As reported in The Lancet Oncology by Zapatero et al, 10-year results of the Spanish phase III DART 01/05 trial did not support the 5-year findings of significantly improved biochemical disease–free, metastasis-free, and overall survival with long-term vs short-term androgen deprivation plus high-dose radiotherapy in patients with localized prostate cancer. However, clinically relevant improvements in outcomes were observed with long-term vs short-term androgen deprivation in high-risk patients.
Study Details
The open-label multicenter trial included 354 patients with T1c to T3, N0, and M0 adenocarcinoma. They were randomly assigned between November 2005 and December 2010 to receive high-dose radiotherapy (minimum dose = 76 Gy; median dose = 78 Gy) plus 4 months of neoadjuvant and concomitant short-term androgen deprivation (n = 177) or the same treatment followed by 24 months of adjuvant long-term androgen deprivation (n = 177). Patients in the short-term androgen deprivation group received flutamide at 750 mg per day or bicalutamide at 50 mg per day with subcutaneous goserelin 2 months before and 2 months combined with high-dose radiotherapy. Anti-androgen therapy was added during the first 2 months of treatment. Patients receiving long-term androgen deprivation continued to receive goserelin every 3 months for another 24 months.
Key Findings
Median follow-up for the current analysis was 119.4 months (interquartile range = 100.6–124.3 months).
At 10 years:
- Biochemical disease–free survival was 70.2% (95% confidence interval [CI] = 63.1%–77.3%) in the long-term androgen deprivation group vs 62.3% (95% CI = 54.9%–69.7%) in the short-term androgen deprivation group (hazard ratio [HR] = 0.84, 95% CI = 0.50–1.43, P = .52)
- Overall survival was 78.4% (95% CI = 72.1%–84.8%) in the long-term androgen deprivation group vs 73.3% (95% CI = 66.6%–80.0%) in the short-term androgen deprivation group (HR = 0.84, 95% CI = 0.55–1.27, P = .40)
- Metastasis-free survival was 76.0% (95% CI = 69.4%–82.7%) in the long-term androgen deprivation group vs 70.9% (95% CI = 64.0%–77.8%) in the short-term androgen deprivation group (HR = 0.90, 95% CI = 0.37–2.19, P = .81).
At 10 years, among 92 long-term androgen deprivation patients (52%) vs 96 short-term androgen deprivation patients (54%) with high-risk disease:
- Biochemical disease–free survival was 67.2% (95% CI = 57.2%–77.2%) for long-term androgen deprivation vs 53.7% (95% CI = 43.3%–64.1%) for short-term androgen deprivation (HR = 0.90, 95% CI = 0.49–1.64, P = .73)
- Overall survival was 78.5% (95% CI = 69.6%–87.3%) for long-term androgen deprivation vs 67.0% (95% CI = 57.3%–76.7%) for short-term androgen deprivation (HR = 0.58, 95% CI = 0.33–1.01, P = .054)
- Metastasis-free survival was 76.6% (95% CI = 67.6%–85.6%) for long-term androgen deprivation vs 65.0% (95% CI = 55.1%–74.8%) for short-term androgen deprivation (HR = 0.89, 95% CI = 0.33%–2.43%, P = .82).
A total of 11 patients (3%) died from prostate cancer; all were in the high-risk subgroup, including 5 in the long-term androgen deprivation group and 6 in the short-term androgen deprivation group. A total of 76 patients (21%) died from other causes, most commonly second malignancies (n = 31; 9%) and cardiovascular disease (n = 21; 6%). No treatment-related deaths were observed.
The investigators concluded, “After an extended 10-year follow-up, we were unable to support the significant benefit of [long-term androgen deprivation] reported at 5 years. However, the magnitude of the benefit was clinically relevant in high-risk patients. Intermediate-risk patients treated with high-dose radiotherapy do not benefit from [long-term androgen deprivation]. A biological characterization with the inclusion of genomic testing is needed in the decision-making process.”
Almudena Zapatero, PhD, of the Radiation Oncology Department, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria IP, Madrid, is the corresponding author for The Lancet Oncology article.
Disclosure: The study was funded by the Grupo de Investigación en Oncología Radioterápica and Sociedad Española de Oncología Radioterápica, National Health Investigation Fund, and AstraZeneca. For full disclosures of the study authors, visit thelancet.com.
