Prostate cancer has been the most common visceral malignancy in American men for the last decade. The estimated lifetime risk of the disease in the United States is 16.6% for white men and 18.1% for African-American men, with a lifetime risk of death of 3.5% and 4.3%, respectively. Recently, the National Cancer Institute (NCI) reported that the overall cancer mortality rate decreased between 1990 and 1997, including a reduction of approximately 6% in prostate cancer mortality. Furthermore, Tarone et al reported that the mortality rate for prostate cancer among white men in the United States declined to a level lower than that reported prior to the introduction of prostate-specific antigen (PSA)-based screening in 1987.
These improvements in mortality have been variously ascribed to screening, improvements in therapeutic modalities, earlier and more aggressive therapy, and more appropriate application of hormone manipulation. However, marked disparities in prostate cancer incidence and mortality among various ethnic groups in the United States and around the world highlight the relative lack of knowledge of the genetic, environmental, nutritional, and biological variables important to this disease.[3,4]
Moreover, despite these advances, most men who develop metastatic disease are destined to die of prostate cancer. An ideal method of reducing the mortality and morbidity associated with carcinoma of the prostate would be through primary prevention; ie, either by reducing the number of life-threatening, clinically evident cases or the age-dependent rate of development so that tumors would become evident 5, 10, or 15 years later. As illustrated in the article by Drs. Das and Kaplan, the use of nontraditional dietary supplements is widespread among men with prostate cancer and those who perceive themselves to be at risk, and the willingness to use such agents provides a ripe opportunity for conducting well-controlled clinical trials of these agents.
The Prostate Cancer Prevention Trial
The recognition that the androgenic milieu of the prostate was important in the development of prostate cancer led to the Prostate Cancer Prevention Trial, or PCPT (Southwest Oncology Group [SWOG]-9217), an investigation of finasteride(Drug information on finasteride) (Proscar). A testosterone analog, finasteride competitively inhibits the enzyme 5-alpha reductase (type 2)which converts testosterone to dihydrotestosterone (DHT) in the prostateand causes a profound reduction in circulating and cellular DHT. Finasteride inhibits the growth of prostate cancer cells in vitro and is an active preventive agent in certain prostate-carcinogenesis animal models.
The PCPT is an ongoing phase III, double-blind, placebo-controlled, randomized trial to determine the efficacy of finasteride in reducing the prevalence of prostate cancer. This trial opened in 1993 and easily exceeded the goal of 18,000 randomized men during the planned 3-year accrual period, a fact that demonstrates broad public support for chemoprevention efforts. Men enrolled in the PCPT are currently undergoing end-of-study prostate biopsies, and results are expected in 2004.
Selenium as a Chemopreventive