For colorectal cancer patients who have undergone curative surgery, follow-up with either CT or a blood test increases the rate at which they'll receive surgery again, but it doesn't appear to have a big effect on patient survival, according to a study in the January 15 Journal of the American Medical Association.
Researchers in the U.K. followed 1,202 patients postsurgery who were randomly assigned to receive received CT, blood measurement of carcinoembryonic antigen (CEA), both tests, or minimum follow-up.
Among 199 patients who experienced a cancer recurrence, surgical treatment of recurrence with curative intent was higher in groups that underwent intensive follow-up with either CT or CEA compared to minimum follow-up, wrote Dr. John Primrose and colleagues. Combining the two follow-up tests conferred no additional benefit (JAMA, Vol. 311:3, pp. 263-270).
"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," the authors from the University of Southampton and the University of Oxford wrote. "If there is a survival advantage to any strategy, it is likely to be small."
Improving survival rates
Colorectal cancer patients who have received curative resection typically undergo five years of follow-up, and survival after locoregional relapse and metastatic disease have both been improving beyond the traditional five-year window, the authors wrote.
The evidence suggests that more intensive follow-up is beneficial, but in several previous trials the survival improvement was modest and the follow-up methods were not always clearly spelled out, they wrote.
Inasmuch as CT of the chest, abdomen, and pelvis and regular CEA testing are the two demonstrated methods of detecting recurrence in time for curative resection, the goal of the Follow-up After Colorectal Surgery (FACS) trial was to determine the superiority of either method -- or both used together.
The study team recruited 1,202 eligible colorectal cancer patients from 39 U.K. hospitals between 2003 and 2009 who had undergone curative surgery for primary colorectal cancer. Adjuvant treatment was included, and no patients in the study had evidence of recurrent disease.
The patients were assigned randomly to one of four groups: CEA only (300 patients), CT only (299), CEA + CT (302), or minimum follow-up (301).
For the CEA groups, blood was measured every three months for the first two years, then every six months for three years thereafter. For the CT groups, scans of the chest, abdomen, and pelvis were performed every six months for two years, then every year for three years. The minimum follow-up group was examined if any symptoms occurred, the authors noted.
The primary outcome was surgical treatment of recurrence with curative intent. Mortality -- total and from colorectal cancer -- was a secondary outcome.
After a mean 4.4 years of observation, the researchers noted cancer recurrence in 199 participants (16.6%) overall. Seventy-one (5.9%) of the 1,202 participants were treated for recurrence with curative intent, with little difference according to staging, the authors wrote.
Treatment with curative intent occurred in 2.3% of the minimum follow-up patients, 6.7% of the CEA patients, 8% of the CT patients, and 6.6% of the CEA + CT patients.
"Surgical treatment of recurrence with curative intent was higher in each of the three more intensive follow-up groups compared with the minimum follow-up group," Primrose and colleagues wrote.
The number of deaths was higher but not significantly different in the more intensive follow-up groups, at 18.2%, compared with 15.9% for the minimum follow-up group.
"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," the authors wrote. "If there is a survival advantage to any strategy, it is likely to be small."
Follow-up options
Meta-analyses have suggested that CT and CEA are the only viable follow-up strategies for detecting colorectal cancer recurrence in time for curative surgery. Clinical and ultrasound follow-up both lack sensitivity, and MRI has proved effective only for liver metastases, the authors wrote. PET/CT wasn't available at the facility when the study was undertaken.
The current study's results suggest that either CT or CEA is helpful in detecting recurrence. The difference in the proportion of participants treated with curative intent was about 5% in the intention-to-treat analysis, suggesting that about 12 to 20 patients need to be followed up to detect a cancer recurrence. In addition, more than two-thirds of the patients treated with curative intent were still alive four years after recurrence, "suggesting that five-year survival may be more than the 40% previously reported," they wrote.
The results also suggest that monitoring with a single CT scan at 12 to 18 months after surgery is as effective as regular CT scanning.
"Because CEA testing can be done in primary care, it is likely to be more cost-effective than regular CT imaging," Primrose and colleagues wrote. "However, imaging is still necessary to confirm recurrence, and in the combined CT plus CEA group, two-thirds of the recurrences were first detected by CT."
The performance of CEA depends on the frequency of testing and the algorithm used to interpret the results, they wrote. The benefits of follow-up appear to be independent of stage, but the decision on whether the absolute benefit of follow-up is at least equal to the opportunity cost will depend on the specific healthcare economy.
As for study limitations, the relatively small number of participants and the 15.9% mortality rate means the study had only 31% power to detect a 5% difference in survival, the authors noted. But the confidence intervals associated with both all-cause mortality and colorectal cancer mortality are consistent with an improvement in outcomes.
CT and CEA each "provided an improved rate of recurrence treated with curative intent compared to minimal follow-up," the authors concluded. The benefit of follow-up is likely to be small, however, and using both CEA and CT offered no additional benefit.
