External validation of the bellmunt risk score for survival prediction in mCRPC patients undergoing [177Lu]Lu-PSMA-617 therapy.

PURPOSE: [177Lu]Lu-PSMA-617 is a standard-of-care therapy for metastatic castration-resistant prostate cancer (mCRPC). Given the heterogeneous clinical responses, accessible prognostic tools are needed. We recently demonstrated that the Bellmunt Risk Score (BRS)-comprising ECOG performance status >0, hemoglobin <10 g/dL, and the presence of liver metastases-predicts overall survival (OS) in a primary mCRPC cohort. This study aims to externally validate the BRS in an independent cohort. METHODS: We retrospectively evaluated 243 mCRPC patients treated with [177Lu]Lu-PSMA-617 at an independent tertiary center. The BRS was calculated at baseline (range 0-3). Endpoints included OS analyzed via Kaplan-Meier estimators, multivariable Cox regression, Harrell's C-index, and time-dependent area under the curve (tAUC). RESULTS: The cohort was distributed into BRS 0 (17.6%), BRS 1 (52.7%), BRS 2 (26.1%), and BRS 3 (2.9%). Kaplan-Meier analysis revealed significant risk stratification, with an estimated median OS of 24.0, 15.8, 11.2, and 8.7 months for BRS 0, 1, 2, and 3, respectively (p < 0.001). In univariable analysis, BRS significantly predicted survival. In multivariable Cox regression adjusted for the number of prior treatment lines, BRS 2 (HR 3.04, p < 0.001) and BRS 3 (HR 4.76, p = 0.002) remained independent predictors of shortened OS. The BRS demonstrated robust predictive accuracy, achieving a tAUC of 71.3% for 1-year OS. CONCLUSION: The BRS is a pragmatic, robust, and easily calculable prognostic tool for mCRPC patients undergoing [177Lu]Lu-PSMA-617 therapy, successfully validated in an independent external cohort.