Does short-term androgen depletion add to high dose radiotherapy (80 Gy) in localized intermediate risk prostate cancer? Final analysis of GETUG 14 randomized trial (EU-20503/NCT00104741).

5021 Background: Multi-center randomized trial to evaluate the addition of 4-month androgen deprivation to high dose radiotherapy in intermediate risk localized prostate adenocarcinoma patients (pts). Methods: eligible pts were randomly assigned to high dose conformal radiotherapy (prostate 80 Gy / 40 fractions; seminal vesicles 46 Gy / 23 fractions) either alone (group RT) or in combination with 4-month androgen deprivation (flutamide + triptorelin starting 2 months before radiotherapy, group AD-RT). Lymphadenectomy was mandatory when the risk of node involvement was > 10% (Partin). The primary endpoint was survival without clinical / biochemical relapse at 5 years. Secondary endpoints included overall survival, toxicity (CTCAE v3) and quality of life (QLQ-C30, PR-25). The a-priori sample size was 450 patients, 225 per arm (0.90 power to detect an increase from 75 to 85%, bilateral α = 0.05). Results: 377 pts were included between September 2003 and June 2010. The inclusions were prematurely closed, due to slow accrual. Intent-to-treat analysis was made for 370 pts (191 RT, 179 AD-RT). Prognostic factors were well balanced between the two arms. The median follow-up duration was 84 months (range: 3 to 132). At 5 years, the probabilities of survival without clinical / biochemical relapse were 76% [95% CI: 69% – 81%] and 84% [78% – 89%] in RT and AD-RT groups, respectively (p = 0.02). Overall survival probabilities were 94% [90% - 97%] and 93% [88% - 96%] respectively (p = 0.54).Cumulative incidence of biochemical failure were 21% [15% – 26%] and 10% [6% – 15%], respectively (p < 0.01). The probabilities of being free of grade 3-4 toxicities were 96% and 95% (p = 0.69) for digestive tract, 93% and 95% (p = 0.44) for urinary tract. Conclusions: 4 months of androgen blockade improves event-free survival at 5 years in pts with intermediate risk prostate adenocarcinoma when treated with high dose radiotherapy. Longer follow-up is required to demonstrate an impact on overall survival. Clinical trial information: EU-20503 / NCT00104741.