ASTEC/EN.5.

Methods	Two multicentre randomised trials combined data From July 1996 to March 2005, ASTEC recruited participants from UK, Poland, Norway and New Zealand; EN.5 recruited participants from Canada, Australia and USA. Randomisation was computer‐generated with central allocation via telephone.
Participants	789 ASTEC participants and 116 EN.5 participants with histologically confirmed intermediate‐risk (stage IA and IB Grade 3, IC and IIA Grade 1 and 2) or high‐risk (IC and IIA Grade 3, and IIB) early‐stage endometrial cancer. Lymphadenectomy was not required. Women with positive lymph nodes were eligible for ASTEC but not EN.5. Randomisation was based on the local pathology report. VBT was allowed if the centre's policy was to offer it to all stage I and IIa women, irrespective of group allocation.
Interventions	EBRT (40‐46 Gy in 20‐25 daily fractions) versus no additional treatment until recurrence (NAT), with or without VBT.
Outcomes	Primary outcome was overall survival. Secondary outcomes were disease‐specific survival, disease‐specific recurrence, recurrence‐free survival, isolated loco‐regional recurrence, and treatment toxicity. Median follow‐up was 58 months.
Notes	Overall, group size (452 EBRT and 453 NAT) and baseline characteristics were similar, except for small imbalance in proportion of high‐risk women (25% in NAT versus 20% in ERBT group). 52% in NAT group and 54% in EBRT group received VBT. 5% of ASTEC women received other adjuvant treatment, balanced between groups. 92% in the EBRT group received the allocated treatment; 2% in the observation group received EBRT. Analysis was by ITT.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Computer‐generated randomisation.
Allocation concealment (selection bias)	Low risk	Central allocation via telephone.
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Assessment of cause of death was made by the chief investigator blinded to the treatment group (ASTEC) and was classified as treatment‐related, disease‐related treatment and disease‐related, or other (non‐endometrial cancer, non‐treatment‐related). Participants and other personnel were not blinded.
Incomplete outcome data (attrition bias) All outcomes	Low risk	Low level of missing data since all assessed for primary outcome.
Selective reporting (reporting bias)	Low risk	All expected pre‐specified outcomes reported. Analysis by ITT.
Other bias	Low risk	Baseline data were generally balanced between the two groups, except for a small imbalance in the proportion of high‐risk women, with 25% of those in the observation group classified as high risk compared with 20% in the external beam radiotherapy group.