Phase III Trial Shows Improved Survival With Long‑Term Androgen-Deprivation Therapy Plus High-Dose Radiotherapy in Localized Prostate Cancer
In the Spanish phase III DART01/05 GICOR trial reported in Lancet Oncology, Zapatero and colleagues found that long-term androgen-deprivation therapy (ADT) increased biochemical disease-free survival and overall survival vs short-term ADT when combined with high-dose radiotherapy in men with localized prostate cancer.
Study Details
In this open-label trial, 355 patients were randomly assigned between November 2005 and December 2010 to receive 4 months of ADT (n = 178) or 24 months of ADT (n = 177) following three-dimensional conformal radiotherapy at a minimum dose of 76 Gy (range, 76–82 Gy). Patients had to have clinical stage T1c–T3b, N0, M0 prostate adenocarcinoma with intermediate or high risk based on 2005 National Comprehensive Cancer Network criteria.
The short-term ADT group received 4 months of neoadjuvant and concomitant androgen deprivation with subcutaenous goserelin (Zoladex) 2 months before and 2 months in combination with high-dose radiotherapy, with flutamide at 750 mg/d or bicalutamide at 50 mg/d added during the first 2 months of treatment. Patients in the long-term ADT group continued with the same luteinizing hormone–releasing hormone analog every 3 months for 24 months. The primary endpoint was biochemical disease-free survival on intention-to-treat analysis.
Increased Survival
After a median follow-up of 63 months, the 5-year biochemical disease-free survival rate was 90% in the long-term ADT group vs 81% in the short-term ADT group (hazard ratio [HR] = 1.88, P = .01). The 5-year overall survival rate was 95% vs 86% (HR = 2.48, P = .009), and the 5-year metastasis-free survival rate was 94% vs 83% (HR = 2.31, P = .01).
Benefits of long-term ADT were more pronounced in high-risk patients. Five-year rates were 88% vs 76% (HR = 1.91, P = .054) for biochemical disease-free survival, 96% vs 82% (HR = 3.43, P = .015) for overall survival, and 94% vs 79% (HR = 2.27, P = .041) for metastasis-free survival among high-risk patients.
Among intermediate-risk patients, 5-year rates were 92% vs 88% (HR = 1.82, P = .174) for biochemical disease-free survival, 94% vs 91% (HR = 1.67, P = .318) for overall survival, and 94% vs 89% (HR = 2.14, P = .124) for metastasis-free survival.
Late Toxicity
Grade 3 late rectal toxicity occurred in 2% vs 1% of patients, and grade 3 or 4 late urinary toxicity occurred in 3% vs 3%. No treatment-related deaths were reported.
The investigators concluded: “Compared with short-term androgen deprivation, 2 years of adjuvant androgen deprivation combined with high-dose radiotherapy improved biochemical control and overall survival in patients with prostate cancer, particularly those with high-risk disease, with no increase in late radiation toxicity. Longer follow-up is needed to determine whether men with intermediate-risk disease benefit from more than 4 months of androgen deprivation.”
Almudena Zapatero, PhD, of Hospital Universitario de la Princesa, Madrid, is the corresponding author for the Lancet Oncology article.
The study was funded by the Spanish National Health Investigation Fund and AstraZeneca. For full disclosures of the study authors, visit www.thelancet.com.
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