Evidence Trace, complete trial record
In plain terms
In plain terms: Stool-based colorectal screening (gFOBT and FIT) has strong evidence from human clinical trials. The benefit shown in those trials is if that describes your situation.
Stool-based colorectal screening (gFOBT and FIT)
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
Graded by test, because the randomized mortality evidence and the test most people actually use are not the same thing. Shaukat et al. (New England Journal of Medicine, 2013; PMID 24047060): 30-year follow-up of the Minnesota randomized screening trial, colorectal-cancer mortality reduced by 32 percent, using GUAIAC FOBT. Kaneko et al. (Therapeutic Advances in Gastroenterology, 2026; PMID 42254696): systematic review and network meta-analysis of nine randomized trials at about 10 years. On intention to treat, gFOBT reduced colorectal-cancer mortality (RR 0.87, 95% CI 0.79 to 0.95) and FIT did not, with the FIT evidence described as limited. No strategy reduced all-cause mortality. Doubeni et al. (JAMA Network Open, 2024; PMID 39028667) is the FIT-specific evidence EBL cites and it is a nested case-control study, not a randomized trial. The Grade A therefore belongs to gFOBT and to stool-based screening as a strategy. It does not transfer to FIT on the strength of a shared detection principle. Castells et al. (Lancet, 2025; PMID 40158525) reported COLONPREV's 10-year mortality endpoint: FIT was non-inferior to colonoscopy, which is graded separately below at C, a single trial. Non-inferiority against an active comparator is not evidence of a reduction against no screening.
PMID 24047060 PMID 42254696 PMID 39028667 PMID 40158525 PMID 22356323
Evidence by specific use
Colorectal cancer mortality, guaiac FOBT (gFOBT)
Grade A
Randomized, replicated, on a hard clinical endpoint. Shaukat et al. (New England Journal of Medicine, 2013; PMID 24047060), the 30-year Minnesota follow-up, reported a 32 percent reduction in colorectal-cancer mortality with guaiac FOBT. Kaneko et al. (Therapeutic Advances in Gastroenterology, 2026; PMID 42254696), a network meta-analysis of nine randomized trials, found gFOBT reduced colorectal-cancer mortality on intention to treat, RR 0.87 (95% CI 0.79 to 0.95). Neither found a reduction in all-cause mortality.
PMID 24047060 PMID 42254696
Colorectal cancer mortality, fecal immunochemical test (FIT) specifically
Grade D
This letter is about the evidence, not about the test. FIT detects human hemoglobin specifically and outperforms guaiac FOBT on sensitivity and specificity, and it is the stool test in routine use. What is missing is randomized evidence that FIT itself reduces colorectal-cancer mortality. Kaneko et al. (Therapeutic Advances in Gastroenterology, 2026; PMID 42254696) found the reduction for flexible sigmoidoscopy and for guaiac FOBT and not for FIT, and described the FIT evidence as limited. Doubeni et al. (JAMA Network Open, 2024; PMID 39028667), the FIT-specific study EBL cites, is a nested case-control design, not a randomized trial. Grade D here means the randomized evidence for this test on this endpoint has not been produced. It is not a finding that FIT failed.
PMID 39028667 PMID 42254696
Colorectal cancer mortality versus colonoscopy
Grade C
Castells et al. (Lancet, 2025; PMID 40158525), COLONPREV: a pragmatic randomized non-inferiority trial in 57,404 adults aged 50 to 69. Invitation to biennial FIT was non-inferior to invitation to one-time colonoscopy for colorectal-cancer mortality at 10 years, 60 deaths against 55, risk difference -0.02 percent (95% CI -0.10 to 0.06). Participation was higher in the FIT arm. A single trial that no one has repeated is C under the written rule, however large; it was held at B until the replication search of October 2026 confirmed that no second trial has reported. It answers a different question from the row above: non-inferior to colonoscopy is not the same claim as reduces mortality against no screening, and this trial had no unscreened arm. Quintero et al. (New England Journal of Medicine, 2012; PMID 22356323) is the same trial's baseline report, before the mortality endpoint matured.
PMID 40158525 PMID 22356323
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. Stool-based colorectal screening (gFOBT and FIT) 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 by the hard-outcome route: colorectal-cancer mortality in a randomized screening trial with thirty years of follow-up, plus a network meta-analysis of nine randomized trials. WHAT THIS GRADE DOES NOT COVER, AND THIS IS THE WHOLE POINT OF GRADING BY TEST: the randomized mortality evidence is for GUAIAC FOBT. The test most people are actually handed is FIT, and on intention to treat FIT did not reduce colorectal-cancer mortality in that same analysis, with its evidence described as limited. FIT therefore sits at D on this record and the A does not transfer to it on the strength of a shared detection principle. Neither test reduced all-cause mortality in any strategy. And non-inferiority against colonoscopy, which is graded separately at C as a single unreplicated trial, is not evidence of a reduction against no screening at all.
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
A stool FIT test annually starting at age 45, or as directed by your physician if family history indicates earlier screening. A positive FIT result requires colonoscopy follow-up within 60 days: FIT is a screening tool, not a diagnostic one. Completion dates and results; consistency of annual testing is the primary performance measure.