Kate McKendry1,2, Stephen Duff3, Yanmei Huang1,2, Mostafa Redha4, Áine Scanlon4, Feras Abu Saadeh1,2, Noreen Gleeson1,2, John O'Leary2,5, Lucy Norris1,2, Sharon O'Toole1,2. 1. Department of Obstetrics & Gynaecology, Trinity Centre for Health Sciences, St James's Hospital, Dublin, Ireland. 2. Trinity St James's Cancer Institute, St James's Hospital, Dublin, Ireland. 3. UCD Clinical Research Centre, UCD School of Medicine, St Vincent's University Hospital, Dublin, Ireland. 4. Department of Biochemistry, Clinical Pathology Laboratory, St James's Hospital, James's Street, Dublin, Ireland. 5. Department of Histopathology, Trinity College Dublin, and Emer Casey Molecular Pathology Research Laboratory, Coombe Women's and Infants University Hospital, Dublin, Ireland.
Abstract
INTRODUCTION: CA 125, 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 with CA 125 in the prediction of malignant/borderline vs benign tumor status in premenopausal and postmenopausal women with pelvic masses. MATERIAL AND METHODS: This was a retrospective observational cohort study set in St James's Hospital, a tertiary referral center 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 characteristics-area under the curve (ROC-AUC) and partial AUCs in the 90%-100% specificity range were determined. RESULTS: In all, 89 premenopausal and 185 postmenopausal women were included. In premenopausal women, no biomarker(s) outperformed CA 125 (AUC 0.73; 95% CI 0.63-0.84). In postmenopausal women, HE4 had a partial AUC (pAUC) of 0.71 (95% CI 0.64-0.79) compared with 0.57 (95% CI 0.51-0.69) for CA 125 (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). CONCLUSIONS: A novel biomarker panel of HE4 ± D-dimer ± fibrinogen outperformed CA 125 alone as a high-specificity biomarker in postmenopausal women and could aid in the preoperative triaging of pelvic masses. No biomarker(s) outperformed CA 125 in premenopausal women.
INTRODUCTION: CA 125, 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 with CA 125 in the prediction of malignant/borderline vs benign tumor status in premenopausal and postmenopausal women with pelvic masses. MATERIAL AND METHODS: This was a retrospective observational cohort study set in St James's Hospital, a tertiary referral center 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 characteristics-area under the curve (ROC-AUC) and partial AUCs in the 90%-100% specificity range were determined. RESULTS: In all, 89 premenopausal and 185 postmenopausal women were included. In premenopausal women, no biomarker(s) outperformed CA 125 (AUC 0.73; 95% CI 0.63-0.84). In postmenopausal women, HE4 had a partial AUC (pAUC) of 0.71 (95% CI 0.64-0.79) compared with 0.57 (95% CI 0.51-0.69) for CA 125 (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). CONCLUSIONS: A novel biomarker panel of HE4 ± D-dimer ± fibrinogen outperformed CA 125 alone as a high-specificity biomarker in postmenopausal women and could aid in the preoperative triaging of pelvic masses. No biomarker(s) outperformed CA 125 in premenopausal women.