Effectiveness of Colonoscopy for Colorectal Cancer Screening in Reducing Cancer-Related Mortality: Interpreting the Results From Two Ongoing Randomized Trials
Bretthauer M, Loberg M, Wieszczy M, et al; NordICC Study Group. Effect of colonoscopy screening on risks of colorectal cancer and related death. N Engl J Med. 2022;387(17):1547-1556. doi:10.1056/NEJMoa2208375
Forsberg A, Westerberg M, Metcalfe C, et al; SCREESCO investigators. Once-only colonoscopy or two rounds of faecal immunochemical testing 2 years apart for colorectal cancer screening (SCREESCO): preliminary report of a randomised controlled trial. Lancet Gastroenterol Hepatol. 2022;7(6):513-521. doi:10.1016/S2468-1253(21)00473-8
Commentary
The first colonoscopy screening recommendations were established in the mid 1990s in the United States, and over the subsequent 2 decades colonoscopy has been the recommended method and main modality for colorectal cancer screening in this country. The advantage of colonoscopy over other screening modalities (sigmoidoscopy and fecal-based testing) is that it can examine the entire large bowel and allow for removal of potential precancerous lesions. However, data to support colonoscopy as a screening modality for colorectal cancer are largely based on cohort studies.1,2 These studies have reported a significant reduction in the incidence of colon cancer. Additionally, colorectal cancer mortality was notably lower in the screened populations. For example, one study among health professionals found a nearly 70% reduction in colorectal cancer mortality in those who underwent at least 1 screening colonoscopy.3
There has been a lack of randomized clinical data to validate the efficacy of colonoscopy screening for reducing colorectal cancer–related deaths. The current study by Bretthauer et al addresses an important need and enhances our understanding of the efficacy of colorectal cancer screening with colonoscopy. In this randomized trial involving more than 84,000 participants from Poland, Norway, Sweden, and the Netherlands, there was a noted 18% decrease in the risk of colorectal cancer over a 10-year period in the intention-to-screen population. The reduction in the risk of death from colorectal cancer was not statistically significant (risk ratio, 0.90; 95% CI, 0.64-1.16). These results are surprising and certainly raise the question as to whether previous studies overestimated the effectiveness of colonoscopy in reducing the risk of colorectal cancer–related deaths. There are several limitations to the Bretthauer et al study, however.
Perhaps the most important limitation is the fact that only 42% of participants in the invited-to-screen cohort underwent screening colonoscopy. Therefore, this raises the question of whether the efficacy noted is simply due to a lack of participation in the screening protocol. In the adjusted per-protocol analysis, colonoscopy was estimated to reduce the risk of colorectal cancer by 31% and the risk of colorectal cancer–related death by around 50%. These findings are more in line with prior published studies regarding the efficacy of colorectal cancer screening. The authors plan to repeat this analysis at 15 years, and it is possible that the risk of colorectal cancer and colorectal cancer–related death can be reduced on subsequent follow-up.
