Clinical Summary: 

• Design/Population: The DASL-HiCaP trial evaluated darolutamide plus androgen deprivation therapy (ADT) and radiotherapy versus placebo plus ADT and radiotherapy in patients with very high-risk localized or biochemically persistent/recurrent prostate cancer within 1 year of radical prostatectomy.
• Key Outcomes: Adding darolutamide significantly improved metastasis-free survival, reducing the risk of metastasis or death by 58% compared with placebo. Prostate-specific antigen progression-free survival also favored darolutamide, while overall survival data remained immature.
• Clinical Relevance: These findings support darolutamide-based treatment intensification for patients with very high-risk localized or biochemically persistent/recurrent prostate cancer receiving ADT and radiotherapy. Continued follow-up is needed to determine whether the metastasis-free survival benefit translates into improved overall survival. 

Results from the DASL-HiCaP trial demonstrated that adding darolutamide to androgen deprivation therapy (ADT) and radiotherapy significantly improved metastasis-free survival in patients with very high-risk localized or biochemically persistent/recurrent prostate cancer, supporting treatment intensification in this population.

These findings were presented by Tamim Niazi, MD, McGill University, Montreal, Canada, during a Presidential Symposium at the European Society for Medical Oncology (ESMO) Congress.

In this trial, researchers enrolled 1106 patients with very high-risk prostate cancer, including those with persistent or recurrent disease, within 1 year of radical prostatectomy. Patients were randomized 1:1 to receive 600 mg of darolutamide twice daily (n = 553) or placebo (n = 553) for 96 weeks, in combination with a luteinizing hormone-releasing hormone analog for 96 weeks and radiotherapy to the prostate or prostate bed and pelvic lymph nodes. 

The primary end point was metastasis-free survival, assessed using conventional imaging, including CT and/or technetium bone scans. Secondary end points included prostate-specific antigen progression-free survival (PSA-PFS), prostate cancer-specific survival, overall survival (OS), and safety. 

At a median follow-up of 3.8 years, the 4-year metastasis-free survival rate was 95% in the darolutamide arm and 88% in the placebo arm, corresponding to a 58% reduction in the risk of metastasis or death (hazard ratio [HR], 0.42; 95% confidence interval [CI], 0.27 to 0.66; P = .0001). Metastasis-free survival events occurred in 27 patients receiving darolutamide and 63 patients receiving placebo.

At 4 years, the PSA-PFS rate was 91% in the darolutamide arm and 83% in the placebo arm. PSA progression events occurred in 46 patients receiving darolutamide and 95 patients receiving placebo. The 4 years prostate cancer-specific survival rate was 99% in both treatment arms, with 4 events in the darolutamide arm and 7 events in the placebo arm.

The 4-year OS rates were 97% and 95%, respectively. Overall, 21 deaths occurred in the darolutamide arm compared with 24 in the placebo arm. Although the findings demonstrated a significant metastasis-free survival benefit, an OS advantage has not been established. Follow-up remains ongoing to assess longer-term survival outcomes.

Grade ≥3 adverse events were reported in 43% of patients in the darolutamide arm and 36% of patients in the placebo arm. Grade ≥2 adverse events of special interest included fatigue or asthenia (14% vs 10%), hypertension (7% vs 9%), fractures (2% vs 3%), and cardiac events (3% vs 3%). 

Source:

Niazi T, et al. Darolutamide with androgen deprivation therapy (ADT) and definitive or salvage locoregional radiation therapy (RT) for localised, very high-risk prostate cancer: Interim analysis of an international, placebo-controlled, randomised phase 3 trial (DASL-HiCaP; ANZUP1801). Presented at ESMO Congress. October 23-27, 2026; Madrid, Spain. LBA4.