Long-term hazard of progression after radical prostatectomy for clinically localized prostate cancer: Continued rise of biochemical failure after 5 years

Purpose: Cure from malignancy is commonly defined as a disease-free state lasting 5 years after treatment. We analyzed clinical and biochemical progression rates after radical prostatectomy for men with clinically localized prostate cancer with particular attention to recurrence beyond 5 years. Annual hazard rates of progression were calculated to determine the probability of recurrence at specific intervals following surgery. Materials and Methods: The records of 2,782 men with clinically localized prostate cancer (cT1-T2) undergoing radical prostatectomy between 1987 and 1993 were reviewed. All patients were treated in the prostate specific antigen (PSA) era so that serial followup PSA values were available from the time of surgery. Analysis was limited to patients who did not receive adjuvant treatment within 90 days of radical prostatectomy. Disease progression was defined as documented local recurrence, systemic progression and/or PSA 0.4 ng./ml. or greater. Lymph node positive cases were eliminated from analysis since almost all received adjuvant hormonal therapy. Annual hazard rates for progression were calculated using the formula: [No. events No. patients at risk] x 100. Progression-free survival probabilities were determined using the Kaplan-Meier method. Results: Pathological stage was pT2a-b, N0 (68%), pTSa, N0 (21%) and pT3b, N0 (11%). Biochemical progression-free survival at 5 and 10 years was 76% and 59%, respectively, for the entire study population while those with pathologically organ confined (pT2, N0) cancers had progression-free survival rates of 82% and 68% at 5 and 10 years, respectively. A total of 819 patients (29%) eventually had disease progression, including 160 (6%) with progression after 5 years. Annual hazard rates were highest during the first 2 years after radical prostatectomy for the entire population. Patients with adverse prognostic features (pT3b, PSA 10 ng./ml. or greater, Gleason score 8-10 and nondiploid cancers) had high initial hazard rates that decreased with time to lower levels. Those with pathologically organ confined cancer had low but constant hazard rates throughout followup. Conclusions: Although progression after radical prostatectomy usually occurs early, reflecting the impact of clinical under staging, a significant number of men, including those with organ confined cancers, will continue to have disease progression after 5 years. Patients undergoing radical prostatectomy should be subjected to long-term followup to allow the option of early intervention should progression occur.