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.)
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%).
The concern over the reported increase of high-grade prostate cancer in the finasteride arm compared with the placebo arm (6.6% of men analyzed vs. 5.1%, respectively, P = .005) in the original report from the PCPT was recently reanalyzed with consideration of possible biases that may have influenced these findings. These biases included improved sensitivity of the PSA and digital rectal exam (DRE) for overall prostate cancer detection with finasteride, improved sensitivity of PSA for high-grade prostate cancer detection with finasteride, differences in participants reaching the study endpoints between the two arms, and increased detection of high-grade disease with finasteride due to reduction in size of the prostate gland. Using a bias-adjusted statistical modeling analysis, 7,966 participants in the finasteride arm and 8,024 participants in the placebo arm of the PCPT were studied. No statistically significant difference was found in the overall prevalence of high-grade prostate cancer with finasteride compared with placebo (4.8% vs. 4.2%, respectively, P = .12). Further analysis in a subset of men with a prostate cancer diagnosis who were treated with radical prostatectomy (n = 500) revealed that men on finasteride had less high-grade prostate cancer than men who took placebo (6.0% vs. 8.2%, respectively). The estimated risk reduction for high-grade prostate cancer from this subset analysis in men who had a prostatectomy and took finasteride was 27% (relative risk [RR], 0.73; 95% confidence interval [CI], 0.56–0.96; P = .02).