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

Abstract

Background: The role of combinations of tumor markers such as carcinoembryonic antigen (CEA), carbohydrate antigens (CA) 125, 15-3, and 19-9, and CYFRA 21-1 (a fragment of cytokeratin 19) in diagnosing malignant pleural effusion (MPE) has not been clearly established. Objectives: This meta-analysis was performed to establish the overall diagnostic accuracies of combinations of these pleural fluid tumor markers for MPE. Methods: The PubMed, Ovid, Embase, Web of Science, and Cochrane bibliographic databases were searched. Sensitivity, specificity, and other measures of the accuracy of combinations of pleural CEA, CA 125, CA 15-3, CA 19-9, and CYFRA 21-1 in the diagnosis of MPE were pooled after a systematic review of English-language studies. Results: Twenty studies met the inclusion criteria. For pleural fluid tumor marker combinations including more than 3 studies, the summary estimates of the sensitivity/specificity for diagnosing MPE were as follows: CEA + CA 125, 0.65/0.98; CEA + CA 15-3, 0.64/0.98; CEA + CA 19-9, 0.58/0.98; CEA + CYFRA 21-1, 0.82/0.92; and CA 15-3 + CYFRA 21-1, 0.88/0.94. Conclusions: In patients with undiagnosed pleural effusion, the combinations of positive pleural CEA + CA 15-3 and CEA + CA 19-9 are highly suspicious for pleural malignancy, but the sensitivity of these tests is poor. Therefore, their routine role in the diagnostic algorithm of these patients is questionable, and management decisions should depend on positive cytological or biopsy results from the pleura.

A machine learning evolutionary algorithm-based formula to assess tumor markers and predict lung cancer in cytologically negative pleural effusions

“…Our results suggest that the measurement of CYFRA21-1 and CEA levels in lung cancer-associated MPE yields the highest diagnostic accuracy. Indeed, classification rules that can be extracted by the proposed formula are in good agreement with the a priori knowledge about the considered tumor markers (Yang et al 2017).…”

“…Most investigated tumor markers, both in serum and pleural fluid, include carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), carbohydrate antigen 125 (CA125), and M2-Pyruvate-kinase (M2PK) with reported sensitivities varying from 20 to 98% (Gu et al 2007;Shitrit et al 2005;Elia et al 2008;Yang et al 2017;Alataş et al 2001).…”

ERS/EACTS statement on the management of malignant pleural effusions

“…primary pleural malignancy versus metastatic disease. Disease-specific immunochemical markers are summarised in table 2 [230][231][232][233][234].…”

Diagnostic Accuracy of Interleukin-27 between Tuberculous Pleural Effusion and Malignant Pleural Effusion: A Meta-Analysis

“…Differential diagnosis of TPE from PE with the other etiologies, especially MPE, is always a diagnostic challenge [2, 3]. In a recent issue of Respiration, Yang et al [4] put forward that the combinations of 2 or more tumor markers are highly specific but insufficiently sensitive for diagnosing MPE. The gold standard of MPE still relies on pathological diagnosis – to find malignant cells in PE or to find pathological changes on pleural biopsy specimen.…”