Progression to castration-resistance and metastatic disease following androgen deprivation therapy for biochemical recurrence after prostate cancer surgery

BACKGROUND: Biochemical recurrence after radical prostatectomy for localized prostate cancer impacts nearly one in four patients. While androgen deprivation therapy (ADT) is used in this setting, its impact on metastatic disease outcomes remains unclear in contemporary population-based cohorts. METHODS: We performed a retrospective cohort study using national Veterans Administration electronic health record and Central Cancer Registry data. Men undergoing radical prostatectomy between 2005-2015 were followed through 2019. We defined biochemical recurrence as prostate-specific antigen (PSA) ≥0.20 nanograms/milliliter. We examined biochemically recurrent prostate cancer management and disease progression to castration-resistance and metastatic disease. RESULTS: Of 28,452 men with prostate cancer treated surgically, 7,912 (28%) developed biochemical recurrence with 10.5% developing metastatic disease (median follow up 110 months). Salvage ADT with or without radiation therapy was administered to 24% of patients. In adjusted models, salvage ADT use was associated with worse metastasis-free survival (adjusted hazard ratio (aHR) 1.96, 95% CI 1.71-2.25) and increased castration resistant therapy (aHR 20.51, 95% CI 14.48-29.04). Higher pathologic T stage, Gleason grade group, PSA, nodal involvement, and faster PSA doubling times were predictive of metastasis. CONCLUSIONS: In this large national cohort of men with biochemical recurrence after surgery, most did not develop metastatic disease during nearly 10 years of follow up and one in four patients were treated with ADT. The association between ADT and adjusted outcomes likely reflects more aggressive disease among men selected for hormonal therapy. IMPACT: These findings underscore the importance of continued risk stratification refinement and management optimization for recurrent prostate cancer.