How Much Does Colonoscopy Reduce Colon Cancer Mortality?

What is the effectiveness of colonoscopy in reducing colorectal cancer (CRC) mortality? Because we do not have direct evidence from a randomized, controlled trial (RCT), we must rely on indirect evidence. In this issue, Baxter and colleagues' case–control study (1) raises interesting and troubling questions about how much screening colonoscopy reduces CRC mortality. The authors used a province-wide administrative database in Ontario, Canada, to identify case patients who received a diagnosis of CRC from 1996 to 2001 and died by 2003. Five randomly selected controls who did not die of CRC were matched to each case patient. Exposure to previous colonoscopy was assessed from billing claims for case patients and controls. Among 10 292 case patients, 7.0% had previous colonoscopy, whereas among 51 460 controls, 9.8% had a previous colonoscopy. The odds ratio for the association between complete colonoscopy and CRC mortality reduction was 0.33 for left-sided lesions, which suggests a large mortality reduction. However, the result was dramatically different for right-sided lesions: An odds ratio of 0.99 indicated a roughly 1% mortality reduction, which is essentially none at all.

These results raise 3 important questions. First, are the results valid enough to warrant serious consideration if the study uses a case–control design—an inherently weaker design than a RCT? Second, presuming they are valid, which reasons—especially those that might be remediable—might explain the low effectiveness for cancer in the right colon? Finally, how does this study help us fairly consider the magnitude of colonoscopy effectiveness in reducing CRC mortality?

Case–control studies are susceptible to numerous biases (2), but several features of this study's design and results suggest that the study must be taken seriously. One possible limitation is that it was impossible to tell whether colonoscopy “exposure” was for screening asymptomatic persons or for diagnosing cancer. If cancer symptoms led to …