Lymph-Vascular Space Invasion (Lvsi) As A Strong And Independent Predictor For Non-Locoregional Recurrences In Endometrial Cancer: A Danish Gynecological Cancer Group Study

Objective: To evaluate the effect of lymph-vascular space invasion (LVSI) on location of recurrences in Danish patients with endometrial cancer.Methods: This national cohort study (2005-2012) included 4,380 radically operated patients (no visual tumor, all distant metastasis removed). LVSI status was recorded in 3,377 (77.1%). In stage I patients, 2.6% received adjuvant radiotherapy and 1.4% adjuvant chemotherapy. Adjusted Cox regression was used to compare actuarial recurrence rates.Results: LVSI was present in 18.7% of 3,377 patients with known LVSI status. Of these, 7.6% stage I patients with LVSI experienced an isolated locoregional and 19.4% a non-locoregional recurrence. Compared to no LVSI, 5-year recurrence rate was higher (25.5% vs. 8.5%) in patients with LVSI and the frequency of distant recurrences was strikingly higher (stage I: 15.2% vs. 2.7%), the effect being similar across International Federation of Gynecology and Obstetrics stages and histological types. In intermediate-risk stage I patients with LVSI, 8.0% experienced an isolated locoregional recurrence compared to 20.1% with non-locoregional recurrence, giving these patients a seriously adverse risk of survival. A separate analysis in patients with recurrences demonstrated that those with LVSI had significantly more distant recurrences (55.4% vs. 29.9%) and fewer isolated vaginal recurrences (24.3% vs. 42.8%) than patients with no LVSI.Conclusion: LVSI is a strong independent risk factor for the development of non-locoregional recurrences even in intermediate-risk stage I endometrial cancer. The non-locoregional recurrence pattern suggests a future focus for optimization of postoperative treatment in these patients.