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BACKGROUND: Lutetium-177 PSMA radioligand therapy (¹⁷⁷LuLu-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 ¹⁷⁷LuLu-PSMA. This study aimed to evaluate the efficacy and safety of ¹⁷⁷LuLu-PSMA rechallenge therapy in patients with mCRPC who progressed after an initial course of ¹⁷⁷LuLu-PSMA-RLT. METHODS: 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 ¹⁷⁷LuLu-PSMA. A random-effects model was used to generate pooled proportions through meta-analysis. RESULTS: Eleven studies with 307 patients were included in the final analysis. Of these, 196 received 177Lu-PSMA RLT alone, and 111 received tandem 177Lu/225Ac-PSMA RLT. The pooled proportions of patients with more than a 50% PSA decline and any PSA decline were 0.45 (95% CI: 0.36-0.54) and 0.71 (95% CI: 0.61-0.80), respectively. In a total of 102 patients, 44 (43%) showed low-grade 1-2 xerostomia; however, no cases of serious xerostomia (grade ≥ 3) were reported. Moreover, the pooled proportion of patients experiencing grade ≥ 3 toxicity was 0.14 (95% CI: 0.09-0.19). CONCLUSION: Rechallenge therapy with ¹⁷⁷LuLu-PSMA is a feasible and safe treatment option for late/end mCRPC patients. Tandem approaches with 225AcAc-PSMA may help expand understanding of how to optimize outcomes after ¹⁷⁷LuLu-PSMA progression. However, these findings require confirmation in prospective, randomized studies comparing different rechallenge strategies to define optimal sequencing and patient selection criteria in advanced prostate cancer.
Belabaci et al. (Thu,) studied this question.