Prognostic Value of Initial Imaging and PSA Change with [(177)Lu]Lu-PSMA-617 Radiopharmaceutical Therapy in Patients with Metastatic Castration-Resistant Prostate Cancer: A ProsTIC Registry Analysis
- Author(s)
- Chen, DC; Buteau, JP; Papa, N; Akhurst, T; Alipour, R; Bollampally, N; Cardin, A; Eifer, M; Casanueva Eliceiry, S; Jackson, P; Jewell, K; Kashyap, R; Kong, G; Kostos, L; Ravi Kumar, A; McIntosh, L; Medhurst, E; Saghebi, J; Sandhu, S; Murphy, DG; Tran, B; Azad, AA; Hofman, MS;
- Journal Title
- Journal of Nuclear Medicine
- Publication Type
- Online publication before print
- Abstract
- [(177)Lu]Lu-PSMA-617 radiopharmaceutical therapy improves survival and quality of life in patients with metastatic castration-resistant prostate cancer. We assessed whether patients who did not achieve an early prostate-specific antigen (PSA) decline after the first cycle (C1) benefited from further [(177)Lu]Lu-PSMA-617. Methods: We analyzed patients with metastatic castration-resistant prostate cancer participating in a registry of [(177)Lu]Lu-PSMA-617 (ProsTIC registry, NCT04769817). Patients with a PSA either rising (≥25% increase from baseline) or stable (30% decrease to 25% increase from baseline) within 28 d of starting treatment (C1) and consequently received a second dose (cycle 2) were included. Biochemical response was defined as a PSA decline of more than 50% from baseline (PSA-50) within 20 wk after C1. Quality of life was assessed on 2 validated scales. We evaluated the effect of PSA change and 3 imaging parameters (pretreatment PSMA PET SUV(mean), pretreatment [(18)F]FDG PET metabolic tumor volume, and mean total tumor dosimetry on SPECT/CT after C1) with these outcomes and survival time after cycle 2. Results: Of 195 patients, 103 met inclusion criteria between January 5, 2021, and March 30, 2023, with an early PSA rise in 31 patients (30%) or stable PSA in 72 patients (70%). Of 103 patients, 45 (44%) achieved PSA-50 by 140 d after C1. Seven of 31 patients (23%) and 38 of 72 patients (53%) with early rising and stable PSA, respectively, had achieved a PSA-50 by 140 d after C1. A PSMA SUV(mean) of 10 or more versus an SUV(mean) of less than 10 conferred a higher chance of PSA-50 (59% vs. 37%; odds ratio, 2.53; 95% CI, 1.08-5.95). In total, 59 deaths were recorded with a median overall survival of 11.3 mo after cycle 2. [(18)F]FDG metabolic tumor volume was the only variable to have a meaningful association with overall survival. Patients with baseline pain scores of 10 or greater according to EORTC QLQ-C30 pain or 2 or greater according to BPI-SF had clinically meaningful reductions in pain in 39 of 55 patients (71%) and 17 of 37 patients (46%), respectively. Conclusion: Discontinuing [(177)Lu]Lu-PSMA-617 based solely on PSA response after just 1 cycle is not advisable as a substantial number of patients achieve PSA-50 or a reduction in pain. Baseline imaging parameters have prognostic utility and can assist in patient counseling and clinical decision-making.
- Keywords
- Psma; prostate-specific membrane antigen; radiopharmaceutical therapy; theranostics
- Department(s)
- Cancer Imaging; Surgical Oncology; Medical Oncology
- Publisher's Version
- https://doi.org/10.2967/jnumed.125.270804
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2025-11-06 11:44:59
Last Modified: 2025-11-06 11:45:06