Renal outcomes following ¹⁷⁷ Lu-PSMA-617 (LuPSMA) in patients with metastatic castration-resistant prostate cancer (MCRPC).

138 Background: LuPSMA is a PSMA-targeted radiopharmaceutical used to treat mCRPC that may impair kidney function, due to PSMA expression on proximal tubular cells and urinary excretion of the radiopharmaceutical. While a short-term decline in estimated glomerular filtration rate (eGFR) has been reported, the incidence of long-term decline, along with clinical and biochemical predictors for decline, has not been well-characterized. Methods: We evaluated consecutive patients with mCRPC treated with ≥3 cycles of LuPSMA at our institution between 6/2022 and 6/2025. Kaplan-Meier and Cox regression models were used to analyze time to eGFR decline, defined as ≥15% decline from baseline eGFR; severity of eGFR decline was further categorized as mild (15-30%), moderate (30-40%), and severe (≥40%). Baseline plasma levels of TNFaR-1, TNFaR-2, YKL-40, MCP-1, and KIM-1 were evaluated in a subset of patients who did (n=23, cases) and did not (n=23, controls) experience ≥15% eGFR decline. Results: 213 patients (median age 72) were included, who received a median of 6 cycles of LuPSMA; median baseline eGFR was 88 mL/min (IQR 73-97). At a median follow-up of 7.1 months (range <0.1-29) after cycle 3, 92 patients experienced eGFR decline; the cumulative incidence was 23% (95% CI 18-29), 33% (26-40) and 42% (33-50) at 3, 6, and 9 months after cycle 3, respectively. Renal recovery (to eGFR ≤15% from baseline) was seen in 61 patients (66%), with a median time to recovery of 1.8 months (95% CI 1.5-2.5). Among those who experienced eGFR decline by 12 months post-treatment initiation (n=73), 45 (62%), 11 (15%), and 17 (23%) had mild, moderate, and severe impairment, respectively; CKD stage distribution at baseline and 12 months are shown in the Table. Hypertension was the only baseline factor associated with eGFR decline (univariable HR=1.55 [1.01-2.38]). While baseline levels of plasma biomarkers were generally higher in cases compared to controls, these differences were not statistically significant (all p>0.1). Conclusions: eGFR decline after LuPSMA was common but generally transient, with <10% of patients progressing to CKD stage 4 at 12+ months. Longer follow-up and broader evaluation of biomarkers may be helpful in identifying patients at risk for long-term eGFR decline. CKD stage (ml/min) Baseline (n=212), % 12 months (n=68), % 1 (>90) 104 (49) 31 (46) 2 (60–89) 86 (41) 22 (32) 3 (30–59) 22 (10) 12 (18) 4 (15–29) 0 3 (4)