In the FACS trial, reported in JAMA, John N. Primrose, MD, FRCS, of University of Southampton, England, and colleagues compared outcomes with intensive follow-up with carcinoembryonic antigen (CEA) measurement, computed tomography (CT), both, or minimum follow-up after curative surgery for primary colorectal cancer.¹ Intensive strategies resulted in a significantly greater proportion of patients undergoing surgical treatment of recurrence with curative intent. 

Study Details

In the trial, 1,202 patients who had undergone curative surgery for primary colorectal cancer, including adjuvant treatment if indicated, between January 2003 and August 2009 at 39 UK hospitals were randomly assigned to CEA only (n = 300), CT only (n = 299), CEA/CT (n = 302), or minimum follow-up (n = 301) to detect recurrent cancer treatable with curative intent (primary endpoint). Patients had to have no residual disease, microscopically clear margins, and Dukes stage A to C (TNM stage 1–3) disease; patients were disease-free based on colon imaging with no evidence of metastatic disease, as confirmed by CT or magnetic resonance imaging liver scan and chest CT scan, and had postoperative blood CEA level ≤ 10 μg/L after surgery or adjuvant therapy.

CEA was measured every 3 months for 2 years and then every 6 months for 3 years. CT scans of the chest, abdomen, and pelvis were performed every 6 months for 2 years and then annually for 3 years. The minimum follow-up group had no scheduled follow-up except a single CT scan of the chest, abdomen, and pelvis at 12 to 18 months if requested at study entry by hospital clinicians; otherwise, patients received follow-up if symptoms occurred.

Patients had a mean age of 69 years, 61% were male, 29% had significant comorbidity, 41% had received adjuvant chemotherapy and 12% had received preoperative radiotherapy. Treatment groups were balanced for baseline characteristics. Dukes stage was A in 19% to 24%, B in 45% to 51%, and C in 28% to 31.5%. 

Increased Surgical Treatment With Curative Intent

After mean follow-up of 4.4 years, cancer recurrence was detected in 16.6% of patents. Overall, 5.9% of patients received surgical treatment with curative intent for recurrence, with there being little difference according to Dukes staging—ie, 5.1% of patients with  Dukes stage A, 6.1% with stage B, and 6.2% with stage C. Surgical treatment of recurrence with curative intent occurred in 2.3% of patients in the minimum follow-up group, 6.7% in the CEA group, 8.0% in the CT group, and 6.6% in the CEA/CT group (P = .02 for trend).

Compared with minimum follow-up, the absolute difference in percentage treated with curative intent was 4.4% (adjusted odds ratio [OR]= 3.00, P = .02) in the CEA group, 5.7% (adjusted OR = 3.63, P = .004) in the CT group, and 4.3% (adjusted OR = 3.10, P = .01) in the CEA/CT group. The odds ratio for the CEA/CT group was similar to that with CT or CEA alone, suggesting that no additive effect is achieved by using both together.

The intensive interventions tended to detect recurrence earlier, although differences in earlier detection were not statistically significant. No patients in the minimum follow-up group had curative resection after 2 years, whereas curative resections were performed in patients in all of the intensive groups beyond 2 years (P = .03).

Survival

The trial was not powered to detect difference in survival. There was no significant difference across the four groups with regard to overall mortality (18.7% in CEA group, 20.1% in CT group, 15.9% in CEA/CT group, and 15.9% in minimum follow-up group; P = .45) or colorectal cancer–specific mortality (10.7%, 11.7%, 8.9%, and 9.3%; P = .66).

The investigators noted, “Although the observed 2% aggregate survival advantage of the minimum follow-up group vs the more intensive follow-up groups is unlikely to be due to bias (central death registration in the United Kingdom means there was no loss to follow-up), it could be due to chance. An observed absolute 6% increase in surgery with curative intent predicts a 2% to3% survival advantage with intensive follow-up. The confidence intervals around both the total mortality and colorectal cancer–specific mortality rates indicate that our results are still consistent with this outcome.”

The investigators concluded, “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.” ■

Disclosure: The study was funded by the UK National Institute for Health Research Health Technology Assessment program. For full disclosures of the study authors, visit jama.jamanetwork.com.

Reference

1. Primrose JN, Perera R, Gray A, et al: Effect of 3 to 5 years of scheduled CEA and CT follow-up to detect recurrence of colorectal cancer: The FACS randomized clinical trial. JAMA 311:263-270, 2014.