Quantifying the Renal Impact of [¹⁷⁷Lu]Lu-PSMA-617: A Longitudinal Analysis of Real-World Data from the LUMEN...

This study aimed to clarify the renal safety of [¹⁷⁷Lu]Lu-PSMA-617 for metastatic castration-resistant prostate cancer (mCRPC), addressing emerging reports of nephrotoxicity. Methods: We retrospectively analyzed patients with mCRPC from the real-world LUMEN registry who received 3 or more cycles of [¹⁷⁷Lu]Lu-PSMA-617. The endpoint was the change in estimated glomerular filtration rate (eGFR) over 24 mo, assessed using linear mixed-effects models. Results: Analysis of 261 patients revealed a modest average decline in eGFR of -0.15 mL/min/1.73 m² per month (95% CI, -0.25 to -0.05; P = 0.005), translating to -1.80 mL/min/1.73 m² per year (95% CI, -3.03 to -0.57). The rate of loss accelerated by approximately -0.1 per year per additional gigabecquerel of administered activity (95% CI, -0.18 to -0.01; P = 0.028). Conclusion: [¹⁷⁷Lu]Lu-PSMA-617 is associated with a slight long-term average decline in eGFR. Although this is unlikely to be clinically relevant for late-stage mCRPC, the cumulative dose effect warrants careful monitoring in earlier disease stages.