Prostate-Specific Antigen Doubling Time Kinetics following Radical Prostatectomy to Guide Need for Treatment Intervention: Validation of Low-Risk Recurrences

SIMPLE SUMMARY: Biochemical recurrence following radical prostatectomy is concerning but does not accurately predict cancer progression or death. In our patients with a biochemical recurrence, we explore whether PSA doubling time kinetics can safely guide avoidance of treatment, preventing unwanted side effects and costs. In our study, initial PSADT and subsequent DT patterns were the only predictors of no need for treatment. Gleason grade group, pathological stage, preoperative PSA, and age were not significant predictors of treatment. Approximately one-third of BCRs observed in this cohort following RP were determined to be low-risk and able to be safely followed without treatment using PSADT kinetics, with a 100% cancer-specific survival after 7.6 years of follow-up. ABSTRACT: Biochemical recurrence (BCR) following radical prostatectomy (RP) has a limited ability to predict prostate cancer (PC) progression, leading to overtreatment, decreased quality of life, and additional expenses. Previously, we established that one-third of men with BCR in our group experienced low-risk recurrences that were safely observed without treatment. Our retrospective cohort analysis of 407 BCR patients post RP validates the use of PSA doubling time (DT) kinetics to direct active observation (AO) versus treatment following RP. The primary outcome was no need for treatment according to the predictive value of models of ROC analysis. The secondary outcome was PC-specific mortality (PCSM) according to Kaplan–Meier analysis. A total of 1864 men underwent RP (June 2002–September 2019); 407 experienced BCR (PSA > 0.2 ng/dL, ×2), with a median follow-up of 7.6 years. In adjusted regression analysis, initial PSADT > 12 months and increasing DT were significant predictors for AO (p < 0.001). This model (initial PSADT and DT change) was an excellent predictor of AO in ROC analysis (AUC = 0.83). No patients with initial PSADT > 12 months and increasing DT experienced PCSM. In conclusion, the combination of PSADT > 12 months and increasing DT was an excellent predictor of AO. This is the first demonstration that one-third of BCRs are at low risk of PCSM and can be managed without treatment via DT kinetics.