Outcomes of low-risk endometrial cancer with isolated tumor cells in the sentinel lymph nodes: a prospective, multi-center, single-arm, observational study (ENDO-ITC study)

Background: It is unclear whether isolated tumor cells (ITCs) in sentinel lymph nodes (SLNs) adversely affect prognosis, especially in low-risk endometrial cancer. In a retrospective study, we showed a worse recurrence-free survival for low-risk endometrial cancer with ITCs than the node-negative group. Primary Objective: Our aim is to evaluate whether the likelihood of disease recurrence differs between a prospective cohort of patients with low-risk endometrial cancer with ITCs and an historical cohort with negative SLNs. Study Hypothesis: We hypothesize that patients with low-risk endometrial cancer and ITCs will have a worse recurrence-free survival than patients who are node-negative. Trial Design: This is a prospective, multi-center, single-arm observational study. Consecutive patients with low-risk endometrial cancer with ITCs in the SLNs will be accrued. Observation only will be suggested after surgery. Major Inclusion/Exclusion Criteria: We will include patients with endometrial cancer undergoing pelvic SLN biopsy and ultra-staging with the following characteristics: endometrioid histology, grades 1 to 2, <50% myometrial invasion, without substantial/extensive lympho-vascular space invasion. ITCs in SLNs are defined as tumor cell aggregates ≤0.2 mm or <200 cells. Primary End Point: The primary end point is recurrence-free survival, measured from the date of surgery to the date of recurrence, death, or last disease evaluation. Sample Size: With a sample size of 132 women with low-risk endometrial cancer and ITCs, a 1-sided log-rank test achieves 85% power at a 0.05 significance level to detect an HR of 2.1. The expected number of events during the study is 17.3. Estimated Dates for Completing Accrual and Presenting Results: The study duration will be 60 months: 24 for enrollment and 36 for follow-up. The results are expected in 2029. Trial Registration: ClinicalTrials.gov: NCT06689956.