Serum HE4 predicts progestin treatment response in endometrial cancer and atypical hyperplasia: A prognostic study

To investigate serum human epididymis-4 (HE4) as a predictive biomarker of intrauterine progestin response in endometrial cancer and atypical endometrial hyperplasia (AEH).

Prospective prognostic factor study.

Consecutive sample of women attending a tertiary gynaecological oncology centre in northwest England.

Women with AEH or early-stage, low-grade endometrial cancer who were unfit for or declined primary surgical management.

A total of 76 women, 32 with AEH and 44 with endometrial cancer, were treated with a levonorgestrel intrauterine system (LNG-IUS) for 12 months. Endometrial biopsies and imaging were performed to assess treatment response. Pretreatment serum HE4 was analysed by chemiluminescence immunoassay and diagnostic accuracy and logistic regression analyses were performed.

Progestin response at 12 months defined by histology and imaging.

The median age and body mass index (BMI) of the final cohort were 52 years (interquartile range [IQR] 33-62 years) and 46 kg/m² (IQR 38-54 kg/m² ), respectively. Baseline serum HE4 was significantly higher in non-responders than responders (119.2 pmol/L, IQR 94.0-208.4 pmol/L versus 71.8 pmol/L, IQR 56.1-84.2 pmol/L, p < 0.001). Older age (odds ratio [OR] 0.96, 95% CI 0.93-0.99, p = 0.02), baseline serum HE4 (OR 0.97, 95% CI 0.96-0.99, p = 0.001) and endometrial cancer histology (OR 0.22, 95% CI 0.72-0.68, p = 0.009) were associated with a lower likelihood of progestin treatment response. Serum HE4 remained independently associated with progestin treatment failure when adjusted for age and histology (adjusted hazard ratio 0.97, 95% CI 0.96-0.99, p = 0.008).

Serum HE4 shows promise as a predictive biomarker of progestin treatment response in endometrial cancer and AEH.