Diagnostic value of tumor antigens in malignant pleural effusion: a meta-analysis

Abstract

The diagnostic value of tumor markers, CEA, CA 15-3, CA 19-9, CA 125, CYFRA, and NSE in pleural fluid to differentiate between benign and malignant pleural effusion (MPE) has not yet been clearly established. A review of English language studies using human subjects was performed. Sensitivity and specificity values of the chosen tumor markers were pooled using a random effects model to generate hierarchical summary receiver-operator curves to determine the diagnostic performance of each tumor marker. A total of 49 studies were included in the final analysis. Pooled sensitivity and specificity values for chosen tumor markers for diagnosing MPE are as follows: CEA, 0.549/0.962; CA 15-3, 0.507/0.983; CA 19-9, 0.376/0.980; CA 125, 0.575/0.928; CYFRA, 0.625/0.932; NSE, 0.613/0.884. The use of individual tumor markers in diagnosing MPE has many benefits (cost, invasiveness, etc.). While these tumor markers exhibit high specificity, the low sensitivity of each marker limits the diagnostic value. We conclude that tumor markers used individually are of insufficient diagnostic accuracy for clinical use. Tumor markers used in various combinations or from serum may have some potential worth further investigation.

Diagnostic Accuracy of Combinations of Tumor Markers for Malignant Pleural Effusion: An Updated Meta-Analysis

“…The AUC is currently considered to be the standard method for assessing the accuracy of distribution models. The AUCs of CEA + CA 125, CEA + CA 15-3, CEA + CA 19-9, CEA + CYFRA 21-1, and CA 15-3 + CYFRA 21-1 were 0.86, 0.88, 0.96, 0.95, and 0.98, respectively, which was much higher than the values of the individual tumor markers (CEA, 0.81; CA 15-3, 0.78; CA 19-9, 0.91; CA 125, 0.79; CYFRA 21-1, 0.84) [7] . The maximum joint sensitivity and specificity -the point of intersection of the SROC curves [34] -of these combinations was 0.79, 0.81, 0.90, 0.89, and 0.95, respectively.…”

“…The trade-off between sensitivity and specificity has significant clinical implications for the use of combined tumor markers in differentiating MPE from non-MPE. The sensitivity is higher than that of single markers (CEA, 0.549; CA 15-3, 0.507; CA 19-9, 0.376; CA 125, 0.575; CYFRA 21-1, 0.625) [7] , but not by a statistically significant margin. The low sensitivity of any of the tumor marker combinations restricts the clinical applicability of these tests dramatically.…”

“…The value of a DOR ranges from 0 to infinity, with a higher value indicating a better discriminatory test performance (higher accuracy [7] , also indicating that measurement of combined tumor markers would be more helpful than testing tumor markers individually.…”

“…Our results showed that using 1 tumor marker alone for the diagnosis of MPE cannot be recommended, but the combination of 2 or more tumor markers seems to be more sensitive [6] . More recently, Nguyen et al [7] performed a meta-analysis showing that the summary estimates of the sensitivity and specificity of pleural CEA, CA 15-3, CA 19-9, CA 125, and CYFRA 21-1 were as follows: CEA, 0.549 and 0.962; CA 15-3, 0.507 and 0.983; CA 19-9, 0.376 and 0.980; CA 125, 0.575 and 0.928; and CYFRA 21-1, 0.625 and 0.932. These figures were not as high as expected.…”

Thymidine kinase 1 concentration in pleural effusion is a diagnostic marker and survival predictor for malignant pleural effusion

“…Biomarkers for the diagnosis and survival evaluation in pleural effusion have been extensively studied, and most soluble protein biomarkers are more effective when measured in pleural effusion than in serum . The use of pleural biomarkers offers a cost‐effective and minimally invasive method for MPE management …”