Prognostic significance of isolated tumor cells and nodal tumor burden in endometrial cancer: a population-based cohort study

Abstract

BACKGROUND AND PURPOSE: Since the introduction of sentinel lymph node biopsy, nodal assessment has expanded to nearly all women with endometrial cancer. However, evidence on the prognostic significance of isolated tumor cells (ITCs) and nodal tumor burden remains limited. We therefore investigated the association of ITCs and nodal tumor burden with survival. PATIENTS AND METHODS: This cohort study included women with endometrial cancer who underwent surgery in Region Stockholm-Gotland, Sweden, between 2010 and 2024, and either underwent sentinel lymph node biopsy or were registered as having lymph node metastases (FIGO stage IIIC). Nodal dissemination was categorized as bulky, macro-, micro-metastases, or ITCs. Overall survival (OS) and cancer-specific survival (CSS) were evaluated using multivariable Cox regression in two separate analyses: (1) ITCs versus node-negative patients and (2) nodal tumor burden (bulky, macro-, micro-metastases) among node-positive patients. RESULTS: Among 1219 patients, 310 (25%) had nodal dissemination, including 250 with nodal metastases and 60 with ITCs. No significant difference in OS was observed between patients with ITCs and node-negative patients (Hazard ratio [HR] 1.94, 95% confidence interval [CI] 0.75-5.06). Adjuvant therapy was more frequent among patients with ITCs (47% vs. 11%). In patients with nodal metastases, no clear OS differences were observed by nodal burden. Compared with micrometastases, survival was similar for macrometastases (HR 0.95, 95% CI 0.50-1.81) and bulky metastases (HR 1.19, 95% CI 0.64-2.21). Age > 68 years and p53 mutation were associated with worse survival. CSS analyses yielded similar findings, with no significant differences observed in either comparison. INTERPRETATION: Neither ITCs nor greater nodal burden was clearly associated with survival after adjustment for clinical and molecular factors. Survival appeared to be influenced by patient and tumor characteristics, although estimates were imprecise and modest associations cannot be excluded.