Is time to castration resistant prostate cancer a potential intermediate end-point for time to metastasis among men initiating androgen deprivation therapy for non-metastatic prostate cancer with rapid PSA doubling time (<9 months)?

Purpose: Metastasis-free survival (MFS) is a surrogate for overall survival (OS) in men with non-metastatic castration-resistant prostate cancer (CRPC), but this endpoint may take years to develop in men with non-metastatic castrate-sensitive disease. The study objective was to examine whether progression to CRPC is a potential intermediate endpoint for developing metastatic disease in patients with biochemical recurrence (BCR) after radical prostatectomy (RP). Materials and methods: Men with BCR following RP who had PSA doubling times (PSADT) < 9 months and no metastasis at the time of initiating androgen deprivation therapy (ADT) (n = 210) were included. The primary objective was to assess the correlation between CRPC-free survival (CRPC-FS) and MFS, and the secondary objective was to assess the correlation between time to metastasis and time to CRPC. Kendall’s Tau was used to test the correlation for the primary and secondary outcomes. Results: The median MFS was 104 months (95% CI: 83–114) and median CRPC-FS was 100 months (95% CI: 80–114). Based on the Kaplan–Meier curve, the greatest difference in time to MFS and CRPC-FS was around 70% free survival, which was reached at 61.2 months for MFS and 49.6 months for CRPC-FS. Kendall’s Tau for the correlation between CRPC-FS and MFS and between time to CRPC and time to metastasis was 0.867 (95% CI: 0.765–0.968) and 0.764 (95% CI: 0.644–0.884), respectively. Conclusions: Given the high correlation between CRPC-FS and MFS, after validation, CRPC-FS may serve as a potential intermediate endpoint in trials for men with BCR initiating ADT following local therapy.