Funding
NIH
European Commission
International Agency for Research on Cancer
Danish Cancer Society
Ligue Contre le Cancer
Institut Gustave-Roussy
Mutuelle Générale de l'Education Nationale
INSERM
Deutsche Krebshilfe
Deutsches Krebsforschungszentrum
Federal Ministry of Education and Research
Hellenic Health Foundation
Stavros Niarchos Foundation
AIRC
National Research Council Italy
VWS
Netherlands Cancer Registry
LK Research Funds
Dutch Prevention Funds
Dutch ZON
World Cancer Research Fund
Statistics Netherlands
ERC
NordForsk
Nordic Centre of Excellence programme on Food, Nutrition, and Health
Health Research Fund
Regional Governments of Andalucía, Asturias, Basque Country, Murcia
ISCIII
Swedish Cancer Society
Swedish Scientific Council
Regional Government of Skå ne and Västerbotten
Cancer Research UK
Medical Research Council
ARTICLE ABSTRACT
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
