Navigating false-positive outcomes after stool-based colorectal cancer screening tests: a scoping review

For patients undergoing colorectal cancer screening with stool-based tests followed by a negative colonoscopy, management can be challenging due to potential concern for upper aerodigestive cancer or extra-colonic cancer. We sought to synthesize contemporary clinical approaches and cancer outcomes following a positive stool test and a negative colonoscopy and to identify areas in need of further research.

Because of the heterogeneity of published research and available evidence, we conducted a scoping review of English-language, peer-reviewed, and full-text articles through September 2025. Two independent reviewers screened titles and abstracts followed by full text assessment, and data extraction. Data were synthesized thematically to explore the outcomes and work-up strategies associated with false-positive results in FIT and mt-sDNA tests within the context of extra-colonic cancer screening.

Of 3442 studies identified, 49 underwent full text review of which 8 met inclusion criteria. Most patients were female and ≥50 years; however, reporting of demographic information was variable. The brand of stool-test, definition of stool-test positivity, definition of negative colonoscopy, and follow-up time were variably reported and defined. In terms of outcome, ~0.5% of patients had CRC on second colonoscopy. Incidence of non-colorectal aerodigestive or upper GI cancer ranged from 0-4.3%.

There is a critical need for a standardized reporting framework among studies evaluating outcomes after positive stool-test and negative colonoscopy to better synthesize across studies and ultimately, improve clinical management.