A prospective evaluation of early detection biomarkers for ovarian cancer in the European EPIC cohort

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 KroghElisabetta 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 Cramer, Rudolf Kaaks

Research output: Contribution to journalArticleAcademicpeer-review


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 (EPIC) 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. Additionally, 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 six months of diagnosis for CA125 (C-statistic=0.92), 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.

Original languageEnglish
Pages (from-to)4664-4675
JournalClinical Cancer Research
Issue number18
Publication statusPublished - Sept 2016


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