Background The Cancer Genome Atlas (TCGA) project has shed light on the vital role of tumour molecular features in predicting endometrial cancer (EC) patients’ survival. This study aims to investigate the survival impact of surgical approaches on EC patients with different molecular features.

Methodology 473 eligible EC patients from TCGA database were selected. Clinicopathological characteristics and genetic features of open and minimally invasive surgery (MIS) group were compared. To analyse the prognostic impact of surgical approach, survival analyses were conducted in patients with different genetic alterations. Finally, a simplified model based on molecular features was established to help select patients suitable for MIS or open surgery.

Results In the eligible patients, 291 (61.5%) received open surgery and 182 (38.5%) received MIS. Clinicopathological and genetic features were comparable between the two groups except the year of diagnosis (p<0.001). Among all patients, 4 genetic features (POLE mutation [POLEmt], microsatellite-instability high [MSI-H], homologous recombination defect [HRD], MUC16 mutation [MUC16mt]) showed significant overlap. In Kaplan-Meier survival analyses, MIS and open surgery brought similar survival outcome in patients with POLEmt, MSI-H, HRD or MUC16mt. But in POLE wild type, non MSI-H, non HRD, or MUC16 wild type patients, MIS resulted in shorter recurrence-free survival (RFS) (p=0.008, 0.015, 0.003, 0.008). Based on TCGA classification, POLE ultramutated and MSI hypermutated type had similar prognosis after two surgeries, while copy-number low type without CTNNB1 mutation and copy-number high type with TP53 mutation showed more rapid recurrence after MIS (p=0.048 and 0.037). Further analyses were done to simplify the model. In patients with ≥1 of the 4 features (POLEmt, MSI-H, HRD or MUC16mt), MIS and open surgery brought comparable overall survival and RFS (p=0.339 and 0.969); for patients with none of the features, especially those with wild type CTNNB1 or TP53 mutation, longer RFS was observed in open surgery group (p=0.001, <0.001, <0.001, respectively). All the results of Kaplan-Meier analyses were verified by Cox regressions.

Conclusion The molecular features of EC are related to patients’ prognosis after different surgical approaches. MIS should be recommended in patients with POLEmt, MSI-H, HRD or MUC16mt for similar survival outcome and less perioperative complications compared to open surgery.

Disclosures This work was supported by the National Natural Science Foundation of China (81972426, 81202041, 81672571, 81874108 and 81802607), Special Projects for Strengthening Basic Research of Peking University (BMU2018JC005), National Key Technology R&D Program of China (2019YFC1005200 and 2019YFC1005201).

The authors have no potential conflict of interest to disclose.