Preoperative Sensitivity and Specificity for Early-Stage Ovarian Cancer When Combining Cancer Antigen CA-125II, CA 15-3, CA 72-4, and Macrophage Colony-Stimulating Factor Using Mixtures of Multivariate Normal Distributions

Purpose In CA-125–based ovarian cancer screening trials, overall specificity and screening sensitivity of ultrasound after an elevated CA-125 exceeded 99.6% and 70%, respectively, thereby yielding a positive predictive value (PPV) exceeding 10%. However, sensitivity for early-stage disease was only 40%. This study aims to increase preoperative sensitivity for early-stage ovarian cancer while maintaining the annual referral rate to ultrasound at 2% by combining information across CA-125II, CA 15-3, CA 72-4, and macrophage colony-stimulating factor (M-CSF). For direct comparisons between marker panels, all sensitivity results correspond to a 98% fixed first-line specificity (referral rate 2%). Patients and Methods Logistic regression, classification tree, and mixture discriminant analysis (MDA) models were fit to a training data set of preoperative serum measurements (63 patients, 126 healthy controls) from one center. Estimates from the training set applied to an independent validation set (60 stage I to I...