Lu-177-PSMA-617 Radioligand Therapy in Metastatic Castration-Resistant Prostate Cancer Patients with a Single Functioning Kidney

摘要

The aim of this study was to assess the safety, tolerability, and effects on renal function as well as therapeutic efficacy of prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (PRLT) using Lu-177-labeled PSMA-617 in patients with metastatic castration-resistant prostate cancer and a single functioning kidney before PRLT. Methods: Sixteen patients (aged 53-78 y; mean age, 64.7 +/- 6.5 y) with a single functioning kidney received PRLT with Lu-177-PSMA-617 between March 2015 and October 2018. All parameters of renal function (serum creatinine, blood urea nitrogen, and electrolytes) were prospectively documented in a structured database and analyzed before each PRLT cycle and in follow-up. Renal function was further quantified by measuring tubular extraction rate (TER) using Tc-99m-mercaptoacetyltriglycine renal scintigraphy. Treatment-related adverse events were graded according to the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. Kaplan-Meier analysis was performed to obtain the progression-free survival and overall survival. Results: The median administered activity was 22.1 GBq (range, 15.4-33.8 GBq). The calculated absorbed radiation dose to the kidney per cycle was 5.3 +/- 2.1 Gy (0.81 +/- 0.32 Gy/GBq). Renal function was already impaired at baseline in 43.7% of patients, including CTCAE grade 1 renal impairment in 25.0% and CTCAE grade 2 in 18.8%. Grade 1 and 2 renal impairment, respectively, were present in 37.5% and 6.3% of the patients after the first PRLT cycle and in 31.3% and 12.5% after the second cycle. No CTCAE grade 3 or 4 nephrotoxicity was observed during or after treatment. There was no significant change in either TER or the ratio of TER to lower-limit TER after the last cycle of treatment (P > 0.05). The median PFS was 8.1 mo based on both the criteria of the European Organization for Research and Treatment of Cancer and RECIST. The median overall survival has yet to be reached with a median follow-up time of 19.3 mo (range, 5.8-45.3 mo). Conclusion: In patients with a single functioning kidney, Lu-177-PSMA-617 PRLT is feasible, seems to be effective, and is well tolerated, without any signs of acute or subacute nephrotoxicity during a mean follow-up of nearly 2 y (and up to 45.3 mo). Further long-term follow-up of this special patient group is warranted.