A phase 3 trial evaluated the efficacy and safety of lutetium-177 (¹⁷⁷Lu)-PSMA-617 in patients with metastatic castration-resistant prostate cancer (mCRPC). The trial enrolled 831 of 1179 patients who had previously received at least one androgen-receptor–pathway inhibitor and one or two taxane regimens, and who had PSMA-positive lesions confirmed by ⁶⁸Ga-PSMA-11 PET-CT. Patients were randomly assigned in a 2:1 ratio to receive ¹⁷⁷Lu-PSMA-617 plus standard care or standard care alone. The primary endpoints were imaging-based progression-free survival (PFS) and overall survival (OS), with hazard ratios of 0.67 and 0.73, respectively. ¹⁷⁷Lu-PSMA-617 significantly prolonged both PFS (median 8.7 vs. 3.4 months) and OS (median 15.3 vs. 11.3 months) compared to standard care. Key secondary endpoints, including objective response, disease control, and time to symptomatic skeletal events, also favored ¹⁷⁷Lu-PSMA-617. Adverse events of grade 3 or higher occurred in 52.7% of patients receiving ¹⁷⁷Lu-PSMA-617, but quality of life was not adversely affected. The trial demonstrated that ¹⁷⁷Lu-PSMA-617, when added to standard care, significantly improved PFS and OS in patients with PSMA-positive mCRPC. The safety profile was consistent with early-phase studies, and the therapy was associated with a low incidence of adverse events leading to dose reduction, interruption, or discontinuation. The trial also showed that ¹⁷⁷Lu-PSMA-617 prolonged overall survival in patients with disease refractory to androgen-receptor–pathway inhibitors and taxane chemotherapy. The addition of ¹⁷⁷Lu-PSMA-617 to standard care was associated with reduced toxic effects, delayed biochemical progression, and improved time to worsening of health-related quality of life and pain. The trial was funded by Endocyte, a Novartis company, and is registered as NCT03511664.A phase 3 trial evaluated the efficacy and safety of lutetium-177 (¹⁷⁷Lu)-PSMA-617 in patients with metastatic castration-resistant prostate cancer (mCRPC). The trial enrolled 831 of 1179 patients who had previously received at least one androgen-receptor–pathway inhibitor and one or two taxane regimens, and who had PSMA-positive lesions confirmed by ⁶⁸Ga-PSMA-11 PET-CT. Patients were randomly assigned in a 2:1 ratio to receive ¹⁷⁷Lu-PSMA-617 plus standard care or standard care alone. The primary endpoints were imaging-based progression-free survival (PFS) and overall survival (OS), with hazard ratios of 0.67 and 0.73, respectively. ¹⁷⁷Lu-PSMA-617 significantly prolonged both PFS (median 8.7 vs. 3.4 months) and OS (median 15.3 vs. 11.3 months) compared to standard care. Key secondary endpoints, including objective response, disease control, and time to symptomatic skeletal events, also favored ¹⁷⁷Lu-PSMA-617. Adverse events of grade 3 or higher occurred in 52.7% of patients receiving ¹⁷⁷Lu-PSMA-617, but quality of life was not adversely affected. The trial demonstrated that ¹⁷⁷Lu-PSMA-617, when added to standard care, significantly improved PFS and OS in patients with PSMA-positive mCRPC. The safety profile was consistent with early-phase studies, and the therapy was associated with a low incidence of adverse events leading to dose reduction, interruption, or discontinuation. The trial also showed that ¹⁷⁷Lu-PSMA-617 prolonged overall survival in patients with disease refractory to androgen-receptor–pathway inhibitors and taxane chemotherapy. The addition of ¹⁷⁷Lu-PSMA-617 to standard care was associated with reduced toxic effects, delayed biochemical progression, and improved time to worsening of health-related quality of life and pain. The trial was funded by Endocyte, a Novartis company, and is registered as NCT03511664.