Resumen de Effect of 3 to 5 Years of Scheduled CEA and CT Follow-up to Detect Recurrence of Colorectal Cancer
John N. Primrose, Rafael Perera, Alastair Gray, Peter Rose, Alice M. Fuller, Andrea Corkhill
Importance Intensive follow-up after surgery for colorectal cancer is common practice but is based on limited evidence.
Objective To assess the effect of scheduled blood measurement of carcinoembryonic antigen (CEA) and computed tomography (CT) as follow-up to detect recurrent colorectal cancer treatable with curative intent.
Design, Setting, and Participants Randomized clinical trial in 39 National Health Service hospitals in the United Kingdom; 1202 eligible participants were recruited between January 2003 and August 2009 who had undergone curative surgery for primary colorectal cancer, including adjuvant treatment if indicated, with no evidence of residual disease on investigation.
Interventions Participants were randomly assigned to 1 of 4 groups: CEA only (n = 300), CT only (n = 299), CEA+CT (n = 302), or minimum follow-up (n = 301). Blood CEA was measured every 3 months for 2 years, then every 6 months for 3 years; CT scans of the chest, abdomen, and pelvis were performed every 6 months for 2 years, then annually for 3 years; and the minimum follow-up group received follow-up if symptoms occurred.
Main Outcomes and Measures The primary outcome was surgical treatment of recurrence with curative intent; secondary outcomes were mortality (total and colorectal cancer), time to detection of recurrence, and survival after treatment of recurrence with curative intent.
Results After a mean 4.4 (SD, 0.8) years of observation, cancer recurrence was detected in 199 participants (16.6%; 95% CI, 14.5%-18.7%) overall; 71 of 1202 participants (5.9%; 95% CI, 4.6%-7.2%) were treated for recurrence with curative intent, with little difference according to Dukes staging (stage A, 5.1% [13/254]; stage B, 6.1% [34/553]; stage C, 6.2% [22/354]). Surgical treatment of recurrence with curative intent was 2.3% (7/301) in the minimum follow-up group, 6.7% (20/300) in the CEA group, 8% (24/299) in the CT group, and 6.6% (20/302) in the CEA+CT group. Compared with minimum follow-up, the absolute difference in the percentage of patients treated with curative intent in the CEA group was 4.4% (95% CI, 1.0%-7.9%; adjusted odds ratio [OR], 3.00; 95% CI, 1.23-7.33), in the CT group was 5.7% (95% CI, 2.2%-9.5%; adjusted OR, 3.63; 95% CI, 1.51-8.69), and in the CEA+CT group was 4.3% (95% CI, 1.0%-7.9%; adjusted OR, 3.10; 95% CI, 1.10-8.71). The number of deaths was not significantly different in the combined intensive monitoring groups (CEA, CT, and CEA+CT; 18.2% [164/901]) vs the minimum follow-up group (15.9% [48/301]; difference, 2.3%; 95% CI, −2.6% to 7.1%).
Conclusions and Relevance Among patients who had undergone curative surgery for primary colorectal cancer, intensive imaging or CEA screening each provided an increased rate of surgical treatment of recurrence with curative intent compared with minimal follow-up; there was no advantage in combining CEA and CT. If there is a survival advantage to any strategy, it is likely to be small.
Trial Registration isrctn.org Identifier: 41458548 Colorectal cancer is a major cause of morbidity and mortality. It is the third most common cancer worldwide, with 1.24 million cases reported to the International Agency for Research on Cancer in 2008.1 Traditionally, patients who have had curative treatment for colorectal cancer undergo regular hospital follow-up for at least 5 years to detect recurrence. Although locoregional relapse is traditionally associated with poor prognosis, specialist centers are reporting improved cure rates for selected patients with combined-mode treatment.2 Success in treating metastatic recurrence has also been increasing. Approximately 40% of patients survive 5 years after complete resection of liver metastases3 and comparable results have been reported for lung metastases.4 The likelihood of survival is increased if metastatic disease is treated before it becomes symptomatic.5 Seven published clinical trials have compared different follow-up regimens.6- 12 Two systematic reviews suggest an overall survival benefit associated with more intensive follow-up.13,14 However, trial quality was modest, the estimated effect on disease-specific survival was not statistically significant, and the mechanism by which the substantial survival benefits reported were achieved is unclear. Two reviews13,14 concluded that the existing evidence base needed to be strengthened by high-quality trials addressing the effectiveness of the individual components of follow-up.
The 2 individual components of follow-up recognized to be widely available and affordable and to have the potential to detect isolated metastatic recurrence at an early and surgically treatable stage are computed tomography (CT) imaging of the chest, abdomen, and pelvis and regular blood carcinoembryonic antigen (CEA) measurement. The FACS (Follow-up After Colorectal Surgery) trial was commissioned by the UK National Institute for Health Research Health Technology Assessment program to assess the effect of these 2 modes with the intention of providing a sound evidence base to inform clinical practice. The original intention was to conduct a trial of sufficient size to assess survival advantage but when this proved infeasible, detection of recurrence that was treatable surgically with curative intent was chosen as the main outcome measure. Pretrial modeling suggested that unless follow-up increased the number of such recurrences detected, an important survival advantage of follow-up would not be achieved.
