A Prospective Study Consortium for the Discovery and Validation of Early Detection Markers for Ovarian Cancer ("PREDICT") - Baseline findings for CA125

Abstract

Abstract

Purpose: Epithelial ovarian cancer (EOC) is a lethal malignancy. CA125, the “best” available marker for detecting EOC, has insufficient sensitivity and specificity for earlier-stage disease and is not a meaningful screening tool, motivating the search for further biomarkers. Cancer biomarker discovery is enhanced by “omics” technologies. Discovery studies for EOC biomarkers should be conducted in pre-diagnosis blood samples from prospective cohorts to maximize likelihood of identifying markers that can detect disease before usual diagnosis and in earlier disease stage, while reducing methodologic biases. Experimental

Design: Individual cohorts with pre-diagnosis blood samples have insufficient sample size for such studies. thus, we established “PREDICT” (“Prospective Early Detection Consortium for Ovarian Cancer")—a collaboration of nine prospective studies—to assemble a sufficient number of EOC cases with blood samples collected ≤18 months before diagnosis plus controls. The 457 cases and 1,687 controls have circulating CA125 measured using a clinical assay.

Results: The discrimination capacity for single CA125 measurements in samples collected <6 months prior to diagnosis was high (area under the curve (AUC), PREDICT overall=0.92; range across cohorts of non-pregnant individuals=0.89–0.98), and declined with extended time between blood collection and diagnosis. Between-cohort variability in CA125 levels and predictive performance was observed.

Conclusions: Ongoing investigations in PREDICT are evaluating the early detection potential of tumor-associated autoantibodies and microRNAs, using CA125 as a benchmark. PREDICT is a well-characterized resource for identifying and validating detection markers for EOC that may then be used in multi-modal screening, as a complement to CA125 and combined with imaging.