Great links! I’m in the trenches cranking out the GI referrals, fast track colonoscopies, and Cologaurd orders, consistent with current guidelines. Glad to see that on a larger scale people are listening.
I went back and listened to a podcast (Freakonomics MD) about this trial, and they actually predicted the increase in colonoscopies... more about this study generating patient interest and discussion with doctors. Really an excellent breakdown, including the principal investigator from Norway being interviewed:
I've thought a lot about this study and enjoyed a Sensible Medicine podcast on it featuring Prasad and Mandrola coming in negative on colonoscopies and Adam Cifu, an internist, still supporting them as the superior tool. The NordICC trial was of course in a population which has not been brain-washed into thinking that going through a test requiring propofol anesthesia and a prep that not uncommonly results in syncope and arrhythmias so there was. low uptake after an invitation. Makes you understand why intention to treat is the usual method of RCT analysis.
I thought that trial was kind of bizarre (invited vs not invited?!) and although it looked at mortality, I don’t think it smashed the previous studies which overall show various benefits of colonoscopy / CRC. Cologuard has done a good marketing job I guess, and we use it preferentially over FIT as an institution based on trials/data. Anecdotally I have picked up 2 cancers in early stages using cologaurd recently.
This is from behind the paywall at NEJM journal watch re: Nordic:
Colonoscopy Screening for Colorectal Cancer: A Randomized Trial
Allan S. Brett, MD, reviewing Bretthauer M et al. N Engl J Med 2022 Oct 9
Screening didn't lower mortality in a primary analysis, but that's not the end of the story.
No large randomized, controlled trials have been conducted to examine mortality outcomes from colonoscopy screening for colorectal cancer (CRC) — until now. In this study, 85,000 previously unscreened people (age range, 55–64) in Norway, Poland, and Sweden were randomized in a 1:2 ratio to receive an invitation to undergo colonoscopy screening, or to receive no invitation.
Only 42% of people in the invited group accepted their invitations and underwent colonoscopy; those with polyps had subsequent surveillance at standard intervals. The primary intent-to-screen analysis (which includes all invited people, whether or not they followed through with colonoscopy) revealed the following outcomes at 10 years:
Cumulative incidence of CRC was significantly lower in the invited group (0.98% vs. 1.20%), likely due to removal of precancerous polyps.
CRC-related mortality at 10 years was not significantly different in the two groups (0.28% vs. 0.31%).
All-cause mortality at 10 years was identical in the two groups (11.0%).
Among nearly 12,000 screening colonoscopies, no perforations and 15 cases of major bleeding were reported.
In a secondary adjusted per-protocol analysis — a comparison of people who actually underwent screening versus controls — a difference in CRC-related mortality reached significance (0.15% vs. 0.30%). This “best-case” outcome would translate to roughly 1 fewer CRC death per 700 screened people.
COMMENT
These results are not straightforward; hence, they probably won't change the general U.S. preference for colonoscopy to screen for CRC. Editorialists consider the primary findings — a small relative reduction in CRC risk and no reduction in CRC-related mortality — as “surprising and disappointing.” Results of the per-protocol analysis, which includes only the minority of invited people who actually underwent colonoscopy but introduces bias that randomization was designed to eliminate, are somewhat more compelling. Moreover, longer follow-up might yield a larger survival benefit. Additional randomized trials to compare colonoscopy and no screening probably won't be done, but large trials comparing colonoscopy and fecal immunochemical testing are in progress.
Great links! I’m in the trenches cranking out the GI referrals, fast track colonoscopies, and Cologaurd orders, consistent with current guidelines. Glad to see that on a larger scale people are listening.
I'm intrigued by the bump in CRC screening in the younger group. Are you more likely to choose a non-colonoscopy screening tool since publication of the NordICC trial last year?(https://open.substack.com/pub/sensiblemed/p/screening-colonoscopy-misses-the?r=1f2oz2&utm_campaign=post&utm_medium=email). Are you choosing Cologuard over FIT testing?
I went back and listened to a podcast (Freakonomics MD) about this trial, and they actually predicted the increase in colonoscopies... more about this study generating patient interest and discussion with doctors. Really an excellent breakdown, including the principal investigator from Norway being interviewed:
https://freakonomics.com/podcast/should-you-bother-getting-a-colonoscopy/
I've thought a lot about this study and enjoyed a Sensible Medicine podcast on it featuring Prasad and Mandrola coming in negative on colonoscopies and Adam Cifu, an internist, still supporting them as the superior tool. The NordICC trial was of course in a population which has not been brain-washed into thinking that going through a test requiring propofol anesthesia and a prep that not uncommonly results in syncope and arrhythmias so there was. low uptake after an invitation. Makes you understand why intention to treat is the usual method of RCT analysis.
TSC -- I'll plead ignorance since I only care for tiny adults. Thanks for your contribution, Ryan.. Interesting insight!
I thought that trial was kind of bizarre (invited vs not invited?!) and although it looked at mortality, I don’t think it smashed the previous studies which overall show various benefits of colonoscopy / CRC. Cologuard has done a good marketing job I guess, and we use it preferentially over FIT as an institution based on trials/data. Anecdotally I have picked up 2 cancers in early stages using cologaurd recently.
This is from behind the paywall at NEJM journal watch re: Nordic:
Colonoscopy Screening for Colorectal Cancer: A Randomized Trial
Allan S. Brett, MD, reviewing Bretthauer M et al. N Engl J Med 2022 Oct 9
Screening didn't lower mortality in a primary analysis, but that's not the end of the story.
No large randomized, controlled trials have been conducted to examine mortality outcomes from colonoscopy screening for colorectal cancer (CRC) — until now. In this study, 85,000 previously unscreened people (age range, 55–64) in Norway, Poland, and Sweden were randomized in a 1:2 ratio to receive an invitation to undergo colonoscopy screening, or to receive no invitation.
Only 42% of people in the invited group accepted their invitations and underwent colonoscopy; those with polyps had subsequent surveillance at standard intervals. The primary intent-to-screen analysis (which includes all invited people, whether or not they followed through with colonoscopy) revealed the following outcomes at 10 years:
Cumulative incidence of CRC was significantly lower in the invited group (0.98% vs. 1.20%), likely due to removal of precancerous polyps.
CRC-related mortality at 10 years was not significantly different in the two groups (0.28% vs. 0.31%).
All-cause mortality at 10 years was identical in the two groups (11.0%).
Among nearly 12,000 screening colonoscopies, no perforations and 15 cases of major bleeding were reported.
In a secondary adjusted per-protocol analysis — a comparison of people who actually underwent screening versus controls — a difference in CRC-related mortality reached significance (0.15% vs. 0.30%). This “best-case” outcome would translate to roughly 1 fewer CRC death per 700 screened people.
COMMENT
These results are not straightforward; hence, they probably won't change the general U.S. preference for colonoscopy to screen for CRC. Editorialists consider the primary findings — a small relative reduction in CRC risk and no reduction in CRC-related mortality — as “surprising and disappointing.” Results of the per-protocol analysis, which includes only the minority of invited people who actually underwent colonoscopy but introduces bias that randomization was designed to eliminate, are somewhat more compelling. Moreover, longer follow-up might yield a larger survival benefit. Additional randomized trials to compare colonoscopy and no screening probably won't be done, but large trials comparing colonoscopy and fecal immunochemical testing are in progress.