PSA Response as a Prognostic Marker in Metastatic Hormone-sensitive Prostate Cancer: Comparison with Tumor Volume (CHAARTED)

Abstract

BACKGROUND AND OBJECTIVE: Tumor volume and prostate-specific antigen (PSA) response (PSAr) are among the most relevant clinical prognostic factors in metastatic hormone-sensitive prostate cancer (mHSPC). However, their comparative prognostic performance has not been evaluated. We aimed to compare the prognostic value of tumor volume and 6-mo PSAr for progression and mortality in patients treated with doublet therapy. Recent data suggest that patients with high-volume (HV) disease achieving a PSAr may experience better outcomes than those with low-volume (LV) but poor PSAr. METHODS: Multicenter retrospective study of patients with mHSPC who were treated with doublet therapy between 2017 and 2025. PSAr at 6 mo was categorized as complete response (CR; PSA ?0.2 ng/ml) or non-response (NR; PSA >0.2 ng/ml). Outcomes included progression-free survival and overall survival. Prognostic performance was assessed using Kaplan-Meier survival estimates and multivariable Cox regression. RESULTS AND LIMITATIONS: A total of 777 patients were included (median age 72 yr [p25-p75: 66-77 yr], of whom 47% had HV disease. The overall median follow-up for the entire cohort was 29 mo (p25-p75: 11-42 mo), whereas among patients without events, the median follow-up was 25 mo (p25-p75: 15-37 mo). The NR/HV group had the highest progression rate (n = 46), followed by NR/LV (n = 12). In contrast, CR with LV and HV showed substantially lower progression rates (n = 21 and 20, respectively). In multivariable Cox analysis, lack of PSAr was strongly associated with increased mortality (hazard ratio [HR] 4.11; 95% confidence interval [CI] 2.44-6.91; p < 0.001), whereas high tumor volume showed a more modest association (HR 1.78; 95% CI 1.02-3.09; p = 0.042). CONCLUSIONS AND CLINICAL IMPLICATIONS: PSAr at 6 mo is a robust prognostic marker in patients with mHSPC treated with doublet therapy. Failure to achieve an early PSAr was associated with a higher mortality risk than high tumor burden alone. Integrating PSAr with tumor volume improves prognostic discrimination. However, given that the aim of this study is not to inform treatment decisions, these findings do not have direct clinical implications and should not be used to guide management. Instead, they may serve as a basis for future research aimed at refining prognostic stratification in this patient population.