Radiographic Progression Without Prostate-specific Antigen Progression in Metastatic Hormone-sensitive Prostate Cancer: A Retrospective Analysis of the ENZAMET Trial (ANZUP 1304)
- Author(s)
- Inderjeeth, AJ; Martin, AJ; Zielinski, RR; Begbie, S; Cheung, L; Chowdhury, S; Frydenberg, M; Horvath, LG; Joshua, AM; Lawrence, NJ; Marx, G; McCaffrey, J; McDermott, RS; McJannett, M; North, SA; Parnis, F; Parulekar, WR; Pook, DW; Reaume, MN; Sandhu, S; Tan, A; Tan, TH; Thomson, AH; Vera-Badillo, F; Williams, SG; Thomas, H; Yip, S; Zhang, AY; Chi, KN; Stockler, MR; Sweeney, CJ; Davis, ID;
- Journal Title
- European Urology Oncology
- Publication Type
- Feb 2
- Abstract
- BACKGROUND AND OBJECTIVE: ENZAMET randomised 1125 participants with metastatic hormone-sensitive prostate cancer to receive enzalutamide or a standard nonsteroidal antiandrogen (NSAA) combined with testosterone suppression with or without docetaxel. Enzalutamide demonstrated superior progression-free and overall survival (OS). Radiographic progression without prior/concurrent prostate-specific antigen progression (discordant progression; DP) portends poor outcomes. Our aim was to determine the frequency of DP in ENZAMET and the impact of enzalutamide on disease-state transitions. METHODS: A multistate Cox proportional-hazards regression model was used to partition participants into four states: (1) event-free; (2) discordant progression (DP); (3) other types of progression (other progression; OP); and (4) death. KEY FINDINGS AND LIMITATIONS: Enzalutamide prolonged OS in the entire cohort of 1125 participants (hazard ratio [HR] 0.70, 95% confidence interval [CI] 0.58-0.84; p < 0.0001). Radiographic progression occurred in 388/1125 (34%) participants, and DP in 114/1125 (10%), with similar proportions in the enzalutamide arm (55/114, 48%) and NSAA arm (59/114, 52%). Participant characteristics in the DP group were similar between the treatment arms. Enzalutamide delayed DP (HR 0.66, 95% CI 0.46-0.96; p = 0.03) and OP (HR 0.37, 95% CI 0.31-0.44; p < 0.001). The 5-yr OS rate was lower in the DP group (24%) than in the OP group (42%). Among participants whose cancer had not progressed (495/1125), 51/495 (10%) died of non-prostate cancer causes (median follow-up 68 mo). This exploratory analysis is limited by its post hoc nature. CONCLUSIONS AND CLINICAL IMPLICATIONS: DP occurred in 10% of participants and accounted for 30% of progression events observed in ENZAMET. DP was associated with worse OS regardless of treatment. Enzalutamide delayed DP and reduced the risk of DP and OP. Regularly scheduled imaging may be preferable to for-cause imaging in metastatic hormone-sensitive prostate cancer.
- Publisher
- Elsevier
- Keywords
- Anzup; Androgen receptor pathway inhibitor; Discordant progression; Enzamet; Enzalutamide; Hormone-sensitive; Prostate cancer
- Research Division(s)
- Personalised Oncology
- PubMed ID
- 41633909
- Publisher's Version
- https://doi.org/10.1016/j.euo.2026.01.008
- Open Access at Publisher's Site
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Creation Date: 2026-02-09 09:18:22
Last Modified: 2026-02-09 09:23:24