Sunita Somvanshi
Darolutamide DASL-HiCaP Trial Cuts Prostate Cancer Metastasis Risk by 58%, Phase 3 Data Shows
Men with high-risk localized prostate cancer facing radiotherapy now have concrete new phase 3 data to raise with their oncology team. Results from the DASL-HiCaP trial, presented at the ESMO 2026 Presidential Symposium on 24 October, show that adding darolutamide to standard hormone therapy and radiation cut the risk of cancer spreading or death by more than half.
The trial enrolled 1,106 participants across Australia, New Zealand, the UK, the US, Canada, and Ireland, coordinated through the ANZUP Clinical Trials Group (ANZUP1801 / NCT04136353) with Bayer. It compared darolutamide plus androgen deprivation therapy (ADT) and radiation against placebo plus ADT and radiation. The headline result: a 58% reduction in the risk of metastasis or death (hazard ratio 0.42; 95% CI: 0.27–0.66; p=0.0001). Four-year metastasis-free survival was 95% with darolutamide compared with 88% on placebo.
Patients currently undergoing definitive or salvage radiotherapy for high-risk localized prostate cancer now have phase 3 evidence to reference with their specialist. Darolutamide is not yet approved for this localized disease setting — regulatory submissions will follow the completed trial analysis — but the data provides clear justification to ask about trial access or how upcoming guideline changes might apply to your treatment plan.
What the Trial Found
PSA progression-free survival backed up the headline figure: a 53% risk reduction (hazard ratio 0.47). Grade 3 or higher adverse events occurred in 43% of the darolutamide group versus 36% with placebo. Fatigue and hypertension were among the grade 2 or higher special-interest events recorded. The trial covered two patient populations: those with high-risk localized prostate cancer receiving definitive radiotherapy, and those with biochemically recurrent disease after radical prostatectomy receiving salvage radiotherapy.
Darolutamide (brand name Nubeqa) is already approved in more than 85 markets for metastatic hormone-sensitive prostate cancer and non-metastatic castration-resistant prostate cancer. It is not approved by any regulator — including the FDA, EMA, MHRA, or TGA — for early, localized high-risk disease. Regulatory applications are expected once the full trial analysis is complete.
The 4-year metastasis-free survival result of 95% versus 88% is the primary endpoint and the figure that will underpin regulatory submissions. The overall survival hazard ratio at this interim analysis — HR 0.88 (95% CI: 0.49–1.59), comparing 97% survival with darolutamide against 95% with placebo — is not statistically significant. That is not a failure of the drug; it reflects the biology of high-risk localized prostate cancer, which takes years for mortality differences to become statistically detectable. Overall survival data is continuing to follow up.
Is darolutamide approved for localized prostate cancer?
No. Darolutamide (Nubeqa) is approved in more than 85 markets for metastatic hormone-sensitive prostate cancer and non-metastatic castration-resistant prostate cancer. It has not been cleared by any regulator for early, localized high-risk disease. Regulatory submissions to the FDA, EMA, MHRA, and TGA are expected to follow the completed DASL-HiCaP analysis.
Patients with high-risk localized prostate cancer should ask their oncologist about the DASL-HiCaP data ahead of any treatment planning discussion.
