Change cognition! NEJM over 80,000 people study: colorectal cancer screening "gold standard", role or overestimated?

▎WuXi AppTec content team editor

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.
At present, the colorectal cancer screening guidelines/expert consensus formulated by academic groups at home and abroad recommend colonoscopy screening
every 10 years.

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!

Screenshot source: NEJM

The paper points out that there are currently many different methods for early screening of colorectal cancer, but there is a lack of high-quality evidence
on which test is the best means of colorectal cancer screening.
Results from multiple randomized trials suggest that guaiac fecal occult blood test screening can reduce the relative risk
of colorectal cancer death by approximately 15% in the population.
However, this screening method has little or no effect
on the risk of colorectal cancer.

Many clinical experts believe that endoscopic screening may be more effective in preventing the occurrence
of colorectal cancer than fecal occult blood test.
Compared with fecal occult blood testing, endoscopic screening may be more effective in preventing colorectal cancer
.
The results of a pooled analysis study (including 3 randomized clinical trials) showed that the incidence of colorectal cancer was reduced by as much as 25%
after 10~12 years of follow-up of subjects who underwent sigmoidoscopy screening.

In addition, colonoscopy screening may be more effective than sigmoidoscopy because the endoscopist can view the entire colorectum in its entirety under a colonoscopic lens
.
As a result, sigmoidoscopy has largely been replaced
by colonoscopy.

It is important to note that colonoscopy screening is not yet widely available
globally due to the lack of sufficient evidence of benefit.
In addition, population participation remains suboptimal
due to the invasive nature of colonoscopy and the need for adequate bowel preparation.

Image source: 123RF

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
.

The results of the analysis showed that the proportion of participants screened (i.
e.
those included in the screening group and actually screened) varied from 33.
0% to 60.
7
% in different countries.
In general, the proportion of men is higher than that of women, and the proportion of elderly people is higher than that of young people
.

Sixty-two participants in the study (0.
5% of screened participants) were diagnosed with colorectal cancer
at screening.
In addition, 3634 participants (30.
7% of screened participants) had adenomas detected and removed
at screening.
A total of 15 participants (0.
13%) developed polypectomy-related major bleeding (all bleeding cases were treated endoscopically and no further intervention was required).

No participants had perforations or screening-related deaths
within 30 days of screening.

Overall, the 10-year risk of colorectal cancer was 0.
98% (259 cases) in the screening group and 1.
20% (622 cases) in the routine group, and the risk ratio (RR) of the two groups was 0.
82 (95% CI: 0.
70-0.
93).

This showed an 18% reduction in newly diagnosed cases of colorectal cancer in subjects screened for colonoscopy.

The analysis pointed out that a total of 455 patients (95% CI: 270-1429)
needed colonoscopy screening to prevent colorectal cancer within 10 years.
For subjects diagnosed with colorectal cancer with a known disease stage: 0.
38% and 0.
44% of participants in the screening group and the regular group were diagnosed with early (stage A or B) colorectal cancer, respectively, in addition, 0.
40% and 0.
50% of participants in the screening group and the regular group were diagnosed with advanced (stage C or D) colorectal cancer
.

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).

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.

In terms of all-cause mortality, 3036 participants (11.
03%) in the screening group died from any cause during the 10-year follow-up period, compared with 6079 participants (11.
04%) in the regular group who died from any cause (RR = 0.
99; 95% CI: 0.
96 to 1.
04).

The adjusted analysis showed that the risk of colorectal cancer would decrease from 1.
22% to 0.
84% after 10 years if all participants randomized to the screening group were actually screened (RR = 0.
69; 95% CI: 0.
55 to 0.
83).

In addition, participants in the screening group had a risk of dying from colorectal cancer of 0.
15% compared with 0.
30% in the usual group (RR = 0.
50; 95% CI: 0.
27 to 0.
77).

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 future, the researchers will continue to follow these subjects to see if the screening effect becomes more pronounced
over time.