PErsonalized TReatment for Endometrial Carcinoma (PETREC): study design and methods of a prospective Finnish multicenter trial

Abstract

Background: Endometrial carcinomas can be classified into four molecular subgroups - mismatch repair deficient (MMRd), p53 abnormal (p53abn), polymerase-ϵ (POLE) ultramutated, and 'no specific molecular profile' (NSMP). Retrospective data imply that the response to adjuvant therapies may depend on the molecular subgroup. These findings emphasize the need for adjuvant therapy trials where patients are randomized to treatment arms separately within each molecular subgroup.

Primary objective: The PErsonalized TReatment for Endometrial Carcinoma (PETREC) trial clarifies the value of molecular classification in the determination of adjuvant therapies of high-intermediate risk and early-stage high-risk endometrial carcinoma.

Study hypothesis: Compared with vaginal brachytherapy, the utilization of whole pelvic radiotherapy may result in improved outcomes for either MMRd or NSMP high-intermediate risk carcinomas. Early-stage high-risk p53abn and nonendometrioid carcinomas are postulated to gain benefits from chemoradiotherapy, as opposed to chemotherapy alone. POLE ultramutated carcinomas harboring high-intermediate or high-risk clinicopathologic features are speculated to have favorable prognosis without any adjuvant therapy.

Trial design: This prospective, multicenter, phase 3 trial compares the efficacy of vaginal brachytherapy vs whole pelvic radiotherapy in high-intermediate risk MMRd and NSMP molecular subgroups, and chemotherapy vs chemoradiotherapy in early-stage high-risk p53abn subtype and nonendometrioid carcinomas. Eligible women who consent to participation in the trial are randomly allocated (1:1) to treatment arms.

Major inclusion/exclusion criteria: Women with stages I-II molecular integrated high-intermediate risk or high-risk endometrial carcinoma will be included.

Primary endpoint: The primary endpoint is the 5 year cumulative incidence of disease recurrence.

Sample size: A total sample size of 294 patients (49 subjects in each treatment arm of the three subgroups intended for randomization) was estimated to be sufficient.

Estimated dates for completing accrual and presenting results: Patient recruitment will be completed in 2025, and follow-up will be completed in 2030.

Trial registration: NCT05655260.

Keywords: Endometrium; Uterine Cancer.