Prognostic value of myometrial invasion and TCGA groups of endometrial carcinoma

Background: 2021 ESGO/ESTRO/ESP guidelines for the management of patients with endometrial carcinoma (EC) encourage molecular classification and propose a new prognostic risk stratification based on both pathologic and molecular features. Although deep myometrial invasion (DMI) has been considered as a crucial risk factor in EC, it is unclear if its prognostic value is independent from The Cancer Genome ATLAS (TCGA) groups. Aim: To assess if the prognostic value of DMI is independent from the TCGA groups in EC patients. Materials and methods: A systematic review and meta-analysis was performed by searching through 5 electronic databases, from their inception to March 2021, for all studies that allowed to assess DMI as a prognostic factor independent of the TCGA groups in EC patients. Pooled hazard ratio (HR) of DMI for overall survival (OS) and disease-free survival (DFS) was calculated at multivariable analyses including TCGA groups as a variable. Superficial myometrial invasion (<50% of myometrial thickness) was considered as a reference. In DFS analyses, locoregional and distant recurrence were separately considered for one study. Results: Five studies with 2469 patients were included in the systematic review and 3 studies with 1549 patients in the meta-analysis. Pooled HR of DMI was 1.082 (CI 95% 0.85–1.377; p = 0.524) for OS, 1.709 (CI 95% 1.173–2.491; p = 0.005) for DFS, 1.585 (CI 95% 1.154–2.178; p = 0.004) for DFS additionally considering locoregional recurrence for one study, and 1.701 (CI 95% 1.235–2.344, p = 0.001) for DFS additionally considering distant recurrence for the same study. Conclusions: DMI does not appear as an independent prognostic factor for OS in EC patients; instead, it seems to affect the risk of recurrence independently from the TCGA groups. Further studies are necessary to confirm these findings and to assess the prognostic impact of DMI separately in each TCGA group.