In a randomized clinical trial (RCT) of 2,509 patients with stage II or III colorectal cancer, follow-up computed tomography (CT) and serum carcinoembryonic antigen (CEA) testing five times versus two times did not yield a significant difference in five-year overall or cancer-specific mortality rate. Overall, 1,253 patients were randomly assigned to be tested 6, 12, 18, 24, and 36 months after surgery, and 1,256 were randomly assigned to be tested 12 and 36 months after surgery. Those tested five times had overall and cancer-specific mortality rates of 13.0% and 10.6% at five years, while those tested twice had mortality rates of 14.1% and 11.4%, respectively.
The study was published in the May 22/29 JAMA. The following commentary by William T. Clarke, MD, and Joseph D. Feuerstein, MD, appeared in the ACP Journal Club section of the Oct. 16 Annals of Internal Medicine.
Testing with CT, CEA, and colonoscopy is recommended by multiple guidelines for early detection of colorectal cancer recurrence after curative surgery. However, studies are inconclusive about the comparative effectiveness of differing surveillance schedules, and guidelines differ in their recommendations for surveillance. In the COLOFOL RCT, groups randomized to CT of the chest and torso and serum CEA 2 vs 5 times done over 36 months after surgery did not differ for 5-year overall mortality or cancer-specific mortality.
This pragmatic RCT had high adherence to protocol, was methodologically sound, and reflects real-life clinical care. The findings help to clarify the ideal process for surveillance of clinical recurrence. A less-intensive testing strategy has many advantages. Less intensive surveillance would provide cost savings with 3 fewer CT scans and CEA tests. Fewer CT scans would expose patients to less radiation and the theoretical associated cancer risk. Additionally, reduced frequency of testing may result in fewer incidental findings and false-positive results—and the associated psychological stress.
The data from COLOFOL support the results of the 2013 FACS trial and a 2016 meta-analysis, neither of which found a survival benefit with increased testing. Taken together, these findings suggest that although a more-intensive screening regimen may lead to earlier detection of recurrent cancer, earlier detection does not confer a survival advantage. The well-designed COLOFOL study clearly indicates that more prudent testing is just as effective and may provide several secondary benefits.