Lymphovascular space invasion in endometrial carcinoma: A prognostic factor independent from molecular signature

Background: The 2020 ESGO/ESTRO/ESP guidelines stratify the prognosis of endometrial carcinoma (EC) patients combining The Cancer Genome ATLAS (TCGA) molecular signature and pathological factors, including lymphovascular space invasion (LVSI). However, little is known about the prognostic independence of LVSI from molecular signature. Aim: To assess whether the prognostic value of LVSI is independent from the TCGA signature. Material and methods: A systematic review and meta-analysis was performed by searching 5 electronic databases from their inception to March 2021. All peer-reviewed studies reporting assessing LVSI as a prognostic factor independent from the TCGA groups in EC were included. Multivariate HRs with 95% confidence interval (CI) were pooled separately for overall survival (OS), disease-specific survival (DSS) and disease-free survival (DFS). The absence of LVSI was considered as a reference. In DFS analyses, locoregional and distant recurrence were separately considered for one study. Results: Six studies with 3331 patients were included in the systematic review and three studies with 2276 patients in the meta-analysis. LVSI showed a pooled multivariate HR of 1.818 (CI 95%, 1.378–2.399) for OS, 1.849 (CI 95%, 1.194–2.863) for DSS, 1.377 (CI 95%, 1.008–1.880) for DFS excluding one study, 1.651 (CI 95%, 1.044–2.611) for DFS additionally considering locoregional recurrence from one study, and 1.684 (CI 95%, 1.05–2.701) for DFS additionally considering distant recurrence from the same study. Conclusion: LVSI has a prognostic value independent of TCGA signature, as well as age and adjuvant treatment, increasing the risk of death of any cause, death due to EC and recurrent or progressive disease by 1.5–2 times.