Combining short-term androgen deprivation therapy (ADT) with high-dose radiotherapy improves disease-free survival (DFS) in patients with localized prostate cancer, according to the GETUG 14 trial presented at the 2024 ASTRO Annual Meeting. The study, a phase 3 randomized trial, found that the addition of ADT to high-dose radiotherapy prolonged DFS and reduced biochemical failure, marking a significant advancement in treating intermediate- and high-risk localized prostate cancer.
GETUG 14 Trial Details
The GETUG 14 trial (NCT00104741) enrolled 376 patients with localized prostate cancer, randomizing them to either high-dose radiotherapy alone (n=191) or short-term ADT plus high-dose radiotherapy (n=179). Both arms received a radiotherapy dose of 80 Gy. The ADT regimen consisted of monthly triptorelin and daily flutamide for 4 months, initiated 2 months before radiotherapy. The primary endpoint was disease-free survival, with secondary endpoints including overall survival, biochemical failure, metastasis failure, toxicity, and patient-reported quality of life.
Key Findings
After a median follow-up of 84 months, the 5-year DFS rate was 84% in the ADT-radiotherapy arm compared to 76% in the radiotherapy-alone arm (HR, 0.64; 95% CI, 0.43-0.94; P = .02). Specifically, among patients with intermediate-risk disease, the 5-year DFS rate was 87% in the ADT-radiotherapy arm and 74% in the radiotherapy-alone arm (HR, 0.55; 95% CI, 0.33-0.90; P = .02). However, for high-risk disease, the 5-year DFS rates were 79% and 75%, respectively (HR, 0.76; 95% CI, 0.40-1.47; P = .40), indicating no significant difference in this subgroup.
The rate of biochemical failure at 5 years was significantly lower in the ADT-radiotherapy arm (10%) compared to the radiotherapy-alone arm (21%), with an HR of 0.45 (95% CI, 0.28-0.72; P = .001). However, the trial did not find a significant difference between the two arms regarding metastasis failure or overall survival.
Toxicity Profile
Regarding toxicity, the study reported no significant differences between the ADT-radiotherapy arm and the radiotherapy-alone arm in grade 2 or higher early/late genitourinary toxicities, early/late gastrointestinal toxicities, or late erectile dysfunction. Specifically:
- Grade 2 or higher early genitourinary toxicities: 42% (ADT-radiotherapy) vs 39% (radiotherapy-alone)
- Grade 2 or higher late genitourinary toxicities: 27% vs 30%
- Grade 2 or higher early gastrointestinal toxicities: 26% in both arms
- Grade 2 or higher late gastrointestinal toxicities: 23% vs 21%
- Grade 2 or higher late erectile dysfunction: 63% vs 61%
Notably, the rate of grade 2 or higher early erectile dysfunction was significantly higher in the ADT-radiotherapy arm (31%) compared to the radiotherapy-alone arm (6%; P < .001).
Expert Commentary
Dr. Nicolas Demogeot, MD, of Institut de Cancerologie de Lorraine, stated, "Short-term ADT improves disease-free survival in intermediate- and high-risk prostate cancer patients receiving high-dose radiotherapy without increasing gastrointestinal and genitourinary toxicities." He emphasized that high-dose radiotherapy should be combined with short-term ADT to enhance outcomes in intermediate- and high-risk localized prostate cancer.
