Darolutamide Addition to ADT Delays Metastasis in Very High-Risk Prostate Cancer: Interim Phase 3 Results

The double-blind ARANOTE trial randomized patients receiving radiotherapy plus ADT to darolutamide or placebo. Participants had very high-risk features such as Gleason 9-10, T3b-T4, or node-positive disease. Interim analysis showed longer metastasis-free survival, fewer prostate cancer deaths, and fewer PSA rises with darolutamide. The trial was conducted across six countries by the Australian and New Zealand Urogenital and Prostate Cancer Trials Group with McGill University leadership.

Prior darolutamide data from the ARASENS trial in metastatic hormone-sensitive disease established a survival benefit when combined with docetaxel. This new study targets an earlier, localized population where current standard care still yields 30-40 percent recurrence. Observational patterns indicate that intensified androgen receptor inhibition can delay micrometastatic spread, yet absolute gains depend on baseline risk and radiation dose.

Longer follow-up is required to confirm overall survival and quality-of-life trade-offs. The current evidence comes from an interim analysis of a large randomized trial; such data can support accelerated regulatory review but cannot yet establish definitive practice change without mature endpoints. Next steps include final metastasis-free survival readout and subgroup analyses by radiation field and genomic risk.

Evidence quality is moderate: a well-powered phase 3 RCT with placebo control, but results remain immature and industry-supported. A fully reported trial with verified overall survival benefit at five years would be needed to shift guidelines.