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Clinical Cancer Research
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
This article is featured in Highlights of This Issue, p. 4537