ENZARAD (ANZUP 1303): Phase 3 Trial of Enzalutamide With Androgen Deprivation Therapy and Radiation Therapy in High-Risk Localized or Locally Advanced Prostate Cancer
In brief
Enzalutamide did not significantly improve metastasis-free survival at 8 years (74% vs 72%)
Among 802 participants receiving prostate radiation and 2 years of androgen deprivation therapy, adding enzalutamide did not significantly improve 8-year metastasis-free survival compared with an older antiandrogen: rates were 74% versus 72%. A prespecified subgroup receiving pelvic lymph node radiation showed a possible benefit, but the overall result was null, leaving that subgroup finding to be clarified.
- Journal
- Journal of clinical oncology : official journal of the American Society of Clinical Oncology (Q1)
- Published
- 24 October 2026
- Study design
- Non-randomized / quasi-experimental trial
- Evidence level
- Level 2, Moderate (CEBM 2b)
- Authors
- Williams S, Sweeney CJ, Thomas H, Mak B, Zhang A, Lim TS, et al.
- PMID
- 42921729
- DOI
- 10.1200/JCO-26-01794
Why clinicians should know about it
- Picked for Radiation Oncology (paper of the day, 29 October 2026): Phase III trial directly tests systemic intensification with definitive radiotherapy
Abstract
BACKGROUND: The effects of adding enzalutamide to androgen deprivation therapy (ADT) and radiotherapy for high-risk localized or locally advanced prostate cancer were unknown. METHODS: Open-label, phase 3 trial of definitive prostate radiotherapy with 24 months of ADT and 1:1 randomization to either enzalutamide (160mg daily for 24 months) or an older nonsteroidal antiandrogen (NSAA) for 6 months. The primary endpoint was metastasis-free survival on conventional imaging (MFS-CI) with computerized tomography and/or 99mTc-bone scintigraphy. Radiation to pelvic lymph nodes was required for cN1 disease but optional for cN0. RESULTS: 802 participants were randomized. After a median follow-up of 92 months, 207 MFS-CI events were reported (98 enzalutamide, 109 NSAA) with 8-year MFS-CI rates 74% vs 72%, hazard ratio [HR] 0.88, 95% confidence interval [CI], 0.67 to 1.15; P=0.34). Prespecified subgroup analyses noted enzalutamide was associated with a possible MFS-CI benefit in the subgroup undergoing planned pelvic nodal radiotherapy, N=324 (HR 0.47, 95% CI: 0.29 to 0.76 Padjusted =0.004). Grade 3-5 adverse events were reported in 185 participants in each arm. CONCLUSIONS: The use of enzalutamide rather than NSAA in addition to radiotherapy and ADT for 2 years showed no significant MFS-CI or OS improvement at 8 years.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.