Abstract
Abstract
Real-world comparison of rezvilutamide versus bicalutamide in high-volume metastatic hormone-sensitive prostate cancer (mHSPC) is limited. While the phase III CHART trial established the efficacy of rezvilutamide in a controlled setting, its generalizability to routine clinical practice, particularly in patients excluded from the trial (e.g., those with prior docetaxel exposure), remains uncertain. Multicenter retrospective cohort study of high-volume mHSPC patients receiving ADT plus rezvilutamide or bicalutamide (2021–2024). Propensity-score matching (1:1) yielded 50 patients per group. Calendar year was not included in the primary propensity-score model but was incorporated as a covariate in prespecified sensitivity analyses to address potential treatment-era bias. Primary endpoint: radiographic progression-free survival (rPFS). Rezvilutamide significantly improved median rPFS (25.9 vs. 16.1 months; HR 0.64, 95% CI 0.41–0.98; p = 0.038), time to castration resistance (18.6 vs. 11.4 months; HR 0.61, 95% CI 0.39–0.94; p = 0.026), and time to PSA progression (20.1 vs. 12.9 months; HR 0.57, 95% CI 0.36–0.91; p = 0.018). PSA50 (84% vs. 62%; p = 0.011) and PSA90 (50% vs. 28%; p = 0.022) responses favored rezvilutamide. Overall survival (HR 0.85, 95% CI 0.50–1.43; p = 0.54) and symptomatic skeletal events (HR 0.82, 95% CI 0.44–1.54; p = 0.53) showed numerical benefit without significance. In exploratory analyses of patients with prior docetaxel exposure (24% of each group)—a population excluded from CHART—the rPFS point estimate favored rezvilutamide (HR 0.68, 95% CI 0.30–1.55), though underpowered. Grade ≥ 3 adverse events were comparable (26% vs. 24%). Prespecified CNS-related events, defined using standardized criteria with independent neurologist review, were lower with rezvilutamide (8% vs. 14%). Rezvilutamide plus ADT provides superior disease control to bicalutamide plus ADT in high-volume mHSPC with a favorable safety profile. These real-world findings complement the CHART trial by including populations excluded from the trial, though the modest sample size limits definitive conclusions for subgroups. Longer-term follow-up is needed to confirm survival benefits.