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Serum carcinoembryonic antigen trends for diagnosing colorectal cancer recurrence in the FACS randomized clinical trial

Serum carcinoembryonic antigen trends for diagnosing colorectal cancer recurrence in the FACS randomized clinical trial
Serum carcinoembryonic antigen trends for diagnosing colorectal cancer recurrence in the FACS randomized clinical trial

Background: Most guidelines recommend that patients who have undergone curative resection for primary colorectal cancer are followed up for 5 years with regular blood carcinoembryonic antigen (CEA) tests to trigger further investigation for recurrence. However, CEA may miss recurrences, or patients may have false alarms and undergo unnecessary investigation. 

Methods: The diagnostic accuracy of trends in CEA measurements for recurrent colorectal cancer, taken as part of the FACS (Follow-up After Colorectal Surgery) trial (2003-2014), were analysed. Investigation to detect recurrence was triggered by clinical symptoms, scheduled CT or colonoscopy, or a CEA level of at least 7 μg/l above baseline. Time-dependent receiver operating characteristic (ROC) curve analysis was used to compare the diagnostic accuracy of CEA trends with single measurements. CEA trends were estimated using linear regression. 

Results: The area under the ROC curve (AUC) for CEA trend was at least 0·820 across all 5 years of follow-up. In comparison, the AUCs for single measurements ranged from 0·623 to 0·749. Improvement was most marked at the end of the first year of follow-up, with the AUC increasing from 0·623 (95 per cent c.i. 0·509 to 0·736) to 0·880 (0·814 to 0·947). However, no individual trend threshold achieved a sensitivity above 70 per cent (30 per cent missed recurrences). 

Conclusion: Interpreting trends in CEA measurements instead of single CEA test results improves diagnostic accuracy for recurrence, but not sufficiently to warrant it being used as a single surveillance strategy to trigger further investigation. In the absence of a more accurate biomarker, monitoring trends in CEA should be combined with clinical, endoscopic and imaging surveillance for improved accuracy.

0007-1323
658-662
Shinkins, B.
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Primrose, J.N.
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Pugh, S.A.
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Nicholson, B.D.
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Perera, R.
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James, T.
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Mant, D.
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Shinkins, B.
c46e5075-35ee-4c32-aa98-06ccca2c3ea4
Primrose, J.N.
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Pugh, S.A.
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Nicholson, B.D.
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Perera, R.
d0b24f7a-0794-4563-92b9-3e624d725378
James, T.
d91c3672-79b5-41a1-a917-5920b607bff2
Mant, D.
10e94981-cd2c-4e56-8a11-54d9fc107117

Shinkins, B., Primrose, J.N., Pugh, S.A., Nicholson, B.D., Perera, R., James, T. and Mant, D. (2018) Serum carcinoembryonic antigen trends for diagnosing colorectal cancer recurrence in the FACS randomized clinical trial. British Journal of Surgery, 105 (6), 658-662. (doi:10.1002/bjs.10819).

Record type: Article

Abstract

Background: Most guidelines recommend that patients who have undergone curative resection for primary colorectal cancer are followed up for 5 years with regular blood carcinoembryonic antigen (CEA) tests to trigger further investigation for recurrence. However, CEA may miss recurrences, or patients may have false alarms and undergo unnecessary investigation. 

Methods: The diagnostic accuracy of trends in CEA measurements for recurrent colorectal cancer, taken as part of the FACS (Follow-up After Colorectal Surgery) trial (2003-2014), were analysed. Investigation to detect recurrence was triggered by clinical symptoms, scheduled CT or colonoscopy, or a CEA level of at least 7 μg/l above baseline. Time-dependent receiver operating characteristic (ROC) curve analysis was used to compare the diagnostic accuracy of CEA trends with single measurements. CEA trends were estimated using linear regression. 

Results: The area under the ROC curve (AUC) for CEA trend was at least 0·820 across all 5 years of follow-up. In comparison, the AUCs for single measurements ranged from 0·623 to 0·749. Improvement was most marked at the end of the first year of follow-up, with the AUC increasing from 0·623 (95 per cent c.i. 0·509 to 0·736) to 0·880 (0·814 to 0·947). However, no individual trend threshold achieved a sensitivity above 70 per cent (30 per cent missed recurrences). 

Conclusion: Interpreting trends in CEA measurements instead of single CEA test results improves diagnostic accuracy for recurrence, but not sufficiently to warrant it being used as a single surveillance strategy to trigger further investigation. In the absence of a more accurate biomarker, monitoring trends in CEA should be combined with clinical, endoscopic and imaging surveillance for improved accuracy.

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Accepted/In Press date: 13 December 2017
e-pub ahead of print date: 26 March 2018
Published date: 13 April 2018
Additional Information: Special Issue: Advanced colorectal cancer issue

Identifiers

Local EPrints ID: 420057
URI: https://eprints.soton.ac.uk/id/eprint/420057
ISSN: 0007-1323
PURE UUID: 1fe07818-2b84-4306-af30-2a35f9321bba
ORCID for J.N. Primrose: ORCID iD orcid.org/0000-0002-2069-7605

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Date deposited: 25 Apr 2018 16:31
Last modified: 27 Mar 2019 05:01

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Contributors

Author: B. Shinkins
Author: J.N. Primrose ORCID iD
Author: S.A. Pugh
Author: B.D. Nicholson
Author: R. Perera
Author: T. James
Author: D. Mant

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