Is Substantial Lymphovascular Space Invasion Prognostic in Patients With Pathologically Lymph Node-Negative Endometrial Cancer?

Abstract

Lymphovascular space invasion (LVSI) predicts for higher rates of recurrence and increased mortality in endometrial cancer. Using three-tier LVSI scoring, a PORTEC 1&2 trials analysis demonstrated that substantial LVSI was associated with worse locoregional (LR-DFS) and distant metastasis disease free survival (DM-DFS), and these patients possibly benefited from external beam radiation therapy (EBRT). Furthermore, LVSI is a predictor for lymph node (LN) involvement, but the significance of substantial LVSI is unknown in patients with a pathologically negative LN assessment. We aimed to evaluate clinical outcomes of these patients in relation to the three-tier LVSI scoring system. We performed a single-institutional retrospective review of patients with stage I endometrioid-type endometrial cancer who underwent surgical staging with pathologically negative LN evaluation from 2017 - 2019 with three-tier LVSI scoring (none, focal or substantial). Clinical outcomes (LR-DFS, DM-DFS, and overall survival [OS]) were analyzed using Kaplan-Meier method. A total of 335 patients with pathologically LN negative stage 1 endometrioid-type endometrial carcinoma were identified. Substantial LVSI was present in 17.6% of patients. 39.7% of patients received adjuvant vaginal brachytherapy, and 6.9% of patients received EBRT. Adjuvant radiation treatment varied by LVSI status. In patient with focal LVSI, 81.0% received vaginal brachytherapy. Among patients with substantial LVSI, 57.9% received vaginal brachytherapy alone, and 31.6% of patients received EBRT. The 2-year LR-DFS rates were 92.5%, 98.0%, and 91.4% for no LVSI, focal LVSI, and substantial LVSI, respectively. The 2-year DM-DFS rates were 95.5%, 93.3%, and 93.8% for no LVSI, focal LVSI, and substantial LVSI, respectively. In our institutional study, patients with pathologically LN negative stage I endometrial cancer with substantial LVSI had similar rates of LR-DFS and DM-DFS compared to patients with none/focal LVSI. These findings highlight the need for multi-institutional studies to validate the prognostic value of substantial LVSI in this patient population.