Outcome and Renal Safety of PSMA-Targeted Radioligand Therapy in mCRPC Patients With Preexisting Impaired Renal Function.

Abstract

This study aims to evaluate the outcome and renal safety of prostate-specific membrane antigen (PSMA)-radioligand therapy (RLT) in patients with metastatic castration-resistant prostate carcinoma (mCRPC) and preexisting renal impairment. Ninety-four patients with preexisting renal impairment were included in this retrospective analysis. Inclusion criterion was a glomerular filtration rate (GFR) of ≤60 mL/min (equivalent to Common Terminology Criteria of Adverse Events [CTCAE] ≥2). Patients underwent either [ 177 Lu]Lu-PSMA-617 RLT exclusively (n = 63) or additionally in augmented manner with [ 225 Ac]Ac-PSMA-617 (n = 31). The median number of administered cycles was 4 (range, 1-16 cycles) with a mean cumulative activity of 29.9 ± 16.3 GBq (range, 6.9-87.2 GBq) [ 177 Lu]Lu-PSMA-617. Main blood parameters of interest were creatinine, cystatin C, and the respective GFR values. Changes in GFR were categorized according to CTCAE v5.0. In the entire cohort, mean best PSA response was -56.73% ± 45.71%, with 63 of 94 patients (67%) experiencing partial remission. The median progression-free survival and overall survival were 6.7 and 14.1 months, respectively. Under PSMA-RLT, 5 of 94 patients (5.3%) improved to CTCAE grade 0, and 23 of 94 (24.5%) improved to CTCAE grade 1. Three of 94 patients (3.2%) improved from CTCAE grade 3 to grade 2, and only 5 of 94 (5.3%) decreased. The majority (58/94 [61.7%]) of patients stayed stable in terms of CTCAE grading. PSMA-RLT is an effective and safe treatment in mCRPC patients with preexisting impaired renal function (CTCAE ≥2). In daily clinical practice, patients should not be categorically excluded from enrolment to PSMA-RLT due to renal impairment.