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 g/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 0820 across all 5 years of follow-up. In comparison, the AUCs for single measurements ranged from 0623 to 0749. Improvement was most marked at the end of the first year of follow-up, with the AUC increasing from 0623 (95 per cent c.i. 0509 to 0736) to 0880 (0814 to 0947). 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.