Androgen deprivation as a strategy for prostate cancer chemoprevention.

Abstract

Androgens are required for the normal development and function of the prostate gland. Prostate cancer and benign prostatic hyperplasia are common in men and develop in an environment of continuous androgen exposure. The utility of androgen deprivation as a treatment for advanced prostate cancer was first demonstrated in 1941 (1), and many new classes of drugs that interfere with androgen production and function have been introduced in recent years. These agents are effective in treating prostate cancer and benign prostatic hyperplasia and may have an important role in chemoprevention. Since 1991, prostate cancer has been the most common noncutaneous cancer and the second leading cause of cancer-related death in men. The major difficulty in treating prostate cancer is the limitation of current tools to accurately predict the behavior of a given tumor. Although many prostate cancers are clinically insignificant and will have an indolent course, others will result in considerable morbidity and mortality. The major dilemma with regard to prostate cancer is determining what men to treat and who would be better served by expectant management (2). Previous efforts (3) have concentrated on treating invasive cancer, often in advanced stages. Other work (4,5) suggests that an evolving multistep molecular and cellular process, known as carcinogenesis, begins years before invasive cancer is detected. Chemoprevention refers to prevention of cancer or reduction of risk in susceptible individuals by administration of natural or synthetic drugs with little or no toxicity that suppress, delay, or reverse carcinogenesis (6,7). Chemoprevention is most effective in the early stages of cancer formation when reversibility may be feasible. In prostatic carcinoma, the time from tumor initiation and progression to invasive carcinoma often begins in men in the fourth and fifth decades of life and extends across decades, allowing sufficient time to halt or to reverse carcinogenesis (8,9).