The purpose of the present study was to examine the outcome profiles of a large number of patients with locally advanced adenocarcinoma of the prostate following radical perineal prostatectomy (RPP) for clinically organ-confined disease. Of 1662 men who underwent RPP performed by a single surgeon between January 1972 and January 1999, 692 patients (41.6%) aged a median of 66.1 years were found to have extracapsular disease on pathological evaluation. The extent of disease was categorized as either specimen-confined (n = 355) or margin-positive (n = 337). The histological grade of the cancer was characterized using the Gleason score. Time to biochemical failure, defined as a prostate-specific antigen (PSA) level of > or = 0.5 ng/ml, and cancer-associated survival were the end points of our outcome analysis using the Kaplan-Meier product-limit method. The median time to cancer-associated death for patients with specimen-confined and margin-positive disease was 18.5 and 13.1 years, respectively. After 5 years, 37% and 54% of the patients with specimen-confined and margin-positive disease, respectively, had PSA failure. Prostate cancer patients with a Gleason score of 5-6, 7, and 8-10 experienced a median time to cancer-associated death of 19.9, 19.2, and 10.5 years, respectively. A subset of patients undergoing adjunctive radiation therapy (XRT) relapsed biochemically after a median period of approximately 18 months. RPP provides a substantial disease-control benefit in patients with specimen-confined cancer. The time to biochemical failure and the time to cancer-associated death are significantly influenced by the biology of the underlying disease, necessitating long-term follow-up in the outcome analysis of any modality of treatment for prostate cancer. A benefit of early adjunctive XRT for local failure remains to be determined.