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

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-<90 mL/min/1.73m2) post-PSMA-RLT. Where chronic kidney disease (CKD) developed, it was either delayed in onset and progressive over time. There was broad heterogeneity of patient cohorts, methodologies, and data quality. In addition, there was limited long-term follow-up data regarding chronic nephrotoxicity, with only five studies having follow-up periods >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.