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 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.)
The PDQ editorial boards use a ranking system of levels of evidence to help the reader judge the strength of evidence linked to the reported results of a therapeutic strategy. For any given therapy, results of prevention and treatment studies can be ranked on each of the following two scales:
Strength of the study design.
Strength of the endpoints.
Together, the two rankings provide a measure of the overall level of evidence. Screening studies are ranked on strength of study design alone...
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 patients.
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 of prostate cancer at the present time.
The Prostate Cancer Prevention Trial (PCPT; SWOG-9217), a prospective, randomized clinical trial of finasteride versus placebo, demonstrated a 25% reduction in prostate cancer prevalence 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%).