Efficacy, safety, and quality of life outcomes of [177Lu] Lu-PSMA radioligand therapy in metastatic castration-resistant prostate cancer: a GRADE-assessed systematic review, meta-analysis and trial sequential analysis
In brief
Lu-177 PSMA radioligand halves radiographic progression in metastatic castration-resistant prostate cancer
In a meta-analysis of six RCTs (2,113 patients), Lu-177 PSMA improved radiographic progression-free survival by about 45% and more than doubled the chance of a PSA response, while delaying quality-of-life decline. Overall survival was not higher in the primary analysis but appeared modestly better after adjusting for crossover. Safety was comparable to standard care, but further trials are needed to define optimal sequencing.
- Journal
- International urology and nephrology (Q2)
- Published
- 8 August 2026
- Study design
- Systematic review / meta-analysis of RCTs
- Evidence level
- Level 1, High (CEBM 1a)
- Authors
- Moosa Mubarika, Muhammad Maaz, Awon Muhammad, Syeda Emmama, Zaroon Mazhar, Muddassir Khalid, et al.
- PMID
- 42570199
- DOI
- 10.1007/s11255-026-05329-4
Why clinicians should know about it
- Picked for Biochemistry (medical) (top studies of the week, 9 August 2026).
- Picked for Urology (top studies of the week, 9 August 2026): Systematic review of Lu‑PSMA therapy in mCRPC
Abstract
BACKGROUND AND OBJECTIVE: Lutetium-177-PSMA radioligand therapy ([177Lu] Lu-PSMA) is an emerging targeted treatment for metastatic castration-resistant prostate cancer (mCRPC). We evaluated the comparative efficacy, safety, and quality-of-life (QoL) impact of [177Lu] Lu-PSMA versus contemporary standard-of-care (SOC) regimens in mCRPC. METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs). Adult participants with PSMA-positive mCRPC (n = 2113) randomized to [177Lu] Lu-PSMA or SOC were included. Primary outcomes were overall survival (OS) and radiographic progression-free survival (rPFS). Secondary outcomes included PSA response, QoL (FACT-P), and adverse events. Treatment effects were pooled using random-effects models. KEY FINDINGS AND LIMITATIONS: Six RCTs were analyzed. Primary intention-to-treat analysis did not demonstrate a statistically significant overall survival improvement (HR 0.81; 95% CI 0.62-1.06); however, sensitivity analysis adjusting for control-arm crossover suggested a survival benefit (HR 0.76; 95% CI 0.59-0.96). [1⁷⁷Lu] Lu-PSMA significantly improved rPFS (HR 0.55; 95% CI 0.43-0.71), PSA response (RR 2.33; 95% CI 1.38-3.93), and delayed QoL deterioration (HR 0.58; 95% CI 0.51-0.66). The intervention increased low-grade xerostomia and grade ≥ 3 thrombocytopenia, though overall severe adverse events were comparable to SOC. Limitations include inter-trial heterogeneity, control-arm crossover diluting ITT estimates, and imaging-based selection bias. CONCLUSIONS AND CLINICAL IMPLICATIONS: [177Lu] Lu-PSMA improves rPFS, biochemical response, and QoL in mCRPC, with an OS benefit apparent after accounting for crossover. These findings support integrating [177Lu] Lu-PSMA into clinical practice. Additional trials are required to determine optimal treatment sequencing and efficacy in taxane-naïve populations. PROSPERO REGISTRATION: The protocol of this systematic review and meta-analysis is registered under PROSPERO, having ID CRD420251151366.
Abstract as published, via PubMed.
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