The goal of this clinical trial is to compare the efficacy of adjuvant therapies in women with stage I-II molecular integrated high-intermediate or high-risk endometrial carcinoma. Specifically, the invesigators want to compare:

• Chemotherapy vs. chemoradiotherapy in p53 abn subtype and nonendometrioid carcinomas.
• Vaginal brachytherapy vs. whole pelvic radiotherapy in the MMR-D molecular subgroup.
• Vaginal brachytherapy vs. whole pelvic radiotherapy in the NSMP molecular subgroup.

Endometrial carcinomas can be classified into four molecular subgroups, i.e. mismatch repair deficient (MMR-D), p53 abnormal (p53 abn), polymerase-ϵ (POLE) ultramutated, and "no specific molecular profile" (NSMP). Molecular subgroups can be considered to be distinct diseases as they are associated with different clinicopathologic characteristics, prognoses and, possibly, responses to adjuvant therapy. Molecular classification of endometrial carcinoma is recommended to be implemented in routine clinical practice to improve prognostication and triage to adjuvant therapy. The PErsonalized TReatment for Endometrial Carcinoma (PETREC) trial, led by the Finnish Gynecologic Oncology Group (FINGOG), is a multicenter prospective clinical trial for women with stage I-II molecular integrated high-intermediate or high-risk endometrial carcinoma. The efficacy of chemotherapy vs. chemoradiotherapy is compared in p53 abn subtype and nonendometrioid carcinomas, and vaginal brachytherapy vs. whole pelvic radiotherapy in MMR-D and NSMP molecular subgroups. Patients who consent to follow-up within the trial but not to randomization are treated as recommended in multidisciplinary meetings and enrolled for follow-up only (comprehensive cohort study design). The primary outcome is the 5-year cumulative incidence of disease recurrence. Secondary outcomes are vaginal, pelvic, and distant recurrence rates, 5-year recurrence-free and overall survival, adverse events, and patient-reported symptoms and quality of life. The findings of the trial may eventually help decrease under- and overtreatment and, consequently, improve patient outcome and decrease treatment-associated adverse effects.

Inclusion Criteria:

• Age 18 to 100 years
• WHO performance status 0 to 2
• Stage I-II molecular integrated high-intermediate or high-risk endometrial carcinoma

Exclusion Criteria:

• Age <18 years or >100 years
• WHO performance status >2
• Uterine sarcoma
• A history of malignancy within 5 years
• Previous pelvic radiotherapy
• An interval of >30 days between surgery and start of chemotherapy or >8 weeks between surgery and start of radiotherapy (longer intervals may be permitted with investigator´s approval)

Eligibility not based on self-representation of gender identity.