Health-related Quality of Life in mCRPC Patients Undergoing [161Tb]Tb-PSMA-617 Radioligand Therapy: Pilot Experience From a Real-World Setting

Abstract Purpose PSMA RLT employing 177 Lu by use of [ 177 Lu]Lu-PSMA-617 has been demonstrated to be effective and well-tolerated, maintaining or even improving quality of life. Other radionuclides such as 161 Tb are currently under investigation concerning clinical feasibility and therapeutic efficacy. However, patient-centered evaluations of well-being and adverse events are scarce. This study evaluates the impact of [ 161 Tb]Tb-PSMA-617 RLT on health-related quality of life (HRQoL) across multiple scales, including adverse events. Methods Analysis included 20 advanced, heavily pre-treated mCRPC patients enrolled in the REALITY registry (NCT04833517) who received [ 161 Tb]Tb-PSMA-617 RLT (median two cycles; mean activity per cycle: 6.1 ± 1.2 GBq) after prior conventional PSMA RLT. HRQoL, covering physical, emotional, cognitive, and social functioning, was assessed using EORTC QLQ-C30. Hematotoxicities, liver and kidney function impairments, as well as xerostomia were evaluated according to CTCAE v5.0. For statistical analysis, the Wilcoxon matched-pairs signed-rank test was employed, with a significance threshold set at p < 0.05. Results Analysis of QLQ-C30 demonstrated that patient-reported well-being was largely maintained. Increased tiredness reached statistical significance ( p = 0.036). Global health ( p = 0.581) and overall quality of life ( p > 0.999) remained stable throughout therapy. Most CTCAE ratings were mild or moderate. Worsening under therapy was limited: One anemia case progressed from CTCAE °2 to °4, and another from °2 to °3. Regarding renal function, two cases progressed from °2 to °3. No cases of xerostomia higher than °2 were observed. Conclusion [ 161 Tb]Tb-PSMA-617 RLT represents a well-tolerated and safe treatment option for advanced mCRPC, with patient-reported quality of life maintained over time, with only rare higher-grade hematological and renal toxicities.