ADDING darolutamide to hormone therapy and radiotherapy significantly improved metastasis-free survival in patients with very high-risk prostate cancer, according to Phase III results presented at the European Society for Medical Oncology (ESMO) Congress 2026.
In the DASL-HiCaP trial, the addition of darolutamide reduced the risk of metastasis or death by 58% compared with placebo. The findings come from a planned interim analysis of an international, randomised study involving 1,106 patients.
Prostate cancer is the second most common cancer among men worldwide, with an estimated 1.5 million new cases and 420,000 deaths in 2024. For patients with very high-risk disease, preventing the cancer from spreading remains an important treatment goal.
The trial was designed to establish whether adding darolutamide to androgen deprivation therapy (ADT) and radiotherapy could improve outcomes for patients with very high-risk localised prostate cancer, or cancer that persisted or recurred biochemically after prostate removal.
Very high-risk prostate cancer can spread despite treatment, making better ways to prevent metastasis an important research priority. In DASL-HiCaP, 73% of patients had a Gleason score of 9–10, and 29% had pelvic lymph node involvement visible on CT.
Participants received an LHRH analogue, a form of ADT, for 96 weeks alongside radiotherapy to the prostate or prostate bed and pelvic lymph nodes. They were then randomly assigned to receive either darolutamide 600 mg or placebo twice daily for 96 weeks.
Some participants had localised disease, while others had persistent or recurrent disease indicated by prostate-specific antigen (PSA) levels within 1 year of radical prostatectomy. Overall, 15% had undergone previous prostatectomy.
The primary endpoint for the trial was metastasis-free survival assessed using conventional imaging, including CT and/or bone scans.
Secondary endpoints included PSA progression-free survival, prostate cancer-specific survival, and overall survival.
After a median follow-up of 3.8 years, estimated 4-year metastasis-free survival was 95% in the darolutamide group versus 88% in the placebo group.
During follow-up, 27 patients receiving darolutamide developed metastases or died, compared with 63 receiving placebo. Overall, darolutamide reduced the risk of metastasis or death by 58% (HR: 0.42; 95% CI: 0.27–0.66; p=0.0001).
PSA progression-free survival also favoured darolutamide. At 4 years, estimated rates were 91% versus 83% for the placebo group, with a hazard ratio of 0.47 (95% CI: 0.33–0.67).
Overall survival results do still remain uncertain, however. At the interim analysis, there had been 21 deaths in the darolutamide group and 24 in the placebo group (HR: 0.88; 95% CI: 0.49–1.59).
In terms of safety and tolerability, grade 3 or higher adverse events occurred in 43% of patients receiving darolutamide and 36% receiving placebo.
Fatigue or asthenia of Grade 2 or higher occurred in 14% versus 10%, while corresponding rates of hypertension were 7% versus 9% in respective groups.
The investigators concluded that adding darolutamide significantly improved metastasis-free survival and are “excited” about the results.
In a press conference at the ESMO Congress 2026, Professor Tamin Niazi, lead author of the trial, said that the new therapy combination could “redefine the paradigm of care for patients with prostate cancer with high risk of recurrence”.
The findings add to a changing treatment landscape in which radiotherapy is increasingly combined with intensified hormone therapy for selected patients with high-risk disease.
Follow-up is ongoing to establish whether the improvement translates into an overall survival benefit.
Reference
Niazi T et al. Darolutamide with androgen deprivation therapy and definitive or salvage locoregional radiation therapy for localised, very high-risk prostate cancer: Interim analysis of an international, placebo-controlled, randomised phase 3 trial. Abstract LBA4. ESMO Congress 2026. Clinical trial: NCT04136353. ESMO Congress, 23-27 October 2026.
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