Intensive Follow-up Increases Surgical Treatment of Recurrence With Curative Intent in Colorectal Cancer
In a study (FACS trial) reported in JAMA, Primrose et al compared outcomes with intensive follow-up with carcinoembryonic antigen measurement (CEA), computed tomography (CT), both, or minimum follow-up after curative surgery for primary colorectal cancer. Intensive strategies resulted in a significantly greater proportion of patients undergoing surgical treatment of recurrence with curative intent, but there was no apparent benefit of these strategies over minimum follow-up in overall survival or colorectal cancer–specific survival.
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).
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 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.
The four groups were generally balanced for age (median, 69–70 years), sex (61% male in all), concurrent treatment for other illness (27%–31%), chemotherapy pretreatment (40%–41%), radiotherapy pretreatment (11%–13%), site of cancer (right colon in 31%–35%, left colon in 33%–40%, rectum in 28%–34%), Dukes stage (A in 19%–24%, B in 45%–51%, C in 28%–31.5%), and smoking status (39%–43% never-smokers, 50%–55% ex-smokers).
After a mean follow-up of 4.4 years, cancer recurrence was detected in 16.6% of patents, with 3.4% having locoregional recurrence only and 8.4% having metastatic disease limited to lung or liver. Recurrence tended to be detected earlier in the intensive follow-up groups, but the differences were not statistically significant. No recurrences treatable with curative intent were detected in the minimum follow-up group after 2 years. In total, 65.3% of recurrences were detected at scheduled follow-ups, with the remainder being detected on the basis of symptoms or incidentally during investigation of concurrent illness.
Recurrence Treatment With Curative Intent
Overall, 5.9% of patients received surgical treatment with curative intent for recurrence, including 5.1% with Dukes stage A disease, 6.1% with stage B, and 6.2% with stage C. Such treatment was significantly more common in the CEA group (6.7%, adjusted odds ratio [OR] = 3.00, P = .02), CT group (8%, OR = 3.63, P = .004), and the CEA/CT group (6.6%, OR = 3.10, P = .01) vs the minimum follow-up group (2.3%). There was no significant differences in rate of such treatment between the 602 patients with CEA measurement vs 600 without (6.6% vs 5.2%, P = .28), whereas a significant difference was observed between the 601 undergoing CT vs 601 not undergoing CT (7.3% vs 4.5%, P = .04).
There was no significant difference across the four groups with regard to proportions of patients with surgical treatment with curative intent who remained alive at the time of analysis (5.0% in CEA group, 3.7% in CT group, 5.3% in CEA/CT group, and 1.7% in minimum follow-up group; P = .09). There was a significant difference in proportion of patients undergoing treatment who remained alive between those who had CEA measurement vs those who did not (5.1% vs 2.7%, P = .03) but not between those who underwent CT and those who did not (4.5% vs 3.3%, P = .30).
No Survival Differences
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). There were no significant differences between CEA and non-CEA patients (17.3% vs 18.0%, P = .25) or between CT and non-CT patients (18.0% vs 17.3%, P = .76) in overall mortality or in colorectal cancer–specific mortality (9.8% vs 10.5%, P = .69; 10.3% vs 10.0%, P = .85).
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.”
John N. Primrose, MD, FRCS, of University of Southampton, England, is the corresponding author for the JAMA article.
The study was funded by the UK National Institute for Health Research Health Technology Assessment program. Study author Peter Rose, MD, FRCGP, reported board membership with GP Update Ltd.
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