The CEA Second-Look Trial: a randomised controlled trial of carcinoembryonic antigen prompted reoperation for recurrent colorectal cancer

Abstract

ObjectiveIn patients who have undergone a potentially curative resection of colorectal cancer, does a ‘second-look’ operation to resect recurrence, prompted by monthly monitoring of carcinoembryonic antigen, confer a survival benefit?DesignA randomised controlled trial recruiting patients from 1982 to 1993 was recovered under the Restoring Invisible and Abandoned Trials (RIAT) initiative.Setting58 hospitals in the UK.ParticipantsFrom 1982 to 1993, 1447 patients were enrolled. Of these 216 met the criteria for carcinoembryonic antigen (CEA) elevation and were randomised to ‘Aggressive’ or ‘Conventional’ arms.Interventions‘Second-look’ surgery with intention to remove any recurrence discovered.Primary outcome measureSurvival.ResultsBy February 1993, 91/108 patients had died in the ‘Aggressive arm’ and 88/108 in the ‘Conventional’ arm (relative risk=1.16, 95% CI 0.87 to 1.37). By 2011 a further 25 randomised patients had died. Kaplan-Meier analysis showed no difference in long-term survival.ConclusionsThe trial was closed in 1993 following a recommendation from the Data Monitoring Committee that it was highly unlikely that any survival advantage would be demonstrated for CEA prompted second-look surgery. This conclusion was confirmed by repeat analysis of survival times after 20 years.Trial registration numberISRCTN76694943.

Head-to-Head Comparison and Evaluation of 92 Plasma Protein Biomarkers for Early Detection of Colorectal Cancer in a True Screening Setting

“…However, due to its limited sensitivity especially for early stage cancer, and its limited organ specificity, CEA is not regarded as suited as an individual diagnostic marker despite its undisputed value for monitoring tumor recurrence (35,36) and metastasis (37,38). In our analyses, CEA was found to have higher plasma levels in colorectal cancer patients at advanced stages compared with early ones, which is consistent with previous evidence (39).…”

Intensified follow-up in colorectal cancer patients using frequent Carcino-Embryonic Antigen (CEA) measurements and CEA-triggered imaging: Results of the randomized “CEAwatch” trial

“…An analysis on older data using CEA showed a lack of survival improvement for second-look operations based on CEA rise. 33 The FACS trial, a randomized trial comparing minimal and intensive follow-up, recently confirmed that regular CEA measurements, CT scanning and CEA with CT scanning result in significantly higher rates of curable recurrences compared to minimum follow-up (resp 7.6%, 9.5%, 7.3% and 1.5). 34 However there was no survival improvement between the different follow-up protocols in this study.…”

A randomised controlled trial to assess the cost-effectiveness of intensive versus no scheduled follow-up in patients who have undergone resection for colorectal cancer with curative intent

“…The MRC-funded UK CEA trial 12 recruited a large number of patients (n = 1447). It was conducted between 1982 and 1993, when patients with recurrent cancer were not managed as they are now (i.e.…”

“…11 At the time that the Follow-up After Colorectal Surgery (FACS) trial was designed, this trial had not demonstrated any benefit from the intervention, and a subsequent publication confirmed this. 12 However, the trial suffers from the criticism that patients who developed recurrence were not commonly offered treatments that could impact on survival, such as liver/lung resection. Of the non-randomised trials, a meta-analysis suggested benefit if the follow-up strategy included CEA testing.…”