To establish a model for preoperative counseling and postoperative outcome in patients who choose radical perineal prostatectomy for the clinically localized prostatic malignancy, the following postulates have been identified: (1) the use of preoperative prostate specific antigen (PSA) and Gleason Sum at the time of biopsy can be used to segregate the outcome among patients with Gleason Sum 2 through 6, 7, and 8 through 10. (2) Postoperative PSA levels are excellent surrogate endpoints for defining disease control. (3) The biology of the primary malignancy defines the interval of death after recurrence. A total of 1242 men with the median age of 65.2 years who had Stage cT 1-2 NOMO disease underwent radical perineal prostatectomy. The final pathologic specimen was characterized with regard to disease extent and Gleason Sum. Patients were followed at 2 weeks, 2 months, and then at 6-month intervals for biochemical, physical, and radiographic evidence of disease recurrence. Outcome was evaluated by determining time to biochemical failure (PSA 0.5 ng/ml or greater) or cancer associated death (death with a detectable PSA independent of treatment). Median time to non-cancer death was 19.3 years. Median cancer-associated death endpoints were not reached by patients with organ confined disease. Results were 17.7 years for specimen confined disease and 12.7 years for margin positive disease. At 5 years, 8, 35, and 65% of patients with organ confined, specimen confined, or margin positive disease, respectively, had PSA failure. This served as an excellent surrogate endpoint, preceding cancer associated death by 5-12 years, depending on the biological aggressiveness predicted by Gleason Sum. When segregated by Gleason Sum 2 through 6, 7 or 8 through 10 at the time of biopsy, there was a distinct differentiation in survival among these Gleason Sum classifications according to the PSA at the time of biopsy. This study confirms our postulates and provides guidelines for preparing different therapies among institutions. It also emphasizes that enthusiasm for new treatments may be based on insufficient follow-up. PSA is an excellent surrogate endpoint and it is valuable in segregating patients prior to therapeutic selection and predicting outcome.
