Management after a positive fecal immunochemical test and a nonexplanatory colonoscopy: a scoping review and practical decision framework

Background: In fecal immunochemical test (FIT)-based colorectal cancer (CRC) screening, colonoscopy after a positive FIT often identifies no CRC or advanced neoplasia, leaving management poorly standardized. We mapped evidence on definitions, extracolonic evaluation, colonoscopy quality, residual CRC risk, and screening re-entry after a positive FIT and nonexplanatory colonoscopy. Methods: This registered scoping review followed PRISMA-ScR guidance. PubMed/MEDLINE, Scopus, and Web of Science were searched until April 2026, along with reference-list screening and targeted searching of official screening program/policy documents. Sources were charted by one reviewer; included sources, uncertain eligibility decisions, and key findings underwent second-reviewer verification. Results: We included 10 studies on definitions, 11 empirical studies plus three contextual evidence syntheses on evaluation beyond the colon, 11 core empirical studies on colonoscopy quality/residual CRC risk, and nine empirical studies on management and screening re-entry, supplemented by policy mapping. Definitions varied substantially, supporting "nonexplanatory colonoscopy" as a pragmatic umbrella term. Routine upper gastrointestinal or small-bowel evaluation was not supported in otherwise asymptomatic individuals. Reassurance was quality dependent; residual CRC risk was low in the short term, but not zero. Screening re-entry pathways varied and were not evidence based. Conclusions: Management should first be to establish whether the index colonoscopy is reliable enough to justify reassurance. After a trusted negative examination, the evidence does not support routine upper gastrointestinal or small-bowel evaluation, or routine early repeat colonoscopy in otherwise asymptomatic individuals. Residual CRC risk remains low but not zero, and optimal screening re-entry remains uncertain.