First Randomized Controlled Trial Comparing Colonoscopy With No Screening Finds Less Benefit Than Expected for Colonoscopy

COMMENT

This study shows a reduction in CRC incidence with colonoscopy compared with usual care, but the reduction in rate is low in the intent-to-screen analysis and numerically lower than in some sigmoidoscopy trials. In the U.S., where colonoscopy is widely accepted, the per-protocol analysis is of greatest importance. In the U.S., we should move the discussions with media and patients away from the intent-to-screen analysis to the per-protocol analysis. There are some issues with the study:

• The minimal shift in cancer stage in the invited group suggests the patients could reflect some bias toward high-risk or symptomatic patients undergoing colonoscopy.
• The overall ADR was 31%. An accompanying editorial noted that the investigators previously reported that 29% of endoscopists were below the current U.S.-recommended minimum ADR threshold of 25%. Recent registry data indicate ADRs in the U.S. now average 40%.
• There are no data on adenomas per colonoscopy, which would provide additional information on how well colons were cleared.
• The extent to which patients with adenomas underwent appropriate surveillance is not known. 
• The higher incidence reduction in the per-protocol analysis in Norway (45%) versus Poland (15%) is unexplained.
• In the intent-to-screen arm, the incidence reduction was higher than the mortality reduction, which is unexpected.

Given the issues noted here and the short follow-up for an RCT of this type, the study’s estimate of the reduction in cancer incidence associated with screening colonoscopy is almost certainly low. The study supports that sending out invitations for colonoscopy is inadequate and that colonoscopy must be done well. Hopefully, the limitations will be widely understood and not set colorectal cancer screening back. For now, this study should not affect our approach or commitment to colorectal cancer screening.