PORTEC-4a: Randomised trial of standard or molecular profile-based recommendation for radiotherapy after surgery for women with early stage endometrial cancer

INTERVENTION: Participants are randomly allocated to one of two arms: 1. Standard arm: Vaginal brachytherapy (3 short outpatient internal radiation treatments over 2 weeks to the vaginal cuff), based on PORTEC‐2 trial. 2. Investigational arm: Based on the molecular profile, either no further treatment after surgery (for favourable profile), or vaginal brachytherapy (as above, for intermediate profile) or external beam radiation therapy (5 weeks of daily out‐patient external radiation treatments to the pelvic area, for unfavourable profile). After completion of patient recruitment, follow‐up will continue until the time of final analysis is reached and until at least 5 years after inclusion of each patient. CONDITION: Endometrial cancer ; Cancer PRIMARY OUTCOME: Vaginal recurrence, measured during each follow‐up visit by vaginal inspection and pelvic examinations (3 monthly first 2 years, 6 monthly until 5th year) and confirmation by histology in case of suspected recurrence; SECONDARY OUTCOME: 1. Recurrence‐free survival ‐ regular follow‐up visits (3 monthly first 2 years, 6 monthly until 5th year) with history focused on symptoms and side effects and pelvic examination; further evaluation in case of suspected recurrence locally or at distant sites by (PET)‐CT and/or MRi scanning and histological confirmation. In case of death, information on date and cause of death are recorded; 2. 5‐year vaginal control ‐ local recurrence free at 5 years either without any evidence of recurrence or after treatment for vaginal recurrence; 3. Quality of life‐ Patients receive a QoL questionnaire consisting of EORTC QLQ‐C30 and EN24 at baseline (after surgery, before study treatment or observation), at 6 weeks after randomisation, and at 6, 12, 18, 24, 36 and 60 months after randomisation; 4. Side effects‐ Regular follow‐up visits (3 monthly first 2 years, 6 monthly until 5th year) with history focused on symptoms and side effects – recording of adverse events according to CTCAEv 4.0; 5. Health care costs ‐ EC‐related healthcare costs will include the costs of the randomised care and care associated with (serious) adverse events. Healthcare use over the follow‐up period will be converted to costs using standard prices, discounted over time. Costs will be evaluated at each follow‐up and at recurrence by recording hospital admissions, surgeries, etc over the past follow‐up period INCLUSION CRITERIA: Histologically confirmed endometrioid type endometrial carcinoma, FIGO 2009 stage I, with one of the following combinations of stage, grade, age, and LVSI: 1. Stage IA, grade 3 (any age, with or without LVSI) 2. Stage IB, grade 1 or 2 and age >60 years 3. Stage IB, grade 1‐2 with documented LVSI 4. Stage IB, grade 3 without LVSI 5. Stage II (microscopic), grade 1 WHO‐performance status 0‐2 Written informed consent