A novel biomarker panel of HE4 and D-dimer improves ovarian cancer
diagnosis in postmenopausal women presenting with symptomatic pelvic
masses: a prospective cohort study
Abstract
Objective: Cancer Antigen 125 (CA125), the biomarker in common clinical
use for ovarian cancer, is limited by low sensitivity for early disease
and high false positives. The aim of this study was to evaluate several
candidate biomarkers, alone or in combination, compared to CA125.
Design: A prospective observational cohort study Setting: St. James’s
Hospital (SJH), a tertiary referral centre for gynaecological malignancy
in Dublin, Ireland. Population: 274 patients undergoing surgery for
symptomatic pelvic masses between 2012 and 2018. Methods: Preoperative
Human Epididymis Protein 4 (HE4), the Risk of Ovarian Malignancy
Algorithm, the Risk of Malignancy Index I and II, D-dimer, and
fibrinogen were assessed. Logistic regression models were fitted for
each biomarker alone and in combination. AUCs and pAUCs in the 90-100%
specificity range were determined. Main Outcome measures: The accuracy
of biomaker(s) in the prediction of malignant/borderline versus benign
tumour status compared to CA125. Results: 89 pre- and 185
post-menopausal women were included. In premenopausal women, no
biomarker(s) outperformed CA125 (AUC 0.73; 95% CI 0.63-0.84). In
postmenopausal women, HE4 had a pAUC of 0.71 (95% CI 0.64-0.79)
compared with 0.57 (95% CI 0.51-0.69) for CA125 (p = 0.009). HE4 +
D-dimer had an improved pAUC of 0.74 (95% CI 0.68-0.81, p <
0.001). Conclusion: A novel biomarker panel of HE4 + D-dimer
outperformed CA125 alone as a high specificity biomarker in
postmenopausal women and could aid in the preoperative triaging of
symptomatic pelvic masses.