Precursors of prostate cancer

High-grade prostatic intraepithelial neoplasia (PIN) is the only accepted precursor of prostatic adenocarcinoma, according to numerous studies of animal models and man; other proposed precursors include atrophy and malignancy-associated changes (with no morphologic changes). PIN is characterized by progressive abnormalities of phenotype and genotype that are intermediate between benign prostatic epithelium and cancer, indicating impairment of cell differentiation and regulatory control with advancing stages of prostatic carcinogenesis. The only method of detection of PIN is biopsy because it does not significantly elevate serum prostate-specific antigen concentration and cannot be detected by ultrasonography. The mean incidence of PIN in biopsies is 9% (range, 4%-16%), representing about 115,000 new cases of isolated PIN diagnosed each year in the United States. The clinical importance of PIN is its high predictive value as a marker for adenocarcinoma, and its identification warrants repeat biopsy for concurrent or subsequent carcinoma, especially when multifocal or observed in association with atypical small acinar proliferation (ASAP). Carcinoma develops in most patients with PIN within 10 years. Androgen deprivation therapy and radiation therapy decrease the prevalence and extent of PIN, suggesting that these forms of treatment may play a role in prevention of subsequent cancer. Multiple clinical trials to date of men with PIN have had modest success in delaying or preventing subsequent cancer.