Short-term Androgen Deprivation Therapy and High-dose Radiotherapy in Intermediate- and High-risk Localized Prostate Cancer: Results from the GETUG 14 Randomized Phase 3 Trial

Abstract

Background and objective: Few studies have compared short-term androgen deprivation (STADT) combined with high-dose radiotherapy (STADT-RT) versus high-dose radiotherapy (RT) alone in localized prostate cancer. Methods: The GETUG 14 study randomized 376 patients to RT (n = 191) or STADT-RT (n = 179). The RT dose was 80 Gy in both arms. STADT consisted of monthly triptorelin and daily flutamide for a total duration of 4 mo, starting 2 mo before RT. Disease-free survival (DFS) was the primary endpoint. Secondary endpoints were overall survival (OS), biochemical failure (BF), metastasis failure (MF), toxicity, and quality of life. Key findings and limitations: Among the 370 patients in the modified intention-to-treat population, 241 (65%) had intermediate-risk and 107 (28%) high-risk prostate cancer. At median follow-up among surviving patients of 84 mo (interquartile range 62–99 mo), the 5-yr DFS rate was 76% in RT arm versus 84% in STADT-RT arm (hazard ratio [HR] 0.64, 95% confidence interval [CI] 0.43–0.94]). ADT addition decreased BF (HR 0.45, 95% CI 0.28–0.72) and MF (HR 0.5, 95% CI 0.23–1.11) but not OS (HR 1.22, 95% CI 0.65–2.29). There were no significant differences for RT versus STADT-RT in the incidence rates for grade ≥2 toxicity in terms of acute gastrointestinal (GI) toxicity (26%, 95% CI 20–32 vs 26%, 95% CI 20–33), acute genitourinary (GU) toxicity (39%, 95% CI 32–46% vs 42%, 95% CI 35–50%), late GI toxicity (21%, 95% CI 16–28% vs 23%, 95% CI 18–30%), or late GU toxicity (30%, 95% CI 24–38% vs 27%, 95% CI 21–34%). Conclusions and clinical implications: STADT is a well-tolerated and effective strategy that can enhance oncological outcomes when combined with high-dose RT, particularly for patients with intermediate- or high-risk prostate cancer.