Diagnostic accuracy of tumor markers for malignant pleural effusion: a derivation and validation study

Abstract

Background: The utility of tumor markers (TMs) for differentiating malignant pleural effusion (MPE) from benign pleural effusion (BPE) has been a subject of controversy. The majority of published studies are single center designed and lack validation. We performed a derivation and validation study in China to evaluate the diagnostic value of carcinoembryonic antigen (CEA) as well as carbohydrate antigen (CA) 15-3, CA 19-9 and CA 125 to differentiate between MPE and BPE. Methods: Three hundred and twenty seven pleural effusion (PE) and paired serum samples were collected from consecutive patients with MPE or BPE in Beijing (174 patients, derivation) and Wuhan (153 patients, validation) during the same period. The concentrations of four TMs were tested using chemiluminescent microparticle immunoassay technology. The performance of the TMs was analyzed by standard receiver operating characteristic (ROC) curves. Results: The levels of four TMs were significantly higher in MPE than in BPE and the corresponding serum. The concentrations of CEA and CA 15-3 were more stable than the concentrations of CA 125 and CA 19-9. CEA was the best single marker for discriminating MPE from BPE. With a specificity of 100% in the total population, the highest sensitivity (37.8%) using serum was found in CEA. In addition, CEA presented 19.8% sensitivity in PE and 18.0% sensitivity in the ∆(PE-serum). For CA 15-3, the sensitivity was 32.4% in PE, 15.3% in the PE/serum ratio and 25.2% in the ∆(PE-serum).Conclusions: CEA and CA 15-3 rather than CA 125 and CA 19-9 are more reliable to differentiate between MPE and BPE. The use of the ∆(PE-serum) value in TMs, such as CEA and CA 15-3, may improve the sensitivity and specificity of the diagnosis etiology of PE.Keywords: Pleural effusion (PE); tumor marker (TM); diagnosis; carcinoembryonic antigen (CEA); CA 125; CA Submitted Jan 13, 2017. Accepted for publication Aug 15, 2017Aug 15, . doi: 10.21037/jtd.2017 View this article at: http://dx.doi.org/10.21037/jtd.2017.11.62 5221 Journal of Thoracic Disease, Vol 9, No 12 December 2017 © Journal of Thoracic Disease. All rights reserved.J Thorac Dis 2017;9(12):5220-5229 jtd.amegroups.com IntroductionMalignant pleural effusion (MPE) is frequently observed in some malignancies, implying systemic spread of cancer and reduction of life expectancy and quality (1). The initial diagnostic approaches to differentiation between benign pleural effusions (BPEs) and MPEs include thoracocentesis and cytological, histological and biochemical examinations; however, the sensitivity of these non-invasive techniques is only 40-70% (2). Many studies have investigated the usefulness of a number of tumor markers (TMs), including carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 125, CA 15-3, and CA 19-9, in pleural fluid for the diagnosis of MPE (3). Our previous meta-analyses indicated that current evidence does not recommend using a single TM for the diagnosis of MPE; a combination of two or more TMs seemingly is more sensitive (4,5). We, along with oth...

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