Clinical diagnostic utility of CA 15-3 for the diagnosis of malignant pleural effusion: A meta-analysis

Malignant pleural effusion (MPE) is one of the most common pleura-associated conditions observed in clinical practice. The development of MPE usually defines advanced cancer with a poor prognosis. Carbohydrate antigen 15-3 (CA 15-3), as an effective pleural fluid biomarker, has been an object of ongoing research in the detection of MPE. The aim of this meta-analysis was to establish the overall diagnostic accuracy of the measurement of pleural CA 15-3 for diagnosing MPE. The databases Medline (using PubMed as the search engine), Embase, Ovid, Web of Science and Cochrane database (up to December 2013) were searched to identify relevant studies. No lower date limit was applied. All literature published in English was reviewed. Sensitivity, specificity, likelihood ratio and diagnostic odds ratio (DOR) were pooled using a random-effect model. Summary receiver operating characteristic (SROC) curve analysis was conducted to evaluate the overall diagnostic value. The methodological quality was assessed in line with the Quality Assessment for Studies of Diagnostic Accuracy statement. Twenty-one studies with a total of 2,861 cases were included in present meta-analysis. The sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR) and DOR of CA 15-3 in the diagnosis of MPE were 0.58 [95% confidence interval (CI), 0.56-0.61], 0.91 (95% CI, 0.90-0.93), 8.93 (95% CI, 4.45-17.93), 0.46 (95% CI, 0.37-0.56) and 24.89 (95% CI, 10.39-59.63), respectively. In addition, the area under the curve (AUC) was 0.84. In conclusion, due to the significantly high specificity of pleural CA 15-3 in detecting MPE, it may play a pivotal role in screening to identify patients who may benefit from further invasive pathologic examination, particularly in those presenting clinical manifestations of MPE but with negative cytological findings of the pleural fluid. However, ruling out MPE by testing CA15-3 alone is not recommended due to its limited sensitivity, and it is recommended that the results of CA15-3 assays are interpreted in parallel with conventional test results and other clinical findings.