AIM: To develop and validate a biomarker-based index to optimize referral and diagnosis of patients with suspected ovarian cancer. Furthermore, to compare this new index with the Risk of Malignancy Index (RMI) and Risk of Ovarian Malignancy Algorithm (ROMA). PATIENTS AND METHODS: A training study, consisting of patients with benign ovarian disease (n=809) and ovarian cancer (n=246), was used to develop the Copenhagen Index (CPH-I) utilizing the variables serum HE4, serum CA125 and patient age. Eight international studies provided the validation population; comprising 1060 patients with benign ovarian masses and 550 patients with ovarian cancer. RESULTS: Overall, 2665 patients were included. CPH-I was highly significant in discriminating benign from malignant ovarian disease. At the defined cut-off of 0.070 for CPH-I the sensitivity and specificity were 95.0% and 78.4% respectively in the training cohort and 82.0% and 88.4% in the validation cohort. Comparison of CPH-I, ROMA and RMI demonstrated area-under-curve (AUC) at 0.960, 0.954 and 0.959 respectively in the training study and 0.951, 0.953 and 0.935 respectively in the validation study. Using a sensitivity of 95.0%, the specificities for CPH-I, ROMA and RMI in the training cohort were 78.4%, 71.7% and 81.5% respectively, and in the validation cohort 67.3%, 70.7% and 69.5% respectively. CONCLUSION: All three indices perform well at the clinically relevant sensitivity of 95%, but CPH-I, unlike RMI and ROMA, is independent of ultrasound and menopausal status, and may provide a simple index to optimize referral of women with suspected ovarian cancer.

Abbott Diagnostics USA

Barts Cancer Institute Queen Mary University of London John Vane Science Centre London UK; Department of Women's Cancer UCL EGA Institute for Women's Health University College London London UK

Cancer Research UK Cambridge Institute Li Ka Shing Centre Robinson Way Cambridge UK

Department of Gynecologic Oncology Center for Gynecologic Oncology Amsterdam Antoni van Leeuwenhoek Hospital The Netherlands

Department of Gynecologic Oncology Masaryk Memorial Cancer Institute Brno Czech Republic

Department of Gynecology and Obstetrics Innsbruck Medical University Innsbruck Austria

Department of Gynecology Rigshospitalet University of Copenhagen Copenhagen Denmark

Department of Laboratory Medicine Masaryk Memorial Cancer Institute Brno Czech Republic

Department of Obstetrics and Gynecology Institute of Clinical Sciences Sahlgrenska Cancer Center University of Gothenburg Gothenburg Sweden

Department of Obstetrics and Gynecology MCU FDT Medical Foundation Philippines

Department of Obstetrics and Gynecology Skåne University Hospital Lund Sweden

Department of Pathology Molecular Unit Herlev University Hospital University of Copenhagen Herlev Denmark

Department of Pathology Molecular Unit Herlev University Hospital University of Copenhagen Herlev Denmark; Department of Gynecology Rigshospitalet University of Copenhagen Copenhagen Denmark

Finsen Laboratory Rigshospitalet University of Copenhagen Copenhagen Denmark; Biotech Research and Innovation Center University of Copenhagen Copenhagen Denmark

Gynecologic Oncology Unit La Paz University Hospital Madrid Spain

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Adjustment of serum HE4 to reduced glomerular filtration and its use in biomarker-based prediction of deep myometrial invasion in endometrial cancer