American Association for Cancer Research
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Evaluation of added discriminatory ability from A Prospective Evaluation of Early Detection Biomarkers for Ovarian Cancer in the European EPIC Cohort

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journal contribution
posted on 2023-03-31, 19:30 authored by Kathryn L. Terry, Helena Schock, Renée T. Fortner, Anika Hüsing, Raina N. Fichorova, Hidemi S. Yamamoto, Allison F. Vitonis, Theron Johnson, Kim Overvad, Anne Tjønneland, Marie-Christine Boutron-Ruault, Sylvie Mesrine, Gianluca Severi, Laure Dossus, Sabina Rinaldi, Heiner Boeing, Vassiliki Benetou, Pagona Lagiou, Antonia Trichopoulou, Vittorio Krogh, Elisabetta Kuhn, Salvatore Panico, H. Bas Bueno-de-Mesquita, N. Charlotte Onland-Moret, Petra H. Peeters, Inger Torhild Gram, Elisabete Weiderpass, Eric J. Duell, Maria-Jose Sanchez, Eva Ardanaz, Nerea Etxezarreta, Carmen Navarro, Annika Idahl, Eva Lundin, Karin Jirström, Jonas Manjer, Nicholas J. Wareham, Kay-Tee Khaw, Karl Smith Byrne, Ruth C. Travis, Marc J. Gunter, Melissa A. Merritt, Elio Riboli, Daniel W. Cramer, Rudolf Kaaks

Evaluation of added discriminatory ability of each biomarker using Net Reclassification Improvement (NRI)



European Commission

International Agency for Research on Cancer

Danish Cancer Society

Ligue Contre le Cancer

Institut Gustave-Roussy

Mutuelle Générale de l'Education Nationale


Deutsche Krebshilfe

Deutsches Krebsforschungszentrum

Federal Ministry of Education and Research

Hellenic Health Foundation

Stavros Niarchos Foundation


National Research Council Italy


Netherlands Cancer Registry

LK Research Funds

Dutch Prevention Funds

Dutch ZON

World Cancer Research Fund

Statistics Netherlands



Nordic Centre of Excellence programme on Food, Nutrition, and Health

Health Research Fund

Regional Governments of Andalucía, Asturias, Basque Country, Murcia


Swedish Cancer Society

Swedish Scientific Council

Regional Government of Skå ne and Västerbotten

Cancer Research UK

Medical Research Council



Purpose: About 60% of ovarian cancers are diagnosed at late stage, when 5-year survival is less than 30% in contrast to 90% for local disease. This has prompted search for early detection biomarkers. For initial testing, specimens taken months or years before ovarian cancer diagnosis are the best source of information to evaluate early detection biomarkers. Here we evaluate the most promising ovarian cancer screening biomarkers in prospectively collected samples from the European Prospective Investigation into Cancer and Nutrition study.Experimental Design: We measured CA125, HE4, CA72.4, and CA15.3 in 810 invasive epithelial ovarian cancer cases and 1,939 controls. We calculated the sensitivity at 95% and 98% specificity as well as area under the receiver operator curve (C-statistic) for each marker individually and in combination. In addition, we evaluated marker performance by stage at diagnosis and time between blood draw and diagnosis.Results: We observed the best discrimination between cases and controls within 6 months of diagnosis for CA125 (C-statistic = 0.92), then HE4 (0.84), CA72.4 (0.77), and CA15.3 (0.73). Marker performance declined with longer time between blood draw and diagnosis and for earlier staged disease. However, assessment of discriminatory ability at early stage was limited by small numbers. Combinations of markers performed modestly, but significantly better than any single marker.Conclusions: CA125 remains the single best marker for the early detection of invasive epithelial ovarian cancer, but can be slightly improved by combining with other markers. Identifying novel markers for ovarian cancer will require studies including larger numbers of early-stage cases. Clin Cancer Res; 22(18); 4664–75. ©2016 AACR.See related commentary by Skates, p. 4542

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