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 in the prediction of malignant/borderline vs benign tumor status in pre- and post-menopausal women with pelvic masses.
This was a retrospective observational cohort study set in St. James’s Hospital, a tertiary referral centre for gynecological malignancy in Dublin, Ireland. Women undergoing surgery for pelvic masses between 2012 and 2018 were included. 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. Receiver operating characteristic- area under the curve (ROC-AUC) and partial AUCs in the 90-100% specificity range were determined.
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) and HE4 + D-dimer + Fibrinogen had a pAUC of 0.75 (95% CI 0.68-0.82).
A novel biomarker panel of HE4 ± D-dimer ± Fibrinogen outperformed CA125 alone as a high specificity biomarker in postmenopausal women and could aid in the preoperative triaging of pelvic masses. No biomarker(s) outperformed CA125 in pre-menopausal women.