Objectives About 10–66% of patients with atypical endometrial hyperplasia diagnosed before surgery (pre-AEH) are found to have concurrent endometrial cancer (EC) after definitive hysterectomy, leading to incomplete primary surgery and delayed adjuvant treatment. This study aims to investigate which factors could predict underlying cancer risk in pre-AEH patients.

Methods All patients diagnosed with AEH by endometrial sampling and then underwent definitive hysterectomy from January 2016 to December 2019 were identified. Patients diagnosed with EC by final pathology were divided into 2 subgroups according to NCCN guideline 2021: low-risk, and intermediate-high risk.

Results Totally 624 pre-AEH patients were identified, 30.4% (n=190) of them were diagnosed with EC finally. Univariate analysis showed underlying risk of EC was correlated with postmenopausal status, higher CA125 serum level (≥ 35U/ml), higher serum level of fast blood glucose (≥ 7.0 mmol/L) and older age (>50 years old). In multivariate analysis, only postmenopausal status and CA125 ≥ 35 U/ml (OR = 3.89, 95% CI = 1.59–9.53; OR = 3.11, 95% CI = 1.13–8.59) independently predicted concurrent EC. Remarkably, patients with postmenopausal status + CA125 ≥ 35 U/ml had significantly increased risk of finally-diagnosed EC (OR = 14.10, 95% CI = 1.59–125.22). Similar results were also found in predicting intermediate-high-risk EC. Notably, among all the postmenopasal patients, pre-AEH women with postmenopausal time ≥ 5years were found to have highest risk of concurrent EC.

Conclusions Pre-AEH patients with postmenopausal status and elevated level of CA125 may have high risk of concurrent EC. More detailed evaluation before surgery should be suggested.