Adjuvant external beam radiotherapy (EBRT) in the treatment of endometrial cancer: Results of the randomised MRC ASTEC and NCIC CTG EN.5 trial

Abstract

5504 Background: Patients with stage I endometrial cancer at high risk of relapse generally receive adjuvant EBRT following surgery, despite lack of evidence that radiotherapy improves overall survival (OS). ASTEC/EN.5 was designed to investigate whether OS is improved by adjuvant EBRT. An important secondary outcome was pelvic recurrence-free survival. Methods: Patients were randomised to receive immediate EBRT (with linear accelerator delivering 40–46Gy in 20–25 fractions to pelvis) or no EBRT until clinically indicated. Vault brachytherapy (4Gy in 2 fractions (HDR) or 15Gy (LDR)) could be used regardless of EBRT allocation. Centers were required to specify in advance whether brachytherapy would be offered to all patients or to none. The study was powered both to 1) detect a 9–10% absolute improvement in 5-year OS with adjuvant EBRT; and 2) reliably exclude an absolute 5% difference in 5-year OS when combined with other major studies (PORTEC and GOG 99). Results: Between Oct 1996 to Apr 2005, 906 patients (452 EBRT, 454 no EBRT) were randomised internationally. Pre-treatment characteristics were well balanced: median age 66 years; 98% of women WHO PS 0–1; 30% with lymph nodes removed at surgery; 84% endometrioid histology; depth of invasion to endometrium only, inner half and outer half of myometrium 3%, 20% and 77%, respectively; degree of differentiation to grade 1, 2, and 3 26%, 42%, and 31%, respectively. 92% patients in EBRT arm received immediate treatment, 90% receiving all protocol specified treatment. 2% patients in no EBRT arm received immediate EBRT. Brachytherapy was given to 52% patients in both arms. Morbidity was higher in EBRT arm, 56% compared with 24% in no EBRT arm reporting complications of treatment. Grade 3 or higher toxicity was rare. With a median follow-up of 46 months at the time of analysis, 117(13%) have died and 136(17%) have recurred or died. 130 deaths are required to detect a 10% difference in 5-year OS with 5% significance level and 90% power and this will be achieved by April 2007. Conclusions: Compliance was high. Serious complications were rare. The ASTEC/EN.5 trial alone and in combination with PORTEC and GOG99 will answer the question of the benefit of post-operative adjuvant EBRT in patients with endometrial cancer. No significant financial relationships to disclose.