Prognostic Impact of WHO 2020 Lymphovascular Space Invasion Categories in Endometrial Cancer: Substantial LVSI as an...

To evaluate the prognostic significance of lymphovascular space invasion (LVSI), classified according to the 2020 World Health Organization (WHO) criteria, on disease-free survival (DFS) and overall survival (OS) in endometrial cancer, and to characterize the prognosis of LVSI-positive, lymph node-negative disease.

This retrospective single-center cohort study included 568 patients with endometrial carcinoma who underwent primary surgical treatment with comprehensive surgical staging, including lymph node assessment, between January 2023 and December 2025. LVSI was classified as absent, focal, or substantial. Survival outcomes were estimated by the Kaplan-Meier method and compared by log-rank test. Independent predictors of DFS and OS were identified by multivariable Cox proportional hazards regression. A four-group analysis combining LVSI and lymph node status was also performed.

LVSI was absent in 413 patients (72.7%), focal in 39 (6.9%), and substantial in 116 (20.4%). Median follow-up was 20.0 months. On multivariable analysis, substantial LVSI was an independent predictor of reduced DFS (HR 2.22, 95% CI: 1.14-4.32; p = 0.018) and OS (HR 3.48, 95% CI: 1.34-9.00; p = 0.010), whereas focal LVSI did not retain independent prognostic significance. LVSI-positive/lymph node-negative patients had significantly worse DFS than LVSI-negative/lymph node-negative patients (p < 0.001) and did not differ significantly from LVSI-negative/lymph node-positive patients (p = 0.065), suggesting recurrence outcomes approaching those of node-positive disease.

Substantial LVSI is an independent adverse prognostic factor in endometrial cancer. LVSI-positive/lymph node-negative patients demonstrated recurrence outcomes approaching those of lymph node-positive disease; given the limited follow-up, this finding is hypothesis-generating and requires prospective validation before informing treatment escalation.