Association of time to upfront treatment initiation with outcomes in metastatic hormone-sensitive prostate cancer: a 4-month landmark analysis.

BACKGROUND: The clinical significance of variation in the timing of treatment intensification after androgen deprivation therapy (ADT) initiation in metastatic hormone-sensitive prostate cancer (mHSPC) remains unclear. We evaluated whether time to upfront treatment initiation was associated with outcomes in a multicenter cohort. METHODS: In a retrospective study, we performed a 4-month landmark analysis in patients with mHSPC treated with upfront androgen receptor signaling inhibitor-based or taxane-containing regimens who had evaluable CRPC data and complete baseline covariates. The cohort included 1,103 patients, classified as earlier initiation (< 4 months from ADT start; n=1,036) or later initiation (≥ 4 months; n=67). CRPC-free survival (CRPC-FS) and overall survival (OS) were evaluated using Kaplan-Meier and inverse probability of treatment weighting (IPTW)-adjusted Cox analyses. Restricted cubic spline analyses examined the continuous association between treatment delay and outcomes. Sensitivity analysis used a 3-month landmark. RESULTS: In the 4-month landmark IPTW cohort, later initiation was not significantly associated with either CRPC-FS (hazard ratio [HR] 1.05, 95% confidence interval [CI] 0.80-1.37; p=0.737) or OS (HR 0.77, 95% CI 0.45-1.32; p=0.338). Delay distributions differed by regimen, with docetaxel-containing regimens showing longer intervals to upfront treatment. Adjusted spline analyses did not suggest a clear threshold at which longer delay was associated with marked deterioration in CRPC-FS or OS. Results were consistent in the 3-month landmark sensitivity analysis. CONCLUSIONS: Among patients who remained alive and CRPC-free at the 4-month landmark and ultimately received treatment intensification, later initiation was not significantly associated with CRPC-FS or OS.