Refining Adjuvant Treatment IN Endometrial Cancer Based On Molecular Features

RAINBO MMRd-GREEN is an international, multicenter, phase III randomised trial wherein adjuvant pelvic external beam radiotherapy combined with and followed by durvalumab for one year is compared to adjuvant pelvic external beam radiotherapy with or without chemotherapy.

Participants of the four RAINBO trials should be eligible according to the inclusion and exclusion criteria of both the overarching RAINBO trials program and the clinical trial that they are assigned to based on the molecular profile. Inclusion Criteria of the overarching RAINBO program: * Histologically confirmed diagnosis of endometrial cancer (EC) of the following histotypes: endometrioid endometrial carcinoma, serous endometrial carcinoma, uterine clear cell carcinoma, dedifferentiated and undifferentiated endometrial carcinoma, uterine carcinosarcoma and mixed endometrial carcinomas of the aforementioned histotypes. * Full molecular classification performed following the diagnostic algorithm described in WHO 2020 (5th Edition, IARC, Lyon, 2020) * TLH-BSO or TAH-BSO with or without lymphadenectomy or sentinel node biopsy, without macroscopic residual disease after surgery * No distant metastases as determined by pre-surgical or post-surgical imaging (CT/MRI scan of chest, abdomen and pelvis or PET-CT scan) * Age ≥ 18 years * Expected start of adjuvant treatment (if applicable) within 10 weeks after surgery * Patients must be accessible for treatment and follow-up * Written informed consent for participation in one of the RAINBO trials, permission for the contribution of a tissue block for translation research and permission for the use and sharing of data for the overarching research project according to the local Ethics Committee requirements. Exclusion Criteria overarching RAINBO program: * History of another primary malignancy, except for non-melanoma skin cancer, in the past 5 years * Prior pelvic radiation The MMRd-GREEN trial Inclusion criteria: * Written informed consent * WHO Performance score 0-1 * Histologically confirmed FIGO 2009 stage IB/II with LVSI, stage III, or stage IV with limited pelvic peritoneal involvement (FIGO 2023 stage IB with LVSI, stage II with myometrial or cervical stroma involvement and LVSI, or stage III disease) * Molecular classification: MMRd EC\* * No prior pelvic radiotherapy * Body weight \> 30 kg * Adequate systemic organ function: * Creatinine clearance (\> 40 cc/min): Measured creatinine clearance (CL) \>40 mL/min or Calculated creatinine CL\>40 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance. * Adequate bone marrow function : hemoglobin \>9.0 g/dl, Absolute neutrophil count (ANC) ≥1.0 x 109/l, platelet count ≥75 x 109/l. * Adequate liver function: Bilirubin ≤1.5 x institutional upper limit of normal (ULN). \