Long-Term Nephrotoxicity of ¹⁷⁷Lu-PSMA Radioligand Therapy

beta-emitting Lu-177 targeting prostate-specific membrane antigen (PSMA) is an approved treatment option for metastatic castration-resistant prostate cancer. Data on its long-term nephrotoxicity are sparse. This study aimed to retrospectively evaluate post-Lu-177-PSMA estimated glomerular filtration rate (eGFR) dynamics for at least 12 mo in a cohort of metastatic castration-resistant prostate cancer patients. Methods: The institutional databases of 3 German tertiary referral centers identified 106 patients who underwent at least 4 cycles of Lu-177-PSMA and had at least 12 mo of eGFR follow-up data. eGFR (by the Chronic Kidney Disease Epidemiology Collaboration formula) at 3, 6, and 12 mo after Lu-177-PSMA radioligand therapy was estimated using monoexponentially fitted curves through available eGFR data. eGFR changes were grouped (>= 15%-<30%, moderate; >= 30%-<40%, severe; and >= 40%, very severe). Associations between eGFR changes (%) and nephrotoxic risk factors, prior treatment lines, and number of Lu-177-PSMA cycles were analyzed using multivariable linear regression. Results: At least moderate eGFR decreases were present in 45% (48/106) of patients; of those, nearly half (23/48) had a severe or very severe eGFR decrease. A higher number of risk factors at baseline (-4.51, P = 0.03) was associated with a greater eGFR decrease. Limitations of the study were the retrospective design, lack of a control group, and limited number of patients with a follow-up longer than 1 y. Conclusion: A considerable proportion of patients may experience moderate or severe decreases in eGFR 1 y from initiation of Lu-177-PSMA. A higher number of risk factors at baseline seems to aggravate loss of renal function. Further prospective trials are warranted to estimate the nephrotoxic potential of Lu-177-PSMA.