Phase II biomarker trial of a multimarker diagnostic for ovarian cancer

The primary hypothesis to be tested in this study was that the diagnostic performance (as assessed by the area under the receiver operator characteristic curve, AUC) of a multianalyte panel to correctly identify women with ovarian cancer was significantly greater than that for CA-125 alone. A retrospective, case-control study (phase II biomarker trial) was conducted that involved 362 plasma samples obtained from women with ovarian cancer (n = 150) and healthy controls (n = 212). A multivariate classification model was developed that incorporated five biomarkers of ovarian cancer, CA-125; C-reactive protein (CRP); serum amyloid A (SAA); interleukin 6 (IL-6); and interleukin 8 (IL-8) from a modelling cohort (n = 179). The performance of the model was evaluated using an independent validation cohort (n = 183) and compared with of CA-125 alone. The AUC for the biomarker panel was significantly greater than the AUC for CA-125 alone for a validation cohort (p < 0.01) and an early stage disease cohort (i.e. Stages I and II; p < 0.01). At a threshold of 0.3, the sensitivity and specificity of the multianalyte panel were 94.1 and 91.3%, respectively, for the validation cohort and 92.3 and 91.3%, respectively for an early stage disease cohort. The use of a panel of plasma biomarkers for the identification of women with ovarian cancer delivers a significant increase in diagnostic performance when compared to the performance of CA-125 alone.