Efficacy and safety of [161Tb]Tb-PSMA radioligand therapy in metastatic castration resistant prostate cancer: a systematic review and meta-analysis.

INTRODUCTION: Prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT) using Terbium-161 [161Tb]-labeled compounds has recently been investigated in patients with metastatic castration-resistant prostate cancer (mCRPC). We performed a systematic review and meta-analysis to evaluate the efficacy and safety of [161Tb]Tb-PSMA RLT in this clinical setting. METHODS: We conducted a comprehensive literature search across PubMed/MEDLINE, Embase, and the Cochrane databases to retrieve published articles on the efficacy and safety of [161Tb]Tb-PSMA RLT in mCRPC. Studies reporting the use of [161Tb]Tb-PSMA RLT in mCRPC patients were eligible for inclusion. Pooled estimates of disease control rate (DCR), objective response rate (ORR), and adverse event rate were calculated using a random-effects model. Statistical heterogeneity was assessed using the I2 statistic. RESULTS: Six studies published between 2024 and 2026, including 80 mCRPC patients treated with 291 cycles of [161Tb]Tb-PSMA RLT, were included. Most patients had pretreated disease and had previously received PSMA-targeted radionuclide therapy. The pooled DCR was 83.9% (95% confidence interval [CI]: 76.0-92.0%) with no significant heterogeneity (I2 = 0%). The pooled ORR was 50.2% (95% CI: 27.0-74.0%), although significant heterogeneity was observed (I2 = 81%). Across all studies, 124 adverse events were reported, corresponding to a pooled adverse event rate of 41%, but high grade were only 18. CONCLUSION: Current evidence suggests that [161Tb]Tb-PSMA RLT is a promising therapeutic option for patients with mCRPC, demonstrating encouraging disease control and an acceptable safety profile. Nevertheless, defining its precise role requires larger-scale, comparative trials conducted across multiple centers over longer observation periods.