A prospective evaluation of early detection biomarkers for ovarian cancer in EPIC cohort - open access

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 April 8, 2016

.... Within the first 12 months after blood donation, for all markers except CA15.3 the ability to predict future cancer diagnosis was clearly stronger for advanced tumors (stage II and III/IV) and relatively weak for stage I tumors (Supplementary Figure 1), and this heterogeneity was statistically significant for CA125 and HE4 (phet < 0.05; Table 2). Regarding tumor histology, CA125, HE4 and CA72.4 showed fairly strong discrimination of serous ovarian cancer patients from their matched controls, especially within short lag-times after blood donation (Supplementary Table S2); for the other histologic subtypes, the numbers of patients were too small to obtain reliable estimates.....

 Discussion
In our evaluation of four potential ovarian cancer screening biomarkers measured in prospectively collected samples from women with ovarian cancer and matched controls in the EPIC cohort, we observed the best sensitivity and specificity for CA125, followed by HE4, CA72.4, and finally CA15.3. The ability of these biomarkers to distinguish cases from controls declined with increasing time between blood draw and diagnosis, as well as with earlier stage at diagnosis. These observations suggest that, generally, these markers are best at identifying advanced disease close to diagnosis, but their ability to detect early disease that is amenable to interventions that can improve survival may be limited. Addition of a previously established risk prediction model did not improve the performance of markers in women who went on to develop clinically manifest ovarian cancer less than three years in advance of diagnosis. By contrast, adding CA125 (but not CA15.3) to the risk prediction model did slightly improve the longer-term
prediction of ovarian cancer occurrence over a time interval of about 3 to 6 years after blood donation.....

(Results)  Combining CA125 with HE4 and further markers modestly improved discrimination. Our study confirms CA125 as the single best marker for the early detection of invasive epithelial ovarian cancer.