Utility of CEA and CA 15-3 measurements in non-purulent pleural exudates in the diagnosis of malignancy: A single-center experience

Our plain-English summary of Utility of CEA and CA 15-3 measurements in non-purulent pleural exudates in the diagnosis of malignancy: A single-center experience, by J.M. Porcel, C. Civit, A. Esquerda, et al (Archivos de Bronconeumología, 2017).

The study

• Authors: J.M. Porcel, C. Civit, A. Esquerda, A. Salud, S. Bielsa
• Journal: Archivos de Bronconeumología
• Published: 2017;53(8):427-431
• Language: Spanish
• Cited by: 28 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Objective: To establish the diagnostic accuracy of pleural fluid (PF) CEA and CA 15-3 in identifying malignancy, and to determine the additional value of these markers in patients with malignant pleural effusions (MPEs) with false negative results from cytological fluid examination.

Methods: PF concentrations of CEA and/or CA 15-3 were determined in 1,575 patients with non-purulent exudates, 549 of whom had confirmed MPEs, 284 probable MPEs, and 742 benign effusions. Tumor marker cut-off points were set to ensure 100% specificity for malignant effusion.

Results: The 41, 40 and 60% of MPE patients had high PF levels of CEA (>45ng/mL), CA 15-3 (>77 UI/l) or both, respectively. These percentages were 30, 19 and 41% in MPEs with positive pleural biopsy and negative PF cytology; and 24, 13 and 35% in clinical MPEs without histocytological confirmation. Tumor markers were of no value in lymphomas and mesotheliomas. The area-under-the-curve for CEA was 0.819 (95% CI: 0,793-0,845) and for CA 15-3, it was 0.822 (95% CI: 0,796-0,847). The use of tumor markers compared to cytology alone, increased the diagnosis of malignancy by 14%.

Conclusions: Measurements of PF CEA and CA 15-3 may complement pleural cytology in the identification of MPEs.

Copyright © 2017 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.

In plain English

This single-center study in Lleida, Spain, reviewed 1,575 patients with non-purulent pleural exudates (fluid around the lungs) examined from 2003 to 2016. Of these, 549 had confirmed malignant effusions, 284 probably malignant, and 742 benign. The study did not look at asbestos exposure. It measured pleural fluid CEA and CA 15-3 using cut-offs no benign effusion exceeded: above 45 ng/mL and above 77 UI/mL respectively. Among confirmed malignant effusions, CEA was high in 226 of 549 (41%, 95% CI 37-45), CA 15-3 in 202 of 506 (40%, 95% CI 36-44), and at least one marker in 317 of 527 (60%, 95% CI 56-64). Among the 17 mesotheliomas, CEA was high in 0 and at least one marker in 3 (18%). The authors called the markers practically useless in lymphomas and mesotheliomas. Overall, cytology alone detected 60% (95% CI 57-64) of malignant effusions and cytology plus markers 74% (95% CI 71-77). The authors concluded the markers add useful information, but that patients who are candidates for active cancer treatment still need cell or tissue confirmation. They noted the study was retrospective and single-center.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Retrospective review of consecutive patients at a single center (diagnostic accuracy study of pleural fluid tumor markers)
• Who was studied: Patients at the Pleural Medicine Unit of Hospital Universitario Arnau de Vilanova, Lleida, Spain, August 2003 to August 2016. Of 2,580 patients with pleural fluid CEA or CA 15-3 requested, 191 empyemas and 814 transudates were excluded. That left 1,575 non-purulent exudates: 549 confirmed malignant, 284 probably malignant, 742 benign. The confirmed malignant group included 17 mesotheliomas. Pleural mesothelioma always required histological confirmation.
• Exposure: No asbestos or other environmental exposure was studied. The study evaluated pleural fluid CEA and CA 15-3, measured by electrochemiluminescence on a Roche Elecsys analyzer, as tests for identifying malignancy.
• Main results:
  • Cut-offs with 100% specificity were CEA above 45 ng/mL and CA 15-3 above 77 UI/mL. In confirmed malignant effusions, the cut-off was exceeded by CEA in 41% (95% CI 37-45; 226 of 549) and by CA 15-3 in 40% (95% CI 36-44; 202 of 506). At least one marker was high in 60% (95% CI 56-64; 317 of 527).
  • A high marker was definitive for malignancy (infinite positive likelihood ratios). A normal marker did not substantially change the probability of cancer: negative likelihood ratios were 0.59 for CEA and 0.60 for CA 15-3.
  • The area under the curve was 0.819 (95% CI 0.793-0.845) for CEA and 0.822 (95% CI 0.796-0.847) for CA 15-3.
  • In malignant effusions proven by pleural biopsy but with negative fluid cytology, CEA, CA 15-3 or either marker correctly classified 30% (14 of 46), 19% (8 of 42) and 41% (18 of 44) as malignant. In probably malignant effusions the figures were 24% (67 of 283), 13% (32 of 253) and 35% (92 of 261). These did not differ significantly from the biopsy-proven group.
  • In the 17 mesotheliomas, CEA was high in 0 of 17, CA 15-3 in 3 of 17 (18%), and either marker in 3 of 17 (18%). In lymphomas, either marker was high in 1 of 33 (3%). The authors described the combined markers as practically useless in lymphomas and mesotheliomas.
  • Sensitivity varied by primary tumor. CA 15-3 alone reached 79% in ovarian tumors. Either marker reached 83% in gastrointestinal adenocarcinomas, 81% in ovarian tumors and 73% in lung adenocarcinomas.
  • The article reports overall sensitivity (without stating which malignant groups the figure covers) of 60% (95% CI 57-64) for pleural fluid cytology and 49% (95% CI 46-52) for either marker. Counting a positive result on either test, sensitivity rose to 74% (95% CI 71-77).
• The authors' conclusion: The authors concluded that pleural fluid CEA and CA 15-3, with 100% specific cut-offs, add clinical information by increasing the ability to identify malignant effusions. They added that this does not remove the need for cytological or tissue confirmation in patients who are candidates for active cancer treatment.
• Limitations the authors state:
  • The study was a retrospective, single-center evaluation, and its results should be validated in independent populations at other centers.
  • Some paramalignant effusions (not directly caused by tumor invasion of the pleura) may have been wrongly placed in the probably malignant group, which was not confirmed by pleuroscopy.
  • Choosing 100% specific cut-offs lowers the sensitivity of any test. Here about 40% of malignant effusions exceeded the cut-off for each marker alone.

Topics

Medical terms in this study, explained in our Lexicon: Exudate, Pleural Effusion, Tumor Marker, Pleural Biopsy, Cytology, Mesothelioma.

Related studies

• Success rate of medical thoracoscopy and talc pleurodesis in malignant pleurisy: A single-centre experience — J. Leemans, C. Dooms, et al. (2018)
• Evolution of locoregional treatment for peritoneal carcinomatosis: single-center experience of 308 procedures of cytoreductive surgery and perioperative intraperitoneal chemotherapy — T.C. Chua, W. Liauw, et al. (2011)
• A multidisciplinary approach for the diagnosis of benign asbestos pleural effusion: a single-center experience — W. Luo, Y. Zeng, et al. (2020)
• Overexpression and altered glycosylation of MUC1 in malignant mesothelioma — J. Creaney, A. Segal, et al. (2008)
• Practical utility of insulin-like growth factor II mRNA-binding protein 3, glucose transporter 1, and epithelial membrane antigen for distinguishing malignant mesotheliomas from benign mesothelial proliferations — S. Chang, M.H. Oh, et al. (2014)
• Identifying Thoracic Malignancies Through Pleural Fluid Biomarkers: A Predictive Multivariate Model — J.M. Porcel, A. Esquerda, et al. (2016)

Browse more research in Archivos de Bronconeumología, or return to medical research.