Serum HE4 Detects Recurrent Endometrial Cancer in Patients Undergoing Routine Clinical Surveillance

Background: The purpose of this study was to evaluate serum HE4 as a biomarker to detect recurrent disease during follow-up of patients with endometrial adenocarcinoma (EAC).

Methods: We performed a retrospective analysis of 98 EAC patients treated at Innsbruck Medical University, between 1999 and 2009. Twenty-six patients developed recurrent disease. Median follow-up was 5 years. Serum HE4 and CA125 levels were analyzed using the ARCHITECT assay (Abbott, Wiesbaden, Germany) pre-operatively (baseline), post-operative (interval) and after histological confirmation of recurrent disease or when patients returned for clinical review with no evidence of recurrent disease (recurrence/final)). Receiver operator curves (ROC), Spearman rank correlation coefficient, chi-squared and Mann-Whitney tests were used for statistical analysis.

Results: HE4 levels decreased after initial treatment (p = 0.001) and increased again at recurrence (p = 0.002). HE4 was elevated (>70 pmol/L) in 21 of 26 (81%) and CA125 was elevated (>35 U/ml) in 12 of 26 (46%) patients at recurrence. In endometrioid histology (n = 69) serum HE4 measured during follow up (Area under the curve (AUC) = 0.87, 95%CI 0.79-0.95) was a better indicator of recurrence than CA125 (AUC = 0.67, 95%CI 0.52-0.83). A HE4 level of 70 pmol/L was associated with a sensitivity of 84%, a specificity of 74% and a negative predictive value of 93% when assessing for recurrent endometrioid EAC.

Conclusion: This is a preliminary description of HE4 serum levels measured during routine follow up of EAC patients. Serum HE4 measured during clinical follow-up may identify recurrent disease particularly in patients with endometrioid histology. Further prospective validation of HE4 is warranted.