Lymphovascular Space Invasion in Early-Stage Endometrial Cancer (LySEC): Patterns of Recurrence and Predictors. A Multicentre Retrospective Cohort Study of the Spain Gynecologic Oncology Group

SIMPLE SUMMARY: In patients with early-stage endometrioid endometrial cancer, the presence of lymph vascular space involvement (LVSI) correlates with nodal metastases, shorter disease-free survival and overall survival. However, the effect of LVSI on recurrence patterns of these patients has been poorly studied, and the optimal adjuvant treatment remains unclear. Additionally, positive LVSI is indicative for nodal assessment, however, this parameter is usually not Known until a final pathology report. The main aim of our study was to analyze oncological outcomes and patterns of recurrence of these patients according to LVSI status, as well as to determine preoperative predictors of positive LVSI. We confirmed in a large multi-institutional cohort of patients (3546 participants), that positive LVSI is an independent prognostic factor for distant recurrences (HR 2.37) but not for local recurrence. In addition, deep myometrial invasion, high-grade tumors, cervical stroma invasion, and tumor diameter ≥ 2 cm are independent predictors of positive LVSI. ABSTRACT: The main aim is to compare oncological outcomes and patterns of recurrence of patients with early-stage endometrioid endometrial cancer according to lymphovascular space invasion (LVSI) status. The secondary objective is to determine preoperative predictors of LVSI. We performed a multicenter retrospective cohort study. A total of 3546 women diagnosed with postoperative early-stage (FIGO I-II, 2009) endometrioid endometrial cancer were included. Co-primary endpoints were disease-free survival (DFS), overall survival (OS), and pattern of recurrence. Cox proportional hazard models were used for time-to-event analysis. Univariate and multivariate logistical regression models were employed. Positive LVSI was identified in 528 patients (14.6%) and was an independent prognostic factor for DFS (HR 1.8), OS (HR 2.1) and distant recurrences (HR 2.37). Distant recurrences were more frequent in patients with positive LVSI (78.2% vs. 61.3%, p < 0.01). Deep myometrial invasion (OR 3.04), high-grade tumors (OR 2.54), cervical stroma invasion (OR 2.01), and tumor diameter ≥ 2 cm (OR 2.03) were independent predictors of LVSI. In conclusion, in these patients, LVSI is an independent risk factor for shorter DFS and OS, and distant recurrence, but not for local recurrence. Deep myometrial invasion, cervical stroma invasion, high-grade tumors, and a tumor diameter ≥ 2 cm are independent predictors of LVSI.