The role of tumour markers such as carbohydrate antigen (CA) 125, CA 15-3, CA 19-9 and CYFRA 21-1 (a fragment of cytokeratin 19) in differentiating malignant pleural effusions (MPE) from benign effusions is not yet clear.

After a systematic review of English language studies, sensitivity, specificity and other measures of accuracy of pleural concentrations of CA 125, CA 15-3, CA 19-9 and CYFRA 21-1 or their combinations in the diagnosis of MPE were pooled using random effects models. Summary receiver operating characteristic curves were used to summarise overall test performance.

Twenty-nine studies met the inclusion criteria for the analysis. The summary estimates of the sensitivity and specificity of these tumour markers were as follows: CA 125, 0.48/0.85; CA 15-3, 0.51/0.96; CA 19-9, 0.25/0.96; CYFRA 21-1, 0.55/0.91 for diagnosing MPE. The estimated summary receiver operating characteristic curves showed that the performance of pleural CA 125 and CA 19-9 measurement in the diagnosis of MPE was limited, whereas that of CA 15-3 and CYFRA 21-1 was better. When two or more of the above four tumour markers were combined, or combined with carcinoembryonic antigen, the sensitivity and specificity were all increased to different extents.

The current evidence does not recommend using one tumour marker alone for the diagnosis of MPE, but the combination of two or more tumour markers seems to be more sensitive. The results of tumour marker assays should be interpreted in parallel with clinical findings and the results of conventional tests.