Chemoprevention for prostatic intraepithelial neoplasia

To evaluate the potential application of chemoprevention strategies in prostatic intraepithelial neoplasia.

Review of relevant literature on chemoprevention with emphasis on prostate cancer and premalignant lesions.

Chemoprevention represents a strategy designed to inhibit or reverse the process of carcinogenesis by administering one or several noncytotoxic chemical compounds. The epidemiology of prostate carcinoma indicates that this cancer is a prime candidate for a strategy aimed at prevention due to the extremely high prevalence rate, rising annual incidence, and long latent interval between the cancer-initiating events and the development of invasive disease. Chemopreventive agents may exert their inhibitory effects at different stages of the multistep carcinogenic process broadly categorized as initiation, promotion, and progression. The synthetic retinoids, polyamine synthesis inhibitors, and antiandrogens are among the compounds shown to have in vitro or in vivo chemopreventive effects in prostate carcinogenesis. A major limitation in the evaluation of such agents in a human prostate cancer is the long duration of clinical trials required to assess the efficacy with an endpoint of cancer development. Premalignant epithelial changes such as prostate intraepithelial neoplasia, or PIN, are highly associated with prostate cancer, and share many molecular features of invasive cancer. If the reversal or inhibition of intraepithelial neoplasia translates to a concomitant reduction in clinically relevant prostate cancer, then the pharmacological modulation of PIN may provide a rapid means to evaluate the effects and benefits of potential chemopreventive agents.

Men with PIN may represent ideal candidates for chemoprevention protocols. The ideal agent and duration of therapy remains to be defined.