Effects of screening colonoscopy in preventing colorectal cancer: re-analysis of the NordICC trial

Background. In the NordICC trial, the first randomized trial reporting on the effects of screening colonoscopy, reduction of colorectal cancer (CRC) incidence during 10 years of follow-up was estimated as 18% in intention-to-screen analysis, and 31% in adjusted per-protocol analysis. However, the „incident“ cases considered in these analyses included large proportions of CRCs that were already prevalent at recruitment and could not possibly have been prevented by the screening. We derived effect estimates for the reduction of truly incident, actually preventable cases from the published trial results. Methods. Numbers of truly incident cases, which were directly observable only among screening attenders, were estimated for all groups of participants under the following plausible assumptions: (i) equal CRC prevalence and incidence in the invited and the usual-care group in the absence of screening effects (plausible due to the randomized design and the large sample size), and (ii) equal share of prevalent CRC cases among all CRC cases in screening non-attenders and attenders in the absence of screening effects (assumption needed for intention-to-screen analyses only). We calculated screening effects with respect to reduction of truly incident cases. Results. With relative risk estimates (95% CI) of 0.72 (0.59-0.91) and 0.43 (0.26-0.78), offer and use of screening colonoscopy were estimated to reduce truly incident cases by 28% in intention-to-screen analysis and by 57% in adjusted per-protocol analysis. Conclusion. The ability of screening colonoscopy to prevent incident CRC is much stronger than originally reported from the so far only RCT on long-term effects of screening colonoscopy.