NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.

Cover of What carcinoembryonic antigen level should trigger further investigation during colorectal cancer follow-up? A systematic review and secondary analysis of a randomised controlled trial

What carcinoembryonic antigen level should trigger further investigation during colorectal cancer follow-up? A systematic review and secondary analysis of a randomised controlled trial

Health Technology Assessment, No. 21.22

, , , , , , , and .

Author Information
Southampton (UK): NIHR Journals Library; .


Single CEA tests for triage in follow-up of colorectal cancer generate many false positives and are less clinically useful than CEA trends.



Following primary surgical and adjuvant treatment for colorectal cancer, many patients are routinely followed up with blood carcinoembryonic antigen (CEA) testing.


To determine how the CEA test result should be interpreted to inform the decision to undertake further investigation to detect treatable recurrences.


Two studies were conducted: (1) a Cochrane review of existing studies describing the diagnostic accuracy of blood CEA testing for detecting colorectal recurrence; and (2) a secondary analysis of data from the two arms of the FACS (Follow-up After Colorectal Surgery) trial in which CEA testing was carried out.

Setting and participants:

The secondary analysis was based on data from 582 patients recruited into the FACS trial between 2003 and 2009 from 39 NHS hospitals in England with access to high-volume services offering surgical treatment of metastatic recurrence and followed up for 5 years. CEA testing was undertaken in general practice.


In the systematic review we identified 52 studies for meta-analysis, including in aggregate 9717 participants (median study sample size 139, interquartile range 72–247). Pooled sensitivity at the most commonly recommended threshold in national guidelines of 5 µg/l was 71% [95% confidence interval (CI) 64% to 76%] and specificity was 88% (95% CI 84% to 92%). In the secondary analysis of FACS data, the diagnostic accuracy of a single CEA test was less than was suggested by the review [area under the receiver operating characteristic curve (AUC) 0.74, 95% CI 0.68 to 0.80]. At the commonly recommended threshold of 5 µg/l, sensitivity was estimated as 50.0% (95% CI 40.1% to 59.9%) and lead time as about 3 months. About four in 10 patients without a recurrence will have at least one false alarm and six out of 10 tests will be false alarms (some patients will have multiple false alarms, particularly smokers). Making decisions to further investigate based on the trend in serial CEA measurements is better (AUC for positive trend 0.85, 95% CI 0.78 to 0.91), but to maintain approximately 70% sensitivity with 90% specificity it is necessary to increase the frequency of testing in year 1 and to apply a reducing threshold for investigation as measurements accrue.


The reference standards were imperfect and the main analysis was subject to work-up bias and had limited statistical precision and no external validation.


The results suggest that (1) CEA testing should not be used alone as a triage test; (2) in year 1, testing frequency should be increased (to monthly for 3 months and then every 2 months); (3) the threshold for investigating a single test result should be raised to 10 µg/l; (4) after the second CEA test, decisions to investigate further should be made on the basis of the trend in CEA levels; (5) the optimal threshold for investigating the CEA trend falls over time; and (6) continuing smokers should not be monitored with CEA testing. Further research is needed to explore the operational feasibility of monitoring the trend in CEA levels and to externally validate the proposed thresholds for further investigation.

Study registration:

This study is registered as PROSPERO CRD42015019327 and Current Controlled Trials ISRCTN93652154.


The main FACS trial and this substudy were funded by the National Institute for Health Research Health Technology Assessment programme.


About the Series

Health Technology Assessment
ISSN (Print): 1366-5278
ISSN (Electronic): 2046-4924

Article history

The research reported in this issue of the journal was funded by the HTA programme as project number 11/136/81. The contractual start date was in March 2013. The draft report began editorial review in March 2016 and was accepted for publication in August 2016. The authors have been wholly responsible for all data collection, analysis and interpretation, and for writing up their work. The HTA editors and publisher have tried to ensure the accuracy of the authors’ report and would like to thank the reviewers for their constructive comments on the draft document. However, they do not accept liability for damages or losses arising from material published in this report.

Declared competing interests of authors


Last reviewed: March 2016; Accepted: August 2016.

Copyright © Queen’s Printer and Controller of HMSO 2017. This work was produced by Shinkins et al. under the terms of a commissioning contract issued by the Secretary of State for Health. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK.

Included under terms of UK Non-commercial Government License.

Bookshelf ID: NBK426112DOI: 10.3310/hta21220


  • PubReader
  • Print View
  • Cite this Page
  • PDF version of this title (2.8M)
  • Disable Glossary Links

Other titles in this collection

Related information

Similar articles in PubMed

See reviews...See all...

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...