Clinical outcomes among patients treated with Lu-PSMA-617 and metastasis-directed EBRT for metastatic prostate cancer.

Metastasis-directed external beam radiation therapy (EBRT) delivered for limited-volume disease, integrated with systemic radioligand therapy, may improve long-term disease control across the spectrum of metastatic prostate cancer. We examined 88 patients with metastatic prostate cancer who received both lutetium-177 PSMA-617 (LuPSMA) radiopharmaceutical therapy and metastasis-directed external beam radiation therapy (EBRT) between June 2022 and August 2025. EBRT was delivered to a median of three metastatic sites, most commonly bone (69.3 %) and lymph nodes (64.8 %). The PSA50 response rate to LuPSMA was 55.7 %, with a median time to response of 1.6 months. With a median follow-up of 22.1 months, the median overall survival was 20.1 months. Hematologic toxicity was manageable, with grade ≥ 2 anemia in 30.7 % (including one patient with grade 3) and grade ≥ 2 leukopenia in 9.1 % of patients. These findings support the clinical feasibility and tolerability of integrating lesion-directed EBRT with systemic radioligand therapy and suggest that prior focal radiation does not meaningfully compromise tolerability or efficacy of subsequent radiopharmaceutical therapy. Prospective studies are warranted to define optimal patient selection, treatment sequencing, and timing of integration.