Standardizing the Definition of Biochemical Recurrence after Radical Prostatectomy—What Prostate Specific Antigen Cut Point Best Predicts a Durable Increase and Subsequent Systemic Progression?

PURPOSE: Multiple definitions of biochemical recurrence for prostate cancer exist after radical prostatectomy, and variation continues in prostate cancer outcome reporting and secondary treatment initiation. We reviewed long-term prostatectomy outcomes to assess the most appropriate prostate specific antigen cut point that predicts future disease progression. MATERIALS AND METHODS: We identified 13,512 patients with cT1-2N0M0 prostate cancer who underwent radical prostatectomy between 1987 and 2010. Single prostate specific antigen cut points of 0.2, 0.3, 0.4 and 0.5 ng/ml or greater, as well as confirmatory prostate specific antigen value definitions of 0.2 ng/ml or greater followed by prostate specific antigen greater than 0.2 ng/ml and 0.4 ng/ml or greater followed by prostate specific antigen greater than 0.4 ng/ml were tested. Continued prostate specific antigen increase after a designated cut point definition was estimated using cumulative incidence. The strength of association between biochemical recurrence definitions and subsequent systemic progression were analyzed using Cox proportional hazard models and the O'Quigley event based R(2) test. RESULTS: At a median postoperative followup of 9.1 years (IQR 4.9-14.3) a detectable prostate specific antigen developed in 5,041 patients and systemic progression developed in 512. After reaching the prostate specific antigen cut point of 0.2, 0.3 and 0.4 ng/ml, the percentage of patients experiencing a continued prostate specific antigen increase over 5 years was 61%, 67% and 74%, respectively, plateauing at 0.4 ng/ml. The strongest association between biochemical recurrence and systemic progression occurred using a single prostate specific antigen cut point of 0.4 ng/ml or greater (HR 36, R(2) 0.92). CONCLUSIONS: A prostate specific antigen cut point of 0.4 ng/ml or greater reflects the threshold at which a prostate specific antigen increase becomes durable and shows the strongest correlation with subsequent systemic progression. Consideration should be given to using a prostate specific antigen of 0.4 ng/ml or greater as the standard biochemical recurrence definition after radical prostatectomy.