Prominent Lymphovascular Space Invasion as an Independent Prognostic Factor in LVSI-Positive Endometrioid Endometrial Carcinoma: Evidence for a Novel Three-Tiered Classification

Background/Objectives: Lymphovascular space invasion (LVSI) is an established prognostic factor in endometrial cancer, yet current risk stratification relies on a binary focal/substantial classification. Whether further substratification into a “prominent” LVSI category (≥10 involved vessels) provides independent prognostic value beyond the FIGO 2023 staging framework remains unclear. We aimed to investigate the prognostic significance and clinical outcomes regarding the extent of lymphovascular space invasion (LVSI) in patients with LVSI-positive endometrioid endometrial cancer (EEC). Methods: We retrospectively identified 94 patients with International Federation of Gynecology and Obstetrics (FIGO) 2009 stage I–IV EEC who underwent surgical staging. LVSI-positive cases were classified as focal (1–4 involved vessels), substantial (5–9 involved vessels), or prominent (≥10 involved vessels). Results: Of the 94 LVSI-positive patients, 58 (61.7%) had focal, 11 (11.7%) had substantial, and 25 (26.6%) had prominent LVSI. Five-year overall survival (OS) rates were 95.3%, 72.7%, and 53.0% for focal, substantial, and prominent LVSI, respectively (p < 0.001), with corresponding progression-free survival rates of 87.6%, 71.6%, and 34.3% (p < 0.001). On multivariable analysis, prominent LVSI emerged as an independent predictor of both mortality (HR 14.31, p < 0.001) and disease progression (HR 4.02, p = 0.009), retaining significance after re-assessment for FIGO 2023 stage. Tumor size > 4 cm and p53-abnormal status were also independently associated with OS. Conclusions: Prominent LVSI was independently associated with aggressive disease and poor survival in EEC; recognizing its extent as a prognostic parameter may improve both clinical management and future risk classification frameworks. As these findings are derived from a single-institution, LVSI-positive cohort with an empirically defined threshold, external validation is warranted before clinical adoption.