Early results from a European trial of colonoscopy has two important lessons for the practice, which has been widely embraced in the United States.
The lessons from the NordICC study, preliminary results on practical points of performing colonoscopy, were published online May 23 in JAMA Internal Medicine. (However, data on the primary end points of colorectal cancer mortality and incidence will not be available for another 8 years or so.)
The study showed that colonoscopy could be performed successfully without sedation, and that insufflation with carbon dioxide rather than air could significantly reduce postprocedure abdominal pain.
Both of these findings could lead to changes in the way that colonoscopy is performed in the United States, said an expert. “This is an important study because there are no randomized clinical trials showing the effects of colonoscopy and its implications,” David Lieberman, MD, professor of medicine and chief of the division of gastroenterology, Oregon Health & Science University, Portland, told Medscape Medical News.
Dr Lieberman authored an invited commentary linked to the NordICC Study and is himself one of the authors of a consensus document on guidelines for colonoscopy surveillance after screening and polypectomy (Gastroenterology. 2012;143:844-857).
The NordICC Study
The study involved 94,959 patients identified as eligible from population registries in Norway, Poland, Sweden, and the Netherlands; of these, 94,394 patients were randomized to the screening group (n = 31,420) and the control group (n = 62,974).
Patients received a personal letter of invitation and information about the study. Screenings were done across 5 years — between 2009 and 2014. Colonoscopy and bowel preparation were provided without cost.
Trial endoscopists had to have performed at least 300 endoscopies before the study and were required to have a workload of 200 colonoscopies a year.
Standard video colonoscopies were used. Centers were encouraged, but not required, to use carbon dioxide insufflation.
All lesions detected were removed during colonoscopy where possible; biopsies were undertaken on all tumors. Dedicated pathologists categorized polyps (adenomas, serrated, inflammatory, neuroendocrine, and others) on the basis of World Health Organization classifications.
Abdominal pain was assessed during and 24 hours after the procedure using a validated patient questionnaire, scoring pain from 1 (none) to 4 (severe).
NordICC Study Results
Participation rate was 40% and varied between countries (Norway, 61%; Sweden, 40%; Poland 33%; and the Netherlands, 23%).
Sedation administration also varied (Norway, 11%; Poland, 23%; Sweden, 46%; and the Netherlands, 90%). The overall cecum intubation rate was 97% and median withdrawal time was 10 minutes, although this was highly variable among endoscopists.
Of 62 (0.5%) individuals diagnosed with colon cancer, 14 (0.1%) had tumors in the proximal colon and 50 (0.4%) had tumors in the distal colon. The overall polyp prevalence was 48.0% — 31.0% with adenomas (10.4% high risk); 24.6% of individuals were diagnosed with serrated polyps, with 2.3% with a size of at least 10 mm
“Some patients who develop colorectal cancer within 5 years after a prior colonoscopy have genetic characteristics of serrated polyps, which tend to be found on the right side of the colon,” Dr Lieberman said. “We now have new information about the expected rates of serrated polyps, which may be helpful in developing future benchmarks for detection,” he commented.
During colonoscopy, no pain was reported by 46% of individuals, slight pain by 34%, moderate or severe pain by 13%, and severe pain by 8%. Pain during colonoscopy was not associated with sedation (adjusted odd ratio, 0.91; 95% confidence interval, 0.61 – 1.35); intercountry differences related to variations in clinical practice were reported.
No difference in pain during the procedure was reported, regardless of insufflation gases used in the procedure — air or carbon dioxide. However, during the 24 hours after colonoscopy, pain was reported by four times as many patients who received air insufflation as patients who received carbon dioxide (17.0% vs 4.0%; P < .001); severe pain was also experienced by more patients who received air (5.6% vs 1.0%).
One patient experienced colonoscopy perforation, two experienced postpolypectomy serosal burns, which resolved, 18 developed bleeding due to polypectomy (and were treated endoscopically), and 51 experienced minor vasovagal reactions.
Lessons to Be Learned
Corresponding author Michael Bretthauer, MD, from the Department of Health Management and Health Economics, University of Oslo, Norway, told Medscape Medical News that there were several features about the study that have implications for undertaking screening in the population at large. “This study shows how colonoscopy performs if you invite individuals directly from population registries,” he said.
He pointed out that the design allows a more valid evaluation of colonoscopy because it bypasses the self-selection bias seen in most studies in the United States, which enroll patients who have indicated an interest in screening before randomization. He cited the Prostate, Lung, Colorectal, and Ovarian Screening trial as an example of a large American screening trial.
“We believe that the data from the NordICC study will mimic more closely what can be expected in the real world when screening is implemented in a population,” he said.
Lessons for the United States
For the United States, where screening colonoscopy is widely adopted, data from the NordICC study provide evidence that challenges current practices, Dr Lieberman suggested.
Endoscopist variability: Variability among participating endoscopists was also an important quality measure reported in the study. Cecum intubation rate and adenoma detection rates determine quality, Dr Lieberman explained. “The researchers have to be commended for this. Prior studies did not consider quality as an important variable,” Dr Lieberman told Medscape Medical News. “A lower-quality colonoscopy is associated with a greater risk for cancer in subsequent years,” he said.
“Training for doctors in endoscopy has not been standardized until very recently,” Dr Bretthauer said. There is no reason to believe that the variability across endoscopists is different in the United States, he pointed out. In the United States, colonoscopy is undertaken by gastroenterologists, surgeons, and family physicians, and the standards of training differ, Dr Lieberman indicated.
Dr Bretthauer explained that audits and credentialing have been lacking. “Efforts have now started in some countries (the UK is doing most here) to do this, in recognition of the large variability in performance,” he said.
Participation rate: The adherence or participation rate was unexpected. “A colonoscopy program depends on participation, and adherence of 40% is disappointing, especially when the procedure was offered at no charge at a convenient location to participants,” Dr Lieberman commented. “Obviously, the nonparticipants will derive no benefit, and it remains to be seen if this level of participation would result in better outcomes than a FIT program with better adherence,” he added.
Dr Lieberman noted that the recruitment methods were different across countries, and Norway, which chose to recruit via a telephone call, had the highest participation rate. “If we had a perfect screening test that could reduce death from colorectal cancer, it would still only work if patients choose to undergo it,” he writes in his commentary.
“Participation may be primarily a matter of awareness and modifiable by education,” Dr Bretthauer said.
Use of sedation: The results from the NordICC study suggest that sedation during colonoscopy is not necessary, Dr Bretthauer explained. It does not affect patient pain and discomfort, he pointed out “Thus, the US approach with heavy sedation during colonoscopy is questioned. It increases costs and complication rates,” he said.
Dr Lieberman agreed. The practice arose to make patients more comfortable about the procedure, he explained. Patients receive conscious sedation (where they can be aroused) or deep sedation (where they cannot be aroused), he pointed out.
Perhaps we need to rethink the role of sedation for colonoscopy.
“In the US, we are moving toward deep sedation with propofol and anesthesia support. It adds cost and may add risk, too,” he told Medscape Medical News. “It appears that patient tolerance of colonoscopy screening was quite acceptable without sedation in most cases. Perhaps we need to rethink the role of sedation for colonoscopy and use deep sedation selectively,” he writes.
Abdominal pain and CO₂ insufflation: Dr Bretthauer explained that a considerable proportion of patients have abdominal pain for up to 24 hours after colonoscopy. This pain lasts longer than the pain one may experience during the procedure and affects patients. “This is often not communicated to patients,” he said.
“The NordICC study shows that carbon dioxide insufflation rather the standard air, which is used in most hospitals in the US, reduces pain after colonoscopy dramatically,” he added.
With clear evidence that use of CO₂ insufflation reduces postprocedure discomfort, all endoscopy units should adopt this procedure.
Dr Lieberman endorses this approach. “With clear evidence that use of CO₂ insufflation reduces postprocedure discomfort, all endoscopy units should adopt this procedure,” he states in his commentary.
Embraced in the United States, Not Elsewhere
Colonoscopy screening has been widely embraced in United States but not yet elsewhere in the world, mainly because clinical trial evidence is lacking.
“Colonoscopy screening is not widespread in other countries because there are no randomized trials performed on colonoscopy screening and its effectiveness on colorectal cancer incidence or mortality,” Dr Bretthauer commented to Medscape Medical News.
“Most countries require such evidence before implementing screening, as in any other area in medicine,” he added. “Imagine a drug being marketed without a clinical trial; it would never happen,” he said.
Dr Lieberman explained that the practice has been adopted in the United States on the basis of cohort and case–control studies, not evidence from randomized studies in colonoscopy. He also indicated that sigmoidoscopy studies, where only one-third of the lower colon is visualized, showed a lower incidence of colon cancer mortality.
“Some experts have proposed that, if sigmoidoscopy is effective, complete colonoscopy might be more effective, not only for early detection of colorectal cancer, but for cancer prevention by removal of precancerous polyps,” Dr Lieberman stated. “Virtually all health organizations and many governments now endorse colorectal cancer screening,” he said.
JAMA Intern Med. Published online May 23, 2016