Preoperative markers for the prediction of high-risk features in endometrial cancer

Preoperative evaluations aiming to assess high-risk features in clinical stage 1 endometrial cancer patients are crucial to refer these patients to gynecologic oncologists. Cancer antigen 125 (CA125) and human epididymis protein 4 (HE4) have been reported in endometrial cancer patients with poor prognostic factors.

To evaluate the association between preoperative levels of CA125 and HE4 and high-risk features and establish optimal cut-off values in clinical stage 1 endometrial cancer.

A retrospective study was conducted in clinical stage 1 endometrial cancer patients who underwent primary surgery between January 2013 and December 2018. A total of 128 patients had preoperative serum CA125 and HE4 measurements. High-risk features included grade 3 tumors, large tumor sizes (more than 2 cm), deep myometrial invasion (more than 50%), lymphovascular space invasion (LVSI), cervical involvement, extrauterine involvement and node metastasis. Receiver operating characteristic (ROC) curves were generated to analyze the optimal cut-off values.

The mean age of the patients was 57.4 years, and 69.5% of them were postmenopausal. Most patients presented with stage I disease (67.2%) and had the endometrioid subtype (97.7%). The median CA125 and HE4 levels in all patients were 22.1 U/mL and 104.7 pmol/L, respectively. CA125 and HE4 levels were significantly elevated in those with large tumor sizes, deep myometrial invasion, LVSI, extrauterine metastasis, and advanced stage, but node metastasis was associated with elevated CA125 only. According to the ROC curve, both serum markers had statistical significance for the prediction of high-risk features only in postmenopausal patients, with an optimal cut-off value of 20 U/mL for CA125 [area under the concentration-time curve (AUC) = 0.72, P = 0.002] and 113 pmol/L for HE4 (AUC = 0.70, P = 0.006). The combination of both serum markers had 80% sensitivity and 64.4% positive predictive value. Significantly worse 5-year disease-free survival was observed in patients with high levels of CA125 and HE4 (78.4% and 100%, respectively; P = 0.01).

Preoperative CA125 levels greater than 20 U/mL or HE4 levels greater than 113 pmol/L are associated with an increased risk of having high-risk features and present as prognostic factors in clinical stage 1 postmenopausal endometrial cancer patients. This information is helpful for general gynecologists to refer high-risk patients to gynecologic oncologists to perform complete surgical staging.