-clinical,
and clinical studies, were evaluated in a huge
prospective randomized trial with prostate
cancer incidence as the primary endpoint.
The SELECT trial randomized 31,000 men
between groups given placebo, vitamin E,
selenomethionine, and the combination.
The study was stopped early after a futility
analysis showed absolutely no difference in
prostate cancer incidence (or, indeed, in any
other cancer rate). Further, there was a modest
but statistically significant increase in diabetes
in the selenium arm. Thus, the current
recommendation is that patients not take
these 2 agents for prostate cancer prevention.
The Prostate Cancer Prevention Trial (PCPT)
and REDUCE trial addressed the role of 5
alpha reductase inhibitors in prostate cancer
prevention. The PCPT trial randomized
18,000 healthy men between finasteride
(5ARI) and placebo. Following 7 years of
treatment, the incidence of prostate cancer
on biopsy was decreased by 24.8% in the
finasteride arm. Importantly, the incidence
of high-grade prostate cancers in the finasteride-treated
patients was increased. The
REDUCE trial tested the preventive value
of dutasteride in 8231 men with an elevated
PSA (an indicator of possible prostate cancer)
and a negative prior biopsy. The results were
similar; a 23% reduction in the risk of prostate
cancer being diagnosed on biopsy after 4
years on the drug compared to placebo. The
initial analysis did not show a significant difference
in high-grade cancer; a subsequent
Photo by Connie Sun
15 | IMS MAGAZINE FALL 2011 PROSTATE CANCER