¹⁷⁷Lu-PSMA Radioligand Therapy in Metastatic Castration-resistant Prostate Cancer With Complex Renal Conditions: A Case Series.

OBJECTIVE: ¹⁷⁷Lu-PSMA-617 radioligand therapy (RLT) is an established treatment for metastatic castration-resistant prostate cancer (mCRPC). Its predominant renal clearance pathway raises concerns about safety and dosimetry in patients with underlying renal disease. Such patients are typically excluded from clinical trials, leaving a significant evidence gap in clinical practice. The aim of this study is to describe our experience with ¹⁷⁷Lu-PSMA-617 RLT in mCRPC patients presenting with complex pre-existing renal conditions, including end-stage renal disease on hemodialysis, renal transplant, chronic kidney disease, severely reduced glomerular filtration rate, obstructed kidneys, and solitary kidney. METHODS: We retrospectively reviewed cases of mCRPC patients with significant renal comorbidity treated with ¹⁷⁷Lu-PSMA-617 at our institution. Patient demographics, renal function parameters, treatment adaptations, dosimetric data, PSA response, and renal safety outcomes were recorded for each case. RESULTS: Six patients with distinct renal conditions were identified. All patients received at least 2 cycles of ¹⁷⁷Lu-PSMA-617. PSA responses (≥50% decline) were observed in 4/6 patients (67%), ranging from 37% to 99.9% across the cohort. Renal function remained stable or improved in most cases, with individualized dosimetry and multidisciplinary management enabling safe administration. No patient required permanent cessation of therapy due to acute renal toxicity. CONCLUSIONS: With careful patient selection, individualized dosimetry, multidisciplinary input, and close renal monitoring, ¹⁷⁷Lu-PSMA-617 RLT can be administered safely in mCRPC patients with complex renal disease. These cases highlight the need for prospective data and consensus guidelines for this underserved population.