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Gynecol Oncol. 2015 Sep;138(3):640-6. doi: 10.1016/j.ygyno.2015.06.021. Epub 2015 Jun 16.

A novel diagnostic index combining HE4, CA125 and age may improve triage of women with suspected ovarian cancer - An international multicenter study in women with an ovarian mass.

Author information

1
Department of Pathology, Molecular Unit, Herlev University Hospital, University of Copenhagen, Herlev, Denmark; Department of Gynecology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. Electronic address: mona.aarenstrup.karlsen@regionh.dk.
2
Department of Pathology, Molecular Unit, Herlev University Hospital, University of Copenhagen, Herlev, Denmark.
3
Finsen Laboratory, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark; Biotech Research and Innovation Center (BRIC), University of Copenhagen, Copenhagen, Denmark.
4
Department of Obstetrics and Gynecology, Skåne University Hospital, Lund, Sweden.
5
Department of Laboratory Medicine, Masaryk Memorial Cancer Institute, Brno, Czech Republic.
6
Department of Gynecologic Oncology, Masaryk Memorial Cancer Institute, Brno, Czech Republic.
7
Department of Gynecologic Oncology, Center for Gynecologic Oncology Amsterdam, Antoni van Leeuwenhoek Hospital, The Netherlands.
8
Department of Gynecology and Obstetrics, Innsbruck Medical University, Innsbruck, Austria.
9
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.
10
Cancer Research UK Cambridge Institute, Li Ka Shing Centre, Robinson Way, Cambridge, UK.
11
Abbott Diagnostics, USA.
12
Department of Obstetrics and Gynecology, MCU-FDT Medical Foundation, Philippines.
13
Department of Obstetrics and Gynecology, Institute of Clinical Sciences, Sahlgrenska Cancer Center, University of Gothenburg, Gothenburg, Sweden.
14
Gynecologic Oncology Unit, La Paz University Hospital, Madrid, Spain.
15
Department of Gynecology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.

Abstract

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.

KEYWORDS:

Age; Biomarkers; CA125; CPH-I; Copenhagen Index; HE4; Ovarian cancer; Tumor markers

PMID:
26086566
DOI:
10.1016/j.ygyno.2015.06.021
[Indexed for MEDLINE]

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