Colonoscopy is one of the options available for colorectal cancer screening. It is mainly used in the United States for this indication and commonly in Germany. But unlike other modalities such as fecal occult blood tests (FIT for Fecal Immunochemical Test) and sigmoidoscopy, it had never been evaluated in a randomized controlled trial.
A trial called the Nordic-European Initiative on Colorectal Cancer (NordICC) attempted to fill this gap. The results of this randomized controlled trial* were published in “The New England Journal of Medicine”. “This is an article that has been awaited for 10 years, because no test of this type had ever been carried out”, comments Professor Robert Benamouzig, head of the gastroenterology department at the Avicenne hospital in Bobigny (Seine-Saint-Denis) and member of the French National Society of Gastroenterology (SNFGE).
Data from cohort studies had estimated that this examination was associated with a 40 to 69% reduction in the incidence of colorectal cancer and a 29 to 88% reduction in the specific risk of death. But the real effectiveness of colonoscopy could be overestimated, because these studies struggle to take into account reluctance to participate in colonoscopy for screening.
Conducted in Poland, Norway, Sweden and the Netherlands between 2009 and 2014, the NordICC trial involved 84,585 presumably healthy participants aged 55 to 64. Among them, 28,220 received an invitation to perform a screening colonoscopy. The other 56,365 received usual care, which could include a colonoscopy if needed. “Two criteria were evaluated: the rate of participation in colonoscopy screening after an invitation and the difference in cancer risk at 10 years depending on the strategy adopted”underlines Professor Benamouzig.
It first shows that, in these countries where screening colonoscopy was uncommon, only 42% of participants invited to screening actually performed the examination, with variations depending on the country ranging from 33% in Poland to 60 .7% in Norway.
An 18% reduction in the risk of colorectal cancer at 10 years
In intent-to-screen analyses, the 10-year risk of colorectal cancer was 0.98% in the invited group and 1.20% in the usual care group, an 18% risk reduction (relative risk at 0.82). “This 18% reduction in risk provides evidence that the invitation to colonoscopy probably reduces mortality. Above all, this study quantifies the effect, which turns out to be close to that obtained with FIT, which reduces the risk of colorectal cancer by 15%, while the rates of participation in colonoscopy are lower than for FIT”says Professor Benamouzig.
Furthermore, the study puts the risk of death from colorectal cancer at 0.28% in the invited group and 0.31% in the usual care group (relative risk at 0.90), while the risk of death, all causes, was similar in the two groups: 11.03% in the guest group and 11.04% in the usual care group. “The necessary number of patients to be invited for screening to prevent one case of colorectal cancer was 455”say the authors.
Despite their interest, these results had little echo, particularly in France, is surprised the head of the Avicenne hospital department, “maybe the amount of benefits is less than expected”. Yet, he continues, “this is the first time that the amount of protective effect associated with the proposal to perform a colonoscopy has been documented”.
Cost-effective screening still to be defined
In analyzes adjusted to estimate the effect of screening if all randomly assigned participants actually participated, the risk of colorectal cancer fell from 1.22% to 0.84%, and the risk of colorectal cancer-related death from 0.30% to 0.15%. Thus, 100% participation would lead to a 31% reduction in the risk of colorectal cancer and a 50% reduction in associated deaths. This benefit is “probably underrated”judge the authors, because, “As in most other large-scale colorectal cancer screening trials, we could not adjust for all significant confounders in all countries”they explain.
The challenge therefore remains participation in screening. “In Latin countries, the colonoscopy participation rate peaks at around 25%. In France, we already sensed, according to the non-randomized data in the literature, the expected effect described in the study, which was roughly similar to that of FIT. However, it is much more cost-effective to do a FIT followed by a colonoscopy in 4% of cases than to offer it to all French people over 45 or 50 years old.believes Professor Benamouzig.
A randomized trial currently being conducted in Spain to compare colonoscopy to FIT should shed further light on the benefits of each of the screening methods. The first results, presented informally during the French-speaking days of hepato-gastroenterology and digestive oncology in Paris from March 16 to 19, will be published in the coming year.
Another issue of screening by colonoscopy relates to the quality of the examination, which depends on the equipment but also on the operator. “The discipline’s current challenge is to have the best possible endoscopists, through quality initial training and continuous ongoing training. It is a daily work that has only just begun”insists Professor Benamouzig.
*M. Bretthauer et al. NEJM, 2022. DOI: 10.1056/NEJMoa2208375