Evaluation of Time to Metastasis After Prostatectomy as a Prognostic Factor in Patients With Metachronous mHSPC: A Secondary Analysis of the SWOG‐1216 Phase 3 Trial

ABSTRACT Background The prognostic significance of time to metastasis (TTM) following radical prostatectomy in patients with metachronous metastatic hormone‐sensitive prostate cancer (mHSPC) remains uncertain. We performed a secondary analysis of patient‐level data from the phase 3 SWOG 1216 randomized clinical trial to evaluate whether TTM is associated with progression‐free survival (PFS) or overall survival (OS). Methods Among 1279 trial participants, 301 patients with metachronous mHSPC who had previously undergone prostatectomy were included. Participants were randomized to androgen deprivation therapy (ADT) plus orteronel or ADT plus bicalutamide and followed through 2023. TTM was analyzed as both a continuous variable and using categorical thresholds ranging from 1 to 10 years. Multivariable Cox proportional hazards models adjusted for treatment arm, disease burden, Gleason score, performance status, prostate‐specific antigen, age, and prior ADT. Results Of the included patients, 161 received ADT plus orteronel and 140 received ADT plus bicalutamide; 38% had extensive disease. TTM was not associated with PFS when analyzed continuously (hazard ratio [HR], 1.0; p = 0.30) or categorically across any threshold. Similarly, TTM was not associated with OS (continuous HR, 1.0; p = 0.14), with consistent findings across treatment arms. Conclusions In the secondary analysis of SWOG 1216, TTM was not independently associated with survival outcomes in the multivariable analysis. These findings suggest that TTM alone may not provide sufficient prognostic information to guide patient counseling, and treatment decisions after metastatic recurrence.