Objective The aim of this study is to analyze the prognostic role of lymph-vascular space invasion (LVSI), evaluated in a semi-quantitative fashion on prognosis of early stage, low risk endometrial cancer (EC). Methods We enrolled patients who underwent surgery for endometrial cancer between 2003 and 2018 in two referral cancer center. All patients had endometrioid EC, G1–G2, with myometrial invasion <50%, and no lymph-node involvement. LVSI was analyzed in a semi-quantitative way, according to a 3-tiered scoring system in absent, focal and substantial. Results Among 524 patients, any positive LVSI was found in 57 patients (10.9%) with focal LVSI (n=35, 6.7%) and substantial LVSI (n=22, 4.2%). Substantial LVSI was associated to higher rate of G2 (p<0.001), myometrial infiltration (p=0.002) and greater tumor dimensions (p=0.014). Patients with substantial LVSI were more likely to receive adjuvant treatment (6.6% vs. 52.6%, p<0.001). The 5-year OS was 99.5% in patients with absent LVSI and 70.6% in those with substantial LVSI (p<0.001). The 5-year disease free survival (DFS) was 93.6% in patients with absent LVSI and 56.5% in those with substantial LVSI (p<0.001). The rate of distant failures increased from 1.8% for absent LVSI to 22.7% for substantial LVSI (p=0.002). In univariate analysis substantial LVSI was the strongest predictor of poor overall survival (hazard ratio [HR]=11.9, p=0.001). Multivariate analysis showed that substantial LVSI was an independent predictive factor of both recurrence (HR=5.88, p=0.001) and distant failure (HR=10.6, p=0.006). Conclusions Substantial LVSI represents the strongest independent risk factor for decreased survival and distant relapse, indicating a role for potential hematogenous dissemination.

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