Renal Function During and After <sup>177</sup>Lu-PSMA-617 Therapy in Patients with Metastatic Castration-Resistant Prostate Cancer.

Abstract

Radiopharmaceutical therapy with 177Lu-PSMA-617 is an established treatment for metastatic castration-resistant prostate cancer. Because the radiotracer is cleared renally, the kidneys receive measurable radiation exposure, requiring routine monitoring of renal function before each treatment cycle and after therapy. Understanding renal function trends during successive cycles, particularly in patients with comorbidities and preexisting renal impairment, is clinically important for treatment planning and safety assessment. This study evaluated renal function stability using longitudinal changes in estimated glomerular filtration rate (eGFR) and serum creatinine during and shortly after therapy. Methods: We retrospectively analyzed 56 patients treated between 2022 and 2025 who received at least 2 cycles of 177Lu-PSMA-617. Renal function was measured at baseline, during each treatment cycle, and 6-8 wk after therapy. Comorbidities such as hypertension and diabetes mellitus were recorded. Changes over time were evaluated using patient trajectory plots and multilevel linear regression to determine trends across cycles. Renal toxicity was graded using Common Terminology Criteria for Adverse Events guidelines. Results: Among 56 patients, 44.6% had normal renal function, 35.7% had mild impairment, and 19.6% had moderate impairment at baseline. Hypertension and diabetes mellitus were present in 96.4% and 60.7%, respectively. After adjustment for these comorbidities, renal function remained stable across treatment cycles. Only 1 patient with moderate baseline renal impairment developed grade 3 renal toxicity. Overall, the eGFR showed no significant cycle-related change. Patients with normal or mild impairment had stable eGFR, whereas those with moderate impairment demonstrated a greater but nonsignificant decline. Serum creatinine was also generally stable, though a significant increase was noted in patients with moderate renal impairment. Conclusion: 177Lu-PSMA-617 demonstrated a favorable short-term renal safety profile, with renal function remaining stable across treatment cycles in patients with normal or mildly impaired baseline kidney function. Patients with moderate baseline impairment showed modest increases in serum creatinine without a significant decline in eGFR. Longer-term studies are warranted to evaluate delayed renal effects.