Kidney impairment post 177Lu-PSMA radioligand therapy in metastatic prostate cancer.

Abstract

Prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT) is a novel theranostic approved for the treatment of metastatic castration-resistant prostate cancer. It has been understood to have a low risk of mild nephrotoxicity, although the emergence of delayed or acute renal toxicity is variably described. The increasing use of PSMA-RLT as an earlier line of therapy has prompted a review of its renal safety. Given substantial heterogeneity in study design, follow-up, and outcome definitions, findings were synthesized narratively following the Synthesis without Meta-analysis guideline rather than pooled quantitatively. Studies were grouped by evidence hierarchy (randomized, prospective single-arm, retrospective/real-world, and case report/series) before synthesis. Risk of bias was assessed using design-appropriate tools (Cochrane Risk of Bias 2; a five-domain quality-scoring rubric; Joanna Briggs Institute principles for case reports). A review of 45 papers demonstrated mild nephrotoxicity (estimate glomerular filtration rate: 30-12 months after the last treatment cycle. While incidence varied, the severity of renal impairment was commonly mild. The true rate of long-term renal injury is potentially underestimated as endpoints are inconsistently defined, baseline CKD risk is variably reported, and follow-up is often short. Future research with extended follow-up periods beyond 12 months is warranted to understand the true rate of CKD development.