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Serum HE4 predicts progestin treatment response in endometrial cancer and atypical hyperplasia: a prospective observational study
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  • Chloe Barr,
  • Heather Agnew,
  • James Bolton,
  • rhona mcvey,
  • Emma Crosbie
Chloe Barr
Manchester University NHS Foundation Trust

Corresponding Author:chloe.barr@mft.nhs.uk

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Heather Agnew
Manchester University NHS Foundation Trust
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James Bolton
Manchester University NHS Foundation Trust
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rhona mcvey
Manchester University NHS Foundation Trust
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Emma Crosbie
The University of Manchester
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Abstract

Abstract Objective: To investigate serum human epididymis-4 (HE4) as a predictive biomarker of intrauterine progestin response in endometrial cancer and atypical endometrial hyperplasia (AEH). Design: Prospective observational study. Setting: Consecutive sample of women attending a tertiary gynaecological oncology centre in the North West of England. Population: Women with AEH or early stage, low grade endometrial cancer who were unfit or declined primary surgical management; 48 in the discovery cohort and 28 in the validation cohort. Methods: Women were treated with a levonorgestrel intrauterine system (LNG-IUS) for 12 months. Endometrial biopsies and imaging were performed to assess treatment response. Pre-treatment serum HE4 was analysed by chemiluminescence immunoassay and diagnostic accuracy and logistic regression analyses performed. Main outcome measure: Progestin response at 12 months defined by histology and imaging. Results: Baseline serum HE4 was significantly higher in non-responders than responders in both discovery [134.6pmol/L (IQR:94.0-292.4) vs 76.5pmol/L (IQR:59.7-87.3), p<0.001] and validation cohorts [108.2pmol/L (IQR:80.3-119.2) vs 64.4pmol/L (IQR:53.0-73.0), p=0.004]. An HE4≥77pmol/L had a sensitivity and specificity for progestin treatment response of 83.3% and 53.3% in the discovery cohort, and 85.7% and 76.2% and in the validation cohort, respectively. When expressed as a continuous variable, the AUC was 0.81 (95%CI:0.67-0.95) and 0.87 (95%CI:0.73-1.00) for the discovery and validation cohorts, with every 1pmol/L of HE4 increasing the likelihood of progestin treatment failure by 2% and 5%, after adjustment for age and histology, respectively (p=0.02 and p=0.18). Conclusion: Serum HE4 shows promise as a predictive biomarker of progestin treatment response in endometrial cancer and AEH.
08 Aug 2022Submitted to BJOG: An International Journal of Obstetrics and Gynaecology
12 Aug 2022Assigned to Editor
12 Aug 2022Submission Checks Completed
15 Aug 2022Reviewer(s) Assigned
13 Sep 2022Review(s) Completed, Editorial Evaluation Pending
03 Oct 2022Editorial Decision: Revise Major
30 Nov 20221st Revision Received