Performance of a multianalyte test as an aid for the diagnosis of ovarian cancer in symptomatic women

Abstract

BackgroundConcomitant with the development of in vitro diagnostic multivariate index assays (IVDMIAs) to improve the diagnostic efficiency of ovarian cancer detection is the need to identify appropriate biostatistical approaches to assess improvements in risk predication. In this study, we assessed the utility of three different approaches for comparing diagnostic efficiency of an ovarian cancer multivariate assay in a retrospective case - control phase 2 biomarker trial. The control cohort included both disease-free women and women with benign gynecological conditions to more accurately reflect the target population of symptomatic women.MethodsThe study cohort comprised plasma samples from 244 healthy controls, 223 women with benign gynecological conditions, 53 borderline ovarian cancer cases and 222 women with malignant epithelial ovarian cancer. A multivariate classification model was developed that incorporated plasma concentrations of CA125, C-reactive protein (CRP), serum amyloid-A (SAA), interleukin-6 (IL6) and interleukin-8 (IL8) that were measured using in vitro diagnostics assays on medical device approved clinical analysers. The posterior probability values derived from the implemented algorithm were used for comparisons of the diagnostic performance between the multianalyte panel and CA125 using multiple methods; area under the curve (AUC) of the receiver operating characteristics curve, integrated discrimination improvement (IDI) and net reclassification improvement (NRI).ResultsEach of the biomarkers displayed significantly elevated plasma concentrations in malignant ovarian cancer patients compared with either benign or control subjects. For the discrimination of borderline and malignant ovarian cancer from control and benign subjects, the multivariate classification model showed a significantly greater AUC than that for CA125 alone (88.4% versus 84.3%, respectively, p < 0.001). At a posterior probability threshold of 0.5, the IVDMIA delivered a specificity of 92.3% and a sensitivity of 76.4%. When set at a specificity of 95%, the multimarker diagnostic delivered a sensitivity of 69.5% compared with 62.5% for CA125. Enhanced diagnostic performance of the IVDMIA over the use of CA125 alone was confirmed statistically by alternative comparisons using IDI and NRI.ConclusionsThis study confirms in an independent sample set that a blood-based multianalyte assay has significant advantages over CA125 for distinguishing symptomatic women with borderline and malignant ovarian cancer from controls or those with benign disease.

Association between serum amyloid A levels and cancers: a systematic review and meta-analysis

“…The result of meta-analysis of 20 studies with 3682 patients and 2424 healthy individuals were consistent with the findings of Zhang et al ,14 Cho et al ,15 Wang et al ,16 Autelitano et al ,20 Cocco et al ,21 Wang et al 30 and Edgell et al ,31 showing the strong relationship between SAA levels and cancers. Furthermore, these findings indicated that high SAA levels were certainly correlated with the occurrence and development of cancers.…”

“…There were 14 articles with high methodological quality, including the studies of Zhang et al ,14 Cho et al ,15 Wang et al ,16 Toriola et al ,19 Autelitano et al ,20 Cocco et al ,21 Wood et al ,22 Kanoh et al ,23 Benson et al ,24 Kimura et al ,25 Khan et al ,26 Chan et al ,27 Dai et al 28 and Liu et al 29. The studies of Cocco et al ,13 Wang et al ,30 Edgell et al ,31 Kim et al ,32 Sung et al 33 and Biran et al 34 had low methodological quality.…”

Comparison of the Diagnostic Performances of CA125 and Multiple Marker Combinations for Early Diagnosis of Ovarian Cancer

“…Each of biomarkers displayed significantly elevated serum concentrations in ovarian cancer patient compared with either benign [9]. …”

“…CA125 is most widely used serum biomarker for diagnose for ovarian cancer [8]. CA125 was elevated in only 50% of stage I ovarian cancer cases and in 69% of ovarian tumours while being far more prominently expressed in patients with late stage serous tumours [9]. Thus, CA125 has low sensitivity in early-stage disease and additional ultrasonography or combinations of other markers are required [9][10][11].…”

“…Thus, CA125 has low sensitivity in early-stage disease and additional ultrasonography or combinations of other markers are required [9][10][11]. In recent years, a number of studies have confirmed that combinations of CA125 and other biomarkers provided improved diagnostic performance for early-stage ovarian cancer [5][6][7][9][10][11].…”