Either intensive CT imaging or frequent testing of blood levels of carcinoembryonic antigen is more likely to detect a colon cancer recurrence than is minimal follow-up, according to a report published online Jan. 14 in JAMA.
However, combining the two monitoring strategies doesn’t add to the effectiveness of either one at detecting recurrences, said Dr. John N. Primrose of the University of Southampton (England) and his associates in the FACS (Follow-Up After Colorectal Surgery) randomized clinical trial.
Several previous trials have compared different follow-up strategies for patients who have undergone potentially curative surgery – monitoring that is done in the hope that survival will be increased if metastatic disease is identified and treated before it becomes symptomatic. But these studies were of "modest" quality and failed to show any significant treatment effect on disease-specific survival, prompting calls for higher-quality trials.
Dr. John N. Primrose
The FACS, commissioned by the U.K. National Institute for Health Research, was undertaken to assess the two follow-up strategies that are available and affordable and have the greatest potential to detect isolated metastatic recurrence at an early, surgically treatable stage: serial CEA measurement and serial CT imaging of the chest, abdomen, and pelvis.
The FACS involved 1,202 patients already treated for primary colon cancer who had no residual disease and microscopically clear margins. They were scheduled to be followed for 5 years at 39 medical centers in the United Kingdom.
These participants were randomly assigned to any one of four study groups:
• CEA follow-up, with measurement of blood CEA every 3 months for 2 years, then every 6 months for the remaining 3 years, and with a single CT scan at 18 months of the chest, abdomen, and pelvis (302 patients).
• CT follow-up, with CT scans of the same regions every 6 months for 2 years, then annually for the remaining 3 years (302 patients).
• Combined CEA and CT follow-up (303 patients).
• Minimal follow-up (the control group), with only a single CT scan at 12-18 months if the hospital clinician requested one at study entry (304 patients).
Follow-up colonoscopy was provided to all the patients because it is standard treatment in such cases.
Colon cancer recurred in 199 patients.
The primary outcome measure was surgery for colon cancer recurrence after a minimum of 3 years, to help distinguish true recurrence from residual disease that was missed at the initial surgery. (Neither overall nor cancer-specific mortality could be used as a primary outcome measure because the sample size was too small and the follow-up period too short for sufficient power to estimate survival accurately.)
This rate was higher with all of the interventions, compared with minimal follow-up. Surgery for recurrence was performed in 6.7% of the CEA-only group, 8% of the CT-only group, and 6.6% of the combined CEA plus CT group, compared with only 2.3% of the control group, according to the investigators (JAMA 2014;311:263-70 [doi:10.1001/jama.2013.285718]).
These rates for the three intensive interventions were not significantly different from each other, indicating that CEA and CT follow-up yielded comparable early detection of recurrences. No additive effect was seen for combining the two strategies.
The results of a per-protocol analysis, which excluded the 308 patients who did not adhere strictly to the study protocol, were consistent with those of the main analysis.
The study findings indicate that only 12-20 patients need to be followed up using either CEA or CT to identify one potentially curable recurrence, Dr. Primrose and his associates said.
They added that they are continuing follow-up so they can more accurately assess disease-specific mortality. "If there is a survival advantage to any [follow-up] strategy, it is likely to be small," they noted.
The FACS trial was funded by the U.K. National Institute for Health Research Health Technology Assessment program. No financial conflicts of interest were reported.