After surgery for stage II or III colorectal cancer, more vs less frequent follow-up did not differ for 5-year mortality

Question After curative surgery for stage II or III colorectal cancer, does more vs less frequent follow-up with computed tomography (CT) and serum carcinoembryonic antigen (CEA) testing reduce all-cause and colorectal cancer mortality? Methods Design Randomized controlled trial (RCT) (COLOFOL trial). ClinicalTrials.gov NCT00225641. Allocation Concealed. * Blinding Unblinded. * Follow-up period Median 5 years. Setting 24 centers in Denmark, Sweden, and Uruguay. Patients 2555 patients 75 years of age (mean age 64 y, 55% men) who had curative surgery for stage II or III colorectal cancer, neoplasia-free colon and rectum confirmed by perioperative barium enema or colonoscopy 3 months after surgery, 1 liver imaging procedure and CT or radiography of the lungs before surgery, and CEA testing 1 month after surgery with a negative workup for elevated CEA levels. Exclusion criteria included colorectal cancer local resection, familial adenomatous polyposis or hereditary nonpolyposis colorectal cancer, life expectancy <2 years due to comorbid conditions, or previous cancer other than nonmelanoma skin cancer. Intervention High-frequency follow-up with thorax and abdomen CT and CEA at 6, 12, 18, 24, and 36 months after surgery (n =1275) or low-frequency follow-up using the same tests at 12 and 36 months (n =1280). Outcomes Outcomes were all-cause and colorectal cancer mortality (primary) and colorectal cancer recurrence. 2500 patients were needed to detect an absolute 6% difference in {overall mortality} with more vs less frequent follow-up (85% power, 2-sided =0.05, expected dropout rate 20%). Patient follow-up 98% included in the intention-to-treat analysis. Main results A median 5 vs 2 CTs were done in the high- vs low-frequency groups. The main results for mortality and recurrence are in the Table. Conclusion In stage II or III colorectal cancer, more vs less frequent follow-up after curative surgery did not differ for all-cause or colorectal cancer mortality at 5 years. High- vs low-frequency follow-up with carcinoembryonic antigen and computed tomography after curative surgery for stage II or III colorectal cancer Outcomes Event rates at 5 y RRR (95% CI) at a median 5 y High-frequency follow-up Low-frequency follow-up All-cause mortality 13% 14% 7.2% (13 to 24) Colorectal cancer mortality 10.6% 11.4% 6.4% (17 to 25) RRI (CI) at a median 5 y Colorectal cancer recurrence 22% 19% 12% (5 to 30) Abbreviations defined in Glossary. RRR, RRI, and CI calculated from event rates in article. Based on Kaplan-Meier estimates. Commentary Testing with CT, CEA, and colonoscopy is recommended by multiple guidelines for early detection of colorectal cancer recurrence after curative surgery (1, 2). 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 resultsand the associated psychological stress. The data from COLOFOL support the results of the 2013 FACS trial (3) and a 2016 meta-analysis (4), 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.