title: The diagnostic accuracy of a single CEA blood test in detecting colorectal cancer recurrence: Results from the FACS trial.
abstract: OBJECTIVE
  To evaluate the diagnostic accuracy of a single CEA (carcinoembryonic antigen) blood test in detecting colorectal cancer recurrence.
  
  
  BACKGROUND
  Patients who have undergone curative resection for primary colorectal cancer are typically followed up with scheduled CEA testing for 5 years. Decisions to investigate further (usually by CT imaging) are based on single test results, reflecting international guidelines.
  
  
  METHODS
  A secondary analysis was undertaken of data from the FACS trial (two arms included CEA testing). The composite reference standard applied included CT-CAP imaging, clinical assessment and colonoscopy. Accuracy in detecting recurrence was evaluated in terms of sensitivity, specificity, likelihood ratios, predictive values, time-dependent area under the ROC curves, and operational performance when used prospectively in clinical practice are reported.
  
  
  RESULTS
  Of 582 patients, 104 (17.9%) developed recurrence during the 5 year follow-up period. Applying the recommended threshold of 5μg/L achieves at best 50.0% sensitivity (95% CI: 40.1-59.9%); in prospective use in clinical practice it would lead to 56 missed recurrences (53.8%; 95% CI: 44.2-64.4%) and 89 false alarms (56.7% of 157 patients referred for investigation). Applying a lower threshold of 2.5μg/L would reduce the number of missed recurrences to 36.5% (95% CI: 26.5-46.5%) but would increase the false alarms to 84.2% (924/1097 referred). Some patients are more prone to false alarms than others-at the 5μg/L threshold, the 89 episodes of unnecessary investigation were clustered in 29 individuals.
  
  
  CONCLUSIONS
  Our results demonstrated very low sensitivity for CEA, bringing to question whether it could ever be used as an independent triage test. It is not feasible to improve the diagnostic performance of a single test result by reducing the recommended action threshold because of the workload and false alarms generated. Current national and international guidelines merit re-evaluation and options to improve performance, such as making clinical decisions on the basis of CEA trend, should be further assessed.
authors.affiliation: Test Evaluation Group, Academic Unit of Health Economics, University of Leeds, Leeds, United Kingdom.
authors.forename: Bethany
authors.identifier: http://orcid.org/0000-0001-5350-1018
authors.initials: B
authors.lastname: Shinkins
authors.affiliation: Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, United Kingdom.
authors.forename: Brian D
authors.initials: BD
authors.lastname: Nicholson
authors.affiliation: Academic Unit of Cancer Sciences, University of Southampton, Southampton, United Kingdom.
authors.forename: John
authors.initials: J
authors.lastname: Primrose
authors.affiliation: Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, United Kingdom.
authors.forename: Rafael
authors.initials: R
authors.lastname: Perera
authors.affiliation: Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom.
authors.forename: Timothy
authors.initials: T
authors.lastname: James
authors.affiliation: Academic Unit of Cancer Sciences, University of Southampton, Southampton, United Kingdom.
authors.forename: Sian
authors.initials: S
authors.lastname: Pugh
authors.affiliation: Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, United Kingdom.
authors.forename: David
authors.initials: D
authors.lastname: Mant
mesh_terms: D019540:Area Under Curve; D002272:Carcinoembryonic Antigen / Q000097:blood*; D003113:Colonoscopy; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000473:pathology / Q000601:surgery; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D009364:Neoplasm Recurrence, Local; D011237:Predictive Value of Tests; D012372:ROC Curve; D012680:Sensitivity and Specificity; D014057:Tomography, X-Ray Computed
chemical_list: D002272:Carcinoembryonic Antigen