Visceral metastases, platelet dynamics, and PSA decline: from biomarkers to better outcomes in [177Lu]Lu‑PSMA‑617 therapy in metastatic castration-resistant prostate cancer.

Radioligand therapy with [177Lu]Lu-PSMA-617 constitutes a significant breakthrough in the management of metastatic castration-resistant prostate cancer (mCRPC). However, clinical outcomes remain variable due to the heterogeneity of patient profiles and limitations in current selection criteria. This study aims to identify simple and reproducible predictive factors to optimize therapy and improve patient stratification. Methods: A retrospective analysis was conducted on 109 mCRPC patients treated with [177Lu]Lu-PSMA-617 at the Institut de Cancérologie Strasbourg Europe. Clinical, biological, and imaging parameters were collected, including early biological changes after the first cycle. Survival analyses and regression models were employed to identify prognostic and predictive factors. Results: Visceral metastases (p < 0.001) and a decrease in platelet count above 25% (p = 0.004) between the first and second cycles were significantly associated with reduced overall survival. Furthermore, a decline in PSA levels above 30% following two cycles emerged as a robust predictor of treatment response, markedly affecting both biochemical progression-free survival (p < 0.001) and radiological progression-free survival (p = 0.002). Conclusion: By combining three factors-visceral metastases, platelet count variation, and PSA reduction-patients could be stratified into distinct prognostic groups as early as after the first cycle. These findings pave the way for personalized management and enhanced clinical outcomes for mCRPC patients receiving [177Lu]Lu-PSMA-617.