NEJM: Colonoscopy screening may be overestimated in reducing the risk of colorectal cancer (NordICC study)

Colorectal cancer is the third most common type of cancer worldwide and the second leading cause of
cancer death.
Based on this, in the field of early cancer screening, colorectal cancer has always been one of the key targets of
the population.
The most widely used methods of colorectal cancer screening today include fecal occult blood testing and endoscopic screening (sigmoidoscopy or colonoscopy).

It should be noted that the vast majority of colorectal cancers develop from benign polyps, which means that they can be detected and removed
by endoscopy.
In current research and clinical practice, colonoscopy is the universally applied gold standard
for colorectal cancer screening.
Most current guidelines for colorectal cancer screening/expert consensus recommend colonoscopy screening
every 10 years.
As recommended by the 2022 Asia-Pacific Consensus: colorectal cancer screening and post-polypectomy surveillance

However, on October 9, 2022, the results of a large, population-based randomized trial published in the New England Journal of Medicine (NEJM) suggest that the role of colonoscopy screening in reducing the risk of colorectal cancer may be overestimated!

The NordICC trial is a large, multicenter, randomized clinical trial to evaluate the effect
of population-based colonoscopy screening on the risk of colorectal cancer and the risk of colorectal cancer-related death after 10 years.
Participants (aged 55 to 64 years) from four different countries – Poland, Norway, Sweden and the Netherlands – were randomised 1:2 to receive one-time colonoscopy screening (screening group) or no screening (usual group).

Screening was conducted between
June 8, 2009 and June 23, 2014.
All lesions identified on colonoscopy should be removed where feasible; All tumor lesions require biopsy
.
The main endpoints of the study were the risk of colorectal cancer and the risk of colorectal cancer-related death after a median follow-up of 10~15 years; The secondary endpoint was all-cause mortality
.

The follow-up data of 84,585 participants (28,220 in the screening group and 56,365 in the routine group, respectively) were reported, of which 50.
1% were male; The median age of participants at randomisation was 59 years
.
As of the current analysis, the median follow-up of participants in both groups was 10.
0 years
.

Within 10 years, the incidence of colorectal cancer in the screening group was 0.
98% (259 people) and 1.
20% (622 people) in the control group, the risk in the screening group decreased by 18%, and every 455 people screened for colonoscopy screening could prevent the occurrence
of 1 case of colorectal cancer.

Colorectal cancer incidence in the screening group (red) and control group (blue).

A total of 455 patients (95% CI: 270-1429)
required colonoscopy screening for the prevention of colorectal cancer within 10 years.
Among participants diagnosed with colorectal cancer, 0.
38% and 0.
44% were diagnosed with early colorectal cancer (stage A or B) in the screening group and control group, and 0.
40% and 0.
50%
in advanced colorectal cancer (stage C or D), respectively.

After 10 years of follow-up, the risk of colorectal cancer-related death was 0.
28% (72 deaths) in the screening group and 0.
31% (157 deaths) in the routine group (RR = 0.
90; 95% CI: 0.
64 to 1.
16), a 10% reduction in the risk, but not statistically significant
.
The paper noted that both groups had lower colorectal cancer-related mortality, which was associated with
improvements in colorectal cancer treatment options over the past 10 years.
In addition, there was no significant reduction
in mortality in participants in the screening group compared to participants who were not screened.

All-cause mortality was 11.
03% (3036 people) and 11.
04% (6079 people), respectively, and there was no significant difference in the risk of death (RR = 0.
99; 95% CI: 0.
96 to 1.
04).

Colorectal cancer-related mortality in the screening group (red) and control group (blue).

In the corrected analysis, if all participants assigned to the screening group actually received colonoscopy screening, the incidence of colorectal cancer would decrease from 1.
22% to 0.
84% (RR = 0.
69; 95% CI: 0.
55 to 0.
83) over 10 years, i.
e.
an estimated risk reduction of 31%.

Colorectal cancer-related mortality will be reduced from 0.
30% to 0.
15% (RR = 0.
50; 95% CI: 0.
27 to 0.
77), with an estimated risk reduction of 50%, and in sensitivity analyses, the risk reduction is 28%, but with low
accuracy.

Colonoscopy has long been considered an important means of preventing colorectal cancer, and most past observational studies have confirmed the benefits
of colonoscopy screening.
The authors emphasize that the current study is "the world's first randomized study using colonoscopy screening to prevent colorectal cancer," but unfortunately, based on the results of the current analysis, the preventive effect of colonoscopy screening in the risk of colorectal cancer may not be significantly better than that of fecal occult blood tests
.
The results suggest that colonoscopy may not be an effective weapon
to prevent colorectal cancer.

In the same review article, the review author gives several possible explanations
.
In the United States, colonoscopy has been the mainstay of
colorectal cancer screening.
However, the best evidence to support its use was limited to data from
cohort studies.
Unlike randomized controlled studies that support cecal occult blood testing and sigmoidoscopy, cohort studies may overestimate the effectiveness of colonoscopy in the real world because cohort studies cannot adjust for important factors such as incomplete adherence to testing and a preference for healthier people to seek preventive care
.

Original source:

Effect of Colonoscopy Screening on Risks of Colorectal Cancer and Related Death.
NEJM, DOI: 10.
1056/NEJMoa2208375