Prognostic Value of Interim PSMA-PET Total Tumor Volume for Overall Survival Within ENZA-p, A Randomized Phase 2 Trial of Enzalutamide Versus Enzalutamide Plus [(177)Lu] Lu-PSMA-617 (ANZUP1901)
- Author(s)
- Emmett, L; Papa, N; Sartor, O; Morris, MJ; Subramaniam, S; Crumbaker, M; Ayati, N; Chen, J; Herrmann, K; Gafita, A; Swiha, M; Joshua, AM; Weickhardt, A; Lee, ST; Ng, S; Francis, RJ; Goh, JC; Pattison, DA; Ho, B; Khan, S; Tan, TH; Bills, M; Nguyen, A; Thein, T; Sidhom, G; Wong, K; Martin, AJ; Hofman, MS; Sandhu, S; Thomas, H; Stockler, MR; Davis, ID; ENZA-p Trial Investigators; Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP);
- Journal Title
- European Urology
- Publication Type
- Online publication before print
- Abstract
- BACKGROUND AND OBJECTIVE: Interim [(68)Ga]Ga-prostate-specific membrane-antigen positron emission tomography/computed tomography (PSMA-PET/CT) has prognostic potential for overall survival (OS) in metastatic castrate-resistant prostate cancer (mCRPC), although evidence is limited. This ENZA-p sub-study evaluated 3-mo PSMA-total-tumor-volume (PSMA-TTV) as a prognostic biomarker for OS with enzalutamide ± [(177)Lu]Lu-PSMA-617. DESIGN, SETTING AND PARTICIPANTS: ENZA-p is a randomized, phase 2 trial. Participants with mCRPC and risk factors for early treatment failure with enzalutamide were randomized (1:1) to enzalutamide or enzalutamide + [(177)Lu]Lu-PSMA-617. Participants underwent baseline and 3-mo [(68)Ga]Ga-PSMA-11-PET/CT, quantified to derive PSMA-TTV. We evaluated the prognostic value of PSMA-TTV change, and residual PSMA-TTV at 3-mo for OS (NCT04419402). RESULTS AND LIMITATIONS: This sub-study included 152/162 (94%) randomized participants with a 3-mo PSMA-PET. Median OS was 27 mo (95% confidence interval [CI] 23-30). Baseline median PSMA-TTV 230 ml (interquartile range [IQR] 75-635) and 3-mo PSMA-TTV 103 ml (IQR 24-457). The median change in PSMA-TTV from baseline was -34% (IQR -76% to 16%) with 50/152 (33%) participants with increase in PSMA-TTV. Any increase versus decrease in PSMA-TTV at 3-mo was associated with shorter OS (HR 2.52, 95% CI 1.65-3.85) and decreased 2-yr survival 30% (95% CI 17-43) versus 67% (95% CI 56-75) (log-rank p < 0.0001). Residual 3-mo PSMA-TTV higher versus lower than the median (103 ml) was associated with shorter OS (HR 3.76, 95% CI 2.39-5.92) and lower 2-yr survival 34% (95% CI 23-45) versus 76% (95% CI 64-84) (log-rank p < 0.0001). This association was independent of treatment arm and prostate-specific antigen (PSA) response. CONCLUSIONS: PSMA-TTV at 3 mos was prognostic for OS independent of study treatment and PSA response in ENZA-p, warranting further prospective validation of interim PSMA-PET response criteria.
- Keywords
- (177)LuPSMA-617; Enzalutamide; Interim response; Metastatic prostate cancer; Psma-pet; Total tumor volume
- Department(s)
- Cancer Imaging; Medical Oncology
- Publisher's Version
- https://doi.org/10.1016/j.eururo.2026.03.026
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2026-04-28 02:39:56
Last Modified: 2026-04-28 02:40:14