Long-Term Nephrotoxicity of¹⁷⁷Lu-PSMA Radioligand Therapy

Abstract

β-emitting ¹⁷⁷Lu 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–¹⁷⁷Lu-PSMA estimated glomerular filtration rate (eGFR) dynamics for at least 12 mo in a cohort of metastatic castration-resistant prostate cancer patients. <b>Methods:</b> The institutional databases of 3 German tertiary referral centers identified 106 patients who underwent at least 4 cycles of ¹⁷⁷Lu-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 ¹⁷⁷Lu-PSMA radioligand therapy was estimated using monoexponentially fitted curves through available eGFR data. eGFR changes were grouped (≥15%–&lt;30%, moderate; ≥30%–&lt;40%, severe; and ≥40%, very severe). Associations between eGFR changes (%) and nephrotoxic risk factors, prior treatment lines, and number of ¹⁷⁷Lu-PSMA cycles were analyzed using multivariable linear regression. <b>Results:</b> 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, <i>P</i> = 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. <b>Conclusion:</b> A considerable proportion of patients may experience moderate or severe decreases in eGFR 1 y from initiation of ¹⁷⁷Lu-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 ¹⁷⁷Lu-PSMA.

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