Retrospective study of efficacy and safety of ¹⁷⁷Lu-PSMA-617 for metastatic castration-resistant prostate cancer in elderly patients

¹⁷⁷Lu-PSMA-617 (LuPSMA) is an approved PSMA-targeted radiopharmaceutical therapy for men with metastatic castration-resistant prostate cancer (mCRPC). Older patients, particularly octogenarians, represent a substantial proportion of men with mCRPC, but were underrepresented in registrational trials of LuPSMA. A multicenter retrospective study evaluated mCRCP patients age 80 years or older who were treated with LuPSMA after chemotherapy from August 2022 to December 2024. The study included 95 patients (median age 83 years) of whom 36 (38%) and 21 (22%) had a history of cardiac disease or chronic kidney disease, respectively. Patients received a median of five cycles of LuPSMA. Median follow-up was 24.1 months (IQR 6.7-28.1). Fifty-two (57%) and 21 (23%) patients achieved a PSA50 and PSA90 response, respectively. Median progression-free survival and overall survival were 7.3 months (95% CI 6.4-8.7) and 13.5 months (9.7-18.8), respectively. Grade ≥3 hematologic toxicities included anemia (20%) and thrombocytopenia (4%); grade ≥3 acute kidney injury occurred in one patient. Fourteen (15%) patients had dose delays, seven (7%) required dose reductions, and ten (11%) discontinued therapy due to toxicity. Thirty-seven patients (39%) were hospitalized during therapy, with intensive care unit-level care required in two patients (2%), and there was one treatment-related death. The authors conclude that LuPSMA had similar outcomes in octogenarians with mCRPC compared with patients on registrational trials.