Safety and Efficacy of Lutetium-177 PSMA Therapy for Metastatic Castration-Resistant Prostate Cancer: A Systematic...

Prostate-specific membrane antigen (PSMA)-targeted radioligand therapy using lutetium-177 has emerged as a promising treatment for metastatic castration-resistant prostate cancer (mCRPC). In this systematic review and meta-analysis, the safety and efficacy of PSMA-targeted radioligand therapy (PRLT) using lutetium-177 ([¹⁷⁷Lu]Lu-PSMA) were assessed.

This meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. A detailed searches were conducted across PubMed, EMBASE, Cochrane Library and Scopus for randomized controlled trials (RCTs) on [177Lu]Lu-PSMA radioligand therapy in mCRPC. Prostate-specific antigen (PSA) responses, toxicity profiles, and outcomes including radiographic progression-free survival (rPFS) and overall survival were assessed. Quantitative analyses with Review Manager 5.4 software, using Risk estimates (hazard ratios, RR and OR) and 95% confidence intervals for outcomes in random effects were performed.

Six RCTs involving 2113 patients with mCRPC were included in the meta-analysis. Patients treated with [¹⁷⁷Lu]Lu-PSMA had a significantly higher response to therapy compared to controls based on ≥50% PSA decrease (OR = 4.27; 95% confidence interval [CI]: 2.59-7.06; P < .00001) and objective response rate (ORR) (RR=2.93; 95% CI, 1.62-5.30; P = .0004). [¹⁷⁷Lu]Lu-PSMA reduced the risk of rPFS (HR=0.57; 95% CI, 0.46-0.70; P < .00001). However, no significant impact on overall survival was observed (HR = 0.81; 95% CI, 0.62-1.06; P = .13). No significant difference in grade ≥3 adverse events was reported (RR = 0.85; 95% CI, 0.63-1.15; P = .32).

These findings support the use of [¹⁷⁷Lu]Lu-PSMA for metastatic castration-resistant prostate cancer, demonstrating both safety profile and efficacy. The potential of this therapeutic approach warrants further investigative efforts to optimize treatment methodologies and improve the quality of patient care and the criteria for patient selection.