Colonoscopy may reduce the risk of dying of colorectal cancer by as much as 50%, but there’s a catch: It only works if you get the scan.
That’s the big takeaway message from the first randomized trial of colonoscopy, published Sunday in The New England Journal of Medicine.
Colonoscopy has been recommended as a screening test for adults age 50 and over since the mid-1990s, and some 15 million colonoscopies are performed in the United States each year. This recommendation has been based on evidence from observational studies that looked back in time to compare how often colorectal cancer is diagnosed in people who received colonoscopies versus those who did not. These studies can be subject to bias, however, so scientists look to randomized trials that blindly sort people into two groups: those who are assigned to get an intervention, and those who are not. These studies then follow both groups forward in time to see if there are differences. Those studies have been difficult to do for colon cancer, which can be slow growing and may take years to be diagnosed.
The NordICC study, which stands for Northern-European Initiative on Colon Cancer, included more 84,000 men and women ages 55 to 64 from Poland, Norway and Sweden. None had gotten a colonoscopy before. The participants were randomly invited to have a screening colonoscopy between June 2009 and June 2014, or they were followed for the study without getting screened.
In the 10 years after enrollment, the group invited to get colonoscopies had an 18% lower risk of colorectal cancers than the group that wasn’t screened. Overall, the group invited to screening also had a small reduction in their risk of death from colorectal cancer, but that difference was not statistically significant – meaning it could be simple due to chance.
The researchers say they’re going to continue to follow participants for another five years. It could be that because colon cancers can be slow-growing, more time will help refine their results and may show bigger benefits for colonoscopy screening.
Normally, those kinds of disappointing results from such a large, strong study would be considered definitive enough to change medical practice.
But there’s a big caveat in this study that limits how the results should be applied: Only 42% of the participants who were invited to get a colonoscopy went through with it.
“I think it’s just hard to know the value of a screening test when the majority of people in the screening didn’t get it done,” said Dr. William Dahut, chief scientific officer at the American Cancer Society, who was not involved in the study.
When the study authors restricted the results to the people who actually received colonoscopies – about 12,000 out of the more than 28,000 who were invited to do so – the procedure was found to be more effective. It reduced the risk of colorectal cancer by 31% and cut the risk of dying of that cancer by 50%.
Experts say it’s difficult to rely just on the results from this subgroup, however, because they can be subject to bias.
For example, in clinical trials, researchers often worry about the “healthy volunteer effect”: People who volunteer for testing may be more likely to take care of themselves by eating a healthy diet or doing other things that can’t be measured by the study that might reduce their risk.
Dr. Michael Bretthauer, a researcher on the study who leads the clinical effectiveness group at the University of Oslo in Norway, says that as a gastroenterologist, he found the results disappointing.
But as a researcher, he has to follow the science, “so I think we have to embrace it,” he said.
“And we may have oversold the message for the last 10 years or so, and we have to wind it back a little,” he said.
Bretthauer thinks of the full set of study results – including the people who didn’t get a colonoscopy – to be the minimal amount of benefit a person could expect to get, while the more narrow results – limited to the subset of people who did get colonoscopies – are the largest benefits people could expect.
Based on his results, then, he expects that screening colonoscopy probably reduces a person’s chances of colorectal cancer by 18% to 31%, and their risk of death from 0% to as much as 50%, “which is on the low end what what I think everybody thought it would be.”
Other studies have estimated larger benefits for colonoscopies, reporting that these procedures could reduce the risk of dying of colorectal cancer by as much as 68%.
There are other caveats that may limit the applicability of the study’s results.
First, says Dr. Douglas Corley, a gastroenterologist who directs delivery science and applied research at Kaiser Permanente Northern California, it’s not clear how much followup people got after their colonoscopies. Part of the value of the screening comes from close followup if abnormalities are detected, he said.
Corley, who was not involved in the study, also says colonoscopies have gotten better since the research was conducted. The technology is better, and so is the training doctors get to perform them, so the findings may not be a reflection of the performance of screening tests available today.
The question of the most effective way to screen for colon cancer is an important one.
Colorectal cancer was the fourth most common cause of cancer in the United States in 2022 and the second most common cause of cancer death, according to the National Cancer Institute.
Several other studies now in the works may help settle the question of how effectively colonoscopies catch cancer. One, Colonprev, is being conducted in Spain; another is based in the United States and called Confirm. The Spanish study finished its followup of patients in late 2021. he US trial is following patients until 2027.
Dr. Jason Dominitz is the national director of gastroenterology for the Veterans Health Administration. He’s running the Confirm study, which is comparing colonoscopy to the fecal immunochemical test, or FIT, which looks for problems by detecting blood in stool.
Dominitz co-authored an editorial that was published alongside the new study Sunday in The New England Journal of Medicine and says no one should cancel their colonoscopy based on these results.
“We know that colon cancer screening works,” he told CNN. Previous studies of FIT and a test called sigmoidoscopy, which looks only at the lower part of the colon, have been shown to reduce both cancer incidence and colorectal cancer deaths.
“Those other tests work through colonoscopy,” Dominitz said. “They identify people at high risk who would benefit from colonoscopy, then the colonoscopy is done and removes polyps, for example, that prevents the individual from getting colon cancer in the first place, or it identifies colon cancer at a treatable stage.”
Polyps are benign growths that can turn into cancers. They are typically removed when identified during a screening colonoscopy, which can lower a person’s risk of colorectal cancer in the future.
Dominitz said this randomized controlled trial was a test of advice as much as it was a test of the value of colonoscopy.
“If you ask the population to do something, how much of an impact will it have?” he said.
Overall, the study found that just inviting people to get a colonoscopy didn’t have a large beneficial impact across these countries, partly because so many people didn’t do it.
Dominitz thinks the low participation can be partly explained by the study’s setting. Colonoscopies are not as common in the countries involved in the study as they are in the United States. In Norway, he says, official colorectal cancer screening recommendations didn’t come until this past year.
“They don’t see the public service announcements. They don’t hear Katie Couric talking about getting screened for colon cancer. They don’t see the billboards in the airport and whatnot,” he said. “So an invitation to be screened in Europe is, I think, likely to be somewhat different than an invitation to be screened in the US.”
In the US, according to data from the US Centers for Disease Control and Prevention, about 1 in 5 adults between the ages of 50 and 75 have never been screened for colorectal cancer.
The US Preventive Services Task Force says a variety of methods and regimens work to detect colorectal cancer. It recommends screening with tests that check for blood and/or cancer cells in stool every one to three years, a CT scan of the colon every five years, a flexible sigmoidoscopy every five years, a flexible sigmoidoscopy every 10 years paired with stool tests to check for blood annually, or a colonoscopy every 10 years.
In 2021, the task force lowered the recommended age to start routine screening for colorectal cancer from 50 to 45 because the cancer is becoming more common in younger adults.
In considering which screening test might be best for his patients, Dominitz says, he remembers the advice from a mentor who said, “The best test is the one that gets done.”
As proof, he points to early results from a large randomized trial from Sweden that’s testing colonoscopy, FIT testing and no screening at all.
Results collected from more than 278,000 people enrolled between March 2014 and the end of 2020 found that 35% of the group assigned to get a colonoscopy actually got one, compared with 55% who were assigned to the FIT stool test group.
To date, slightly more cancers have been detected in the group assigned to stool testing than in the group assigned to get a colonoscopy – “so participation with screening really is key!” Domintz said.