Long-term androgen deprivation therapy (ADT) does not provide a significant benefit over short-term ADT in patients with localized prostate cancer receiving high-dose radiotherapy (RT), according to 10-year results from the DART 01/05 trial published in The Lancet Oncology.1
Researchers found no significant differences in survival outcomes with long-term or short-term ADT in the overall cohort or when patients were analyzed by risk group.
However, the researchers said there was a “clinically relevant” benefit of long-term ADT in patients with high-risk disease. In fact, the researchers concluded that the results support long-term ADT and high-dose RT as standard care for high-risk patients.
The phase 3 DART 01/05 trial (ClinicalTrials.gov Identifier: NCT02175212) was designed to compare short-term ADT (4 months) with long-term ADT (28 months) in patients with intermediate- and high-risk prostate cancer treated with high-dose RT (minimum dose, 76 Gy).
The 5-year results from DART 01/05 showed that long-term ADT significantly improved biochemical disease-free survival (DFS), metastasis-free survival (MFS), and overall survival (OS).2 However, results differed at the 10-year mark.1
The 10-year analysis included 354 patients — 177 who received short-term ADT and 177 who received long-term ADT. The median follow-up was 119.4 months.
In the overall cohort, the 10-year biochemical DFS rate was 70.2% with long-term ADT and 62.3% with short-term ADT (hazard ratio [HR], 0.84; 95% CI, 0.50–1.43; P =.52). For the high-risk patients, the DFS rates were 67.2% and 53.7%, respectively (HR, 0.90; 95% CI, 0.49–1.64; P =.73). For intermediate-risk patients, the DFS rates were 73.5% and 72.6%, respectively (HR, 0.72; 95% CI, 0.26–2.06; P =.54).
The 10-year MFS rates in the overall cohort were 76.0% with long-term ADT and 70.9% with short-term ADT (HR, 0.90; 95% CI, 0.37–2.19; P =.81). For the high-risk cohort, the MFS rates were 76.6% and 65.0%, respectively (HR, 0.89; 95% CI, 0.33–2.43; P =.82). For the intermediate-risk cohort, the MFS rates were 75.4% and 77.8%, respectively (HR, 1.03; 95% CI, 0.15–6.94; P =.98).
In the overall cohort, the 10-year OS rate was 78.4% with long-term ADT and 73.3% with short-term ADT (HR, 0.84; 95% CI, 0.55–1.27; P =.40). In the high-risk cohort, the OS rates were 78.5% and 67.0%, respectively (HR, 0.58; 95% CI, 0.33–1.01; P =.054). In the intermediate-risk cohort, the OS rates were 78.5% and 80.6%, respectively (HR, 1.35; 95% CI, 0.70–2.58; P =.37).
The researchers theorized that the differences between the 5-year results and the 10-year results may be due, in part, to patients’ age at baseline. The median age at diagnosis was 72 years in the short-term ADT group and 71 years in the long-term ADT group. The competing risk of non-prostate cancer death in an aging population with a high life expectancy may have led to the current findings, according to the researchers.
Disclosures: This research was supported by AstraZeneca, the National Health Investigation Fund, and Grupo de Investigación en Oncología Radioterápica and Sociedad Española de Oncología Radioterápica. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
1. Zapatero A, Guerrero A, Maldonado X, et al. High-dose radiotherapy and risk-adapted androgen deprivation in localised prostate cancer (DART 01/05): 10-year results of a phase 3 randomised, controlled trial. Lancet Oncol. Published online April 12, 2022. https://doi.org/10.1016/S1470-2045(22)00190-5
2. Zapatero A, Guerrero A, Maldonado X, et al. High-dose radiotherapy with short-term or long-term androgen deprivation in localised prostate cancer (DART01/05 GICOR): A randomised, controlled, phase 3 trial. Lancet Oncol. 2015;16: 320–27. doi:10.1016/S1470-2045(15)70045-8