Serum mesothelin for diagnosing malignant pleural mesothelioma : an individual patient data meta-analysis

Hollevoet, Kevin; Reitsma, Johannes B.; Creaney, Jenette; van Meerbeeck, Jan P.; et al.

doi:10.1200/JCO.2011.39.6671

Title

Serum mesothelin for diagnosing malignant pleural mesothelioma : an individual patient data meta-analysis

Author

Hollevoet, Kevin

Reitsma, Johannes B.

Creaney, Jenette

van Meerbeeck, Jan P.

et al.

Abstract

Purpose Mesothelin is currently considered the best available serum biomarker of malignant pleural mesothelioma. To examine the diagnostic accuracy and use of serum mesothelin in early diagnosis, we performed an individual patient data (IPD) meta-analysis. Methods The literature search identified 16 diagnostic studies of serum mesothelin, measured with the Mesomark enzyme-linked immunosorbent assay. IPD of 4,491 individuals were collected, including several control groups and 1,026 patients with malignant pleural mesothelioma. Mesothelin levels were standardized for between-study differences and age, after which the diagnostic accuracy and the factors affecting it were examined with receiver operating characteristic (ROC) regression analysis. Results At a common diagnostic threshold of 2.00 nmol/L, the sensitivities and specificities of mesothelin in the different studies ranged widely from 19% to 68% and 88% to 100%, respectively. This heterogeneity can be explained by differences in study population, because type of control group, mesothelioma stage, and histologic subtype significantly affected the diagnostic accuracy. The use of mesothelin in early diagnosis was evaluated by differentiating 217 patients with stage I or II epithelioid and biphasic mesothelioma from 1,612 symptomatic or high-risk controls. The resulting area under the ROC curve was 0.77 (95% CI, 0.73 to 0.81). At 95% specificity, mesothelin displayed a sensitivity of 32% (95% CI, 26% to 40%). Conclusion In patients suspected of having mesothelioma, a positive blood test for mesothelin at a high-specificity threshold is a strong incentive to urge further diagnostic steps. However, the poor sensitivity of mesothelin clearly limits its added value to early diagnosis and emphasizes the need for further biomarker research. J Clin Oncol 30: 1541-1549. (C) 2012 by American Society of Clinical Oncology

Language

English

Source (journal)

Journal of clinical oncology. - New York

Publication

New York : 2012

ISSN

0732-183X

DOI

10.1200/JCO.2011.39.6671

Volume/pages

30 :13 (2012) , p. 1541-1549