Rechallenge With 177 Lu-PSMA Radioligand Therapy in Metastatic Castration-resistant and Hormone-sensitive Prostate Cancer : Lessons From a Multicase Experience.

We report 4 patients with metastatic hormone-sensitive (mHSPC) or castration-resistant prostate cancer (mCRPC) treated with 177 Lu-PSMA-617 radioligand therapy (RLT), including rechallenge after disease progression. Initial RLT induced significant PSA declines, pain relief, and radiographic responses. Upon biochemical or clinical progression, rechallenge with additional 177 Lu-PSMA cycles achieved renewed PSA reductions, sustained symptomatic improvement, and favorable safety, with no grade III-IV hematologic or renal toxicities. These cases illustrate the dynamic application of 177 Lu-PSMA across disease stages and suggest that prior exposure does not preclude subsequent retreatment, supporting the feasibility and efficacy of RLT rechallenge in both mCRPC and mHSPC settings.