Natural history of biochemical recurrence after radical prostatectomy with adjuvant radiation therapy

Purpose: We evaluated the long-term outcome of patients with biochemical recurrence following radical prostatectomy with adjuvant radiation therapy and determined predictors of systemic progression in these men. Materials and Methods: We identified 134 men with biochemical recurrence following radical prostatectomy plus adjuvant radiation therapy for pT_anyN0M0 disease. Median followup was 13.1 years. Survival after biochemical recurrence was estimated using the Kaplan-Meier method. Cox proportional hazard regression models were used to analyze clinicopathological variables associated with systemic progression after biochemical recurrence. Results: Overall, 41 patients (31.5%) with biochemical recurrence experienced systemic progression and 57 (42.5%) died, including 19 (14.2%) of prostate cancer. Median systemic progression-free and cancer specific survival were not attained at 15 years of followup after biochemical recurrence. Median time from prostatectomy to recurrence was 3.3 years. Ten-year cancer specific survival was not significantly different for patients who experienced biochemical recurrence less and greater than 3.3 years after radical prostatectomy (83% and 83%, respectively, p = 0.39). Moreover, on multivariate analysis increased pathological Gleason score (HR 1.78, p = 0.02) and rapid prostate specific antigen doubling time (less than 6-month doubling time HR 11.39, p <0.0001) were significantly associated with the risk of systemic progression. Conclusions: The natural history of biochemical recurrence after radical prostatectomy plus adjuvant radiation therapy is heterogeneous with only a minority of these men experiencing systemic progression and death from prostate cancer. The decision to begin additional therapies in such patients must balance the risk of disease progression, based on pathological Gleason score and postoperative prostate specific antigen doubling time, against the cost and morbidity of treatment.