Genetics Of Prostate Cancer
As with any disease process, decisions
about risk-reducing interventions for patients with an inherited predisposition
to prostate cancer are best guided by randomized controlled clinical trials, and
by knowledge of the underlying natural history of the process. Unfortunately,
little is known about either the natural history or the inherent biologic
aggressiveness of familial prostate cancer compared with sporadic forms.
Existing studies of the natural history of prostate cancer in men with a
positive family history are predominantly based on retrospective case series.
Because awareness of a positive family history can lead to more frequent
work-ups for cancer and result in apparently earlier prostate cancer detection,
assessments of disease progression rates and survival after diagnosis are
subject to selection, lead time, and length biases. Refer to the PDQ summary on
Cancer Screening Overview for more information.
Given the paucity of information on the
natural history of prostate cancer in men with a hereditary predisposition,
decisions about risk reduction, early detection, and therapy are currently based
on the literature used to guide interventions in sporadic prostate cancer,
coupled with the best clinical judgment of those responsible for the care of
these patients, with the active participation of well-informed high-risk
There are no definitive studies of primary
prevention strategies in men with a hereditary risk of prostate cancer. Thus,
there are no definitive recommendations that can be offered to these patients to
reduce their risk for prostate cancer at the present time.
The recently published Prostate Cancer
Prevention Trial (PCPT), a prospective, randomized clinical trial of finasteride
versus placebo, demonstrated a 25% reduction in prostate cancer risk among study
participants receiving finasteride. Finasteride administration produced
statistically similar reductions in prostate cancer risk in
family-history–positive (19% decrease) and family-history–negative (26%
decrease) subjects. A subsequent PCPT publication suggested that end-of-study
biopsies in asymptomatic men with serum prostate-specific antigen (PSA) values
consistently lower than 4.0 ng/mL were more likely to detect prostate cancer in
men with an affected first-degree relative (19.7%) versus those with a negative
family history (14.4%).