Evidence Trace, complete trial record
In plain terms
In plain terms: Sigmoidoscopy and colonoscopy screening for colorectal cancer has strong evidence from human clinical trials. The benefit shown in those trials is if that describes your situation.
Sigmoidoscopy and colonoscopy screening for colorectal cancer
A
Replicated: replicated trials on a qualifying endpoint
The endpoint this grade is based on: Hard clinical endpoint (mortality, major event)
The evidence as the record states it
Sigmoidoscopy: Juul et al. (Ann Intern Med, 2022; PMID 36215714) pooled 4 randomized trials, 274,952 adults aged 55 to 64 in Norway, the US, the UK and Italy; after 15 years colorectal cancer deaths were 20% lower (rate ratio 0.80, 0.72 to 0.88), 0.13 fewer deaths per 100 people invited, and cases 21% lower; women benefited less than men. The trials: PLCO (Schoen et al., N Engl J Med, 2012; PMID 22612596), deaths 26% lower; NORCCAP (Holme et al., JAMA, 2014; PMID 25117129), hazard ratio 0.73; UKFSST (Atkin et al., Lancet, 2017; PMID 28236467), protection lasting at least 17 years; SCORE (Segnan et al., J Natl Cancer Inst, 2011; PMID 21852264), deaths 22% lower, not significant by intention to screen. Colonoscopy: NordICC (Bretthauer et al., N Engl J Med, 2022; PMID 36214590), 84,585 adults aged 55 to 64 in Poland, Norway and Sweden, one invitation to colonoscopy against usual care, 42.0% of those invited attended; at 10 years colorectal cancer was diagnosed in 0.98% against 1.20% (risk ratio 0.82, 0.70 to 0.93) and deaths from it were 0.28% against 0.31% (0.90, 0.64 to 1.16); death from any cause 11.03% against 11.04%. Lifetime: Bretthauer et al. (JAMA Intern Med, 2023; PMID 37639247) pooled randomized screening trials with more than 9 years of follow-up and found sigmoidoscopy the only test with a significant gain in lifetime, 110 days (0 to 274), and colonoscopy 37 days (-146 to 146). NordICC was funded by the Research Council of Norway and others.
PMID 36215714 PMID 22612596 PMID 25117129 PMID 28236467 PMID 21852264 PMID 36214590 PMID 37639247
Evidence by specific use
Colorectal cancer deaths, an invitation to flexible sigmoidoscopy, adults aged 55 to 64
Grade A
Juul et al. (Ann Intern Med, 2022; PMID 36215714) pooled the four trials: after 15 years, 0.13 fewer colorectal cancer deaths per 100 people invited (rate ratio 0.80, 0.72 to 0.88), about 1 death prevented for every 770 invited (worked out by EBL from the 0.13 per 100), with less benefit in women than in men. Each trial was run by a different national group: PLCO in the US (PMID 22612596), NORCCAP in Norway (PMID 25117129), UKFSST in the UK (PMID 28236467) and SCORE in Italy (PMID 21852264). A hard outcome replicated across independent groups: A.
PMID 36215714 PMID 22612596 PMID 25117129 PMID 28236467 PMID 21852264
Colorectal cancer diagnoses, an invitation to screening colonoscopy, adults aged 55 to 64
Grade C
NordICC (Bretthauer et al., N Engl J Med, 2022; PMID 36214590): colorectal cancer was diagnosed in 0.98% of those invited against 1.20% with usual care at 10 years (risk ratio 0.82, 0.70 to 0.93); 455 people had to be invited to prevent one case. One trial, not yet repeated: C under Rule 06.
PMID 36214590
Colorectal cancer deaths and death from any cause, an invitation to screening colonoscopy, adults aged 55 to 64
Grade D
NordICC (PMID 36214590): deaths from colorectal cancer were 0.28% against 0.31% (risk ratio 0.90, 0.64 to 1.16) and deaths from any cause 11.03% against 11.04%, neither significantly different at 10 years. A pooled analysis of screening trials estimated 37 days of lifetime gained with colonoscopy, not significant (Bretthauer et al., 2023; PMID 37639247). With fewer than half attending and 10 years of follow-up, the trial may have been too short or too diluted to show a death benefit; that is a reason for the 15-year result, not a reason to grade above D now.
PMID 36214590 PMID 37639247
Why Grade A and not higher
Grade A requires a hard clinical endpoint or objectively measured functional outcome, independently replicated across at least two trials. Sigmoidoscopy and colonoscopy screening for colorectal cancer meets that standard based on the trials cited above. A downgrade to Grade B would follow if replication attempts produced null results, if the effect size proved substantially smaller in a broader population, or if the studied dose proved impractical to sustain.
What this grade covers and what it does not
Grade A on deaths from colorectal cancer after an invitation to sigmoidoscopy: four independent population trials, pooled to a 20% reduction at 15 years (PMID 36215714), a hard outcome replicated across groups. Grade C on colorectal cancer diagnoses after an invitation to colonoscopy: one trial, an 18% reduction at 10 years (NordICC; PMID 36214590), not yet repeated (Rule 06). Grade D, tested, on colorectal cancer deaths and on death from any cause after an invitation to colonoscopy: NordICC found neither significantly lower at 10 years (PMID 36214590), with 42% attendance; its 15-year results are not yet published. WHAT THIS GRADE DOES NOT COVER: people who attended rather than everyone invited, which the trials report only as adjusted estimates; stool tests, graded on their own record; and people with symptoms or a family history, who were not the population studied.
What would move this grade
A null result in a well-powered independent replication trial, or evidence that the effect does not hold at a practically sustainable dose, would prompt downgrade to Grade B.
How to track whether this is working
Measured in the trials: colorectal cancer diagnoses and deaths from colorectal cancer in national registries, counted for everyone invited, whether or not they attended.