Utility of a Multi-Marker Panel with Ultrasound for Enhanced Classification of Adnexal Mass.

Pre-surgical clinical assessment of an adnexal mass typically relies on transvaginal ultrasound for comprehensive morphological assessment, with further support provided by biomarker measurements and clinical evaluation. Whilst effective for masses that are obviously benign or malignant, a large proportion of masses remain sonographically indeterminate at surgical referral. As a consequence, post-surgical diagnoses of benign disease can outnumber malignancies up to 9-fold, while less than 50% of cancer cases receive a primary referral to a gynecological oncology specialist. We recently described a blood biomarker signature (multi-marker panel-MMP) that differentiated patients with benign from malignant ovarian disease with high accuracy. In this study, we have examined the use of the MMP, both individually and in combination with transvaginal ultrasound, as an alternative tool to CA-125 for enhanced decision making in the pre-surgical referral process.

ReClassification of Patients with Ambiguous CA125 for Optimised Pre-Surgical Triage.

Pre-surgical clinical assessment of an adnexal mass is a complex process, and ideally requires accurate and rapid identification of disease status. Gold standard biomarker CA125 is extensively used off-label for this purpose; however its performance is typically inadequate, particularly for the detection of early stage disease and discrimination between benign versus malignant status. We recently described a multi-marker panel (MMP) and associated risk index for the differentiation of benign from malignant ovarian disease. In this study we applied a net reclassification approach to assess the use of MMP index to rescue those cases where low CA125 incorrectly excludes cancer diagnoses, or where benign disease is incorrectly assessed as "high risk" due to elevated CA125. Reclassification of such patients is of significant value to assist in the timely and accurate referral for patients where CA125 titer is uninformative.

A Novel Predictive Multi-Marker Test for the Pre-Surgical Identification of Ovarian Cancer.

Ovarian cancer remains the most lethal of gynecological malignancies, with the 5-year survival below 50%. Currently there is no simple and effective pre-surgical diagnosis or triage for patients with malignancy, particularly those with early-stage or low-volume tumors. Recently we discovered that CXCL10 can be processed to an inactive form in ovarian cancers and that its measurement has diagnostic significance. In this study we evaluated the addition of processed CXCL10 to a biomarker panel for the discrimination of benign from malignant disease. Multiple biomarkers were measured in retrospectively collected plasma samples (n = 334) from patients diagnosed with benign or malignant disease, and a classifier model was developed using CA125, HE4, Il6 and CXCL10 (active and total). The model provided 95% sensitivity/95% specificity for discrimination of benign from malignant disease. Positive predictive performance exceeded that of "gold standard" scoring systems including CA125, RMI and ROMA% and was independent of menopausal status. In addition, 80% of stage I-II cancers in the cohort were correctly identified using the multi-marker scoring system. Our data suggest the multi-marker panel and associated scoring algorithm provides a useful measurement to assist in pre-surgical diagnosis and triage of patients with suspected ovarian cancer.