Efficacy and safety of rechallenge therapy with [177Lu]Lu-PSMA in metastatic castration-resistant prostate cancer: a systematic review and meta-analysis

Abstract

Lutetium-177 PSMA radioligand therapy ([¹⁷⁷Lu]Lu-PSMA-RLT) is an effective treatment option for patients with metastatic castration-resistant prostate cancer (mCRPC). Prospective studies reported favourable efficacy and safety outcomes of up to 6 cycles of [¹⁷⁷Lu]Lu-PSMA. This study aimed to evaluate the efficacy and safety of [¹⁷⁷Lu]Lu-PSMA rechallenge therapy in patients with mCRPC who progressed after an initial course of [¹⁷⁷Lu]Lu-PSMA-RLT. This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. A systematic search was performed using relevant keywords in PubMed, EMBASE, and Scopus from establishment to March 2025. Primary endpoints included biochemical responses with a decline in prostate-specific antigen (PSA) of more than 50% and any PSA decline. Secondary outcomes included survival outcomes and treatment-related toxicity following rechallenge therapy with [¹⁷⁷Lu]Lu-PSMA. A random-effects model was used to generate pooled proportions through meta-analysis.