Colorectal Cancer Risk With Negative Colonoscopy or Nonadherence After Positive FOBT Screening

Importance Population-based colorectal cancer (CRC) screening programs are implemented globally. When determining screening intervals, variations in the risk of subsequent CRC by colonoscopy outcome should be considered. Objective To evaluate the incidence of CRC after a negative screening colonoscopy result or nonadherence to colonoscopy in individuals with a positive fecal occult blood test (FOBT) result. Design, Setting, and Participants This was a prospective cohort study conducted between January 1, 2008, and December 31, 2021. It was conducted within a population-based CRC screening program in the Stockholm-Gotland region, Sweden, using biennial FOBT as the primary screening test in the target population aged 60 to 69 years. The study cohort included all men and women born between 1938 and 1954 residing in the Stockholm-Gotland region between 2008 and 2012 who were invited to a CRC screening. All participants with a positive FOBT result were identified. Data provided by national registers were analyzed from October 2024 through January 2026. Exposures Individuals with a positive FOBT result were categorized as (1) having a negative result on recommended follow-up colonoscopy or (2) nonadherence to recommended follow-up colonoscopy. Main Outcomes and Measures The primary outcome was CRC incidence compared with the general population (defined as all individuals in the cohort who were invited to screening, excluding those with negative colonoscopy or nonadherence following positive FOBT). This was measured by standardized incidence ratio (SIR). Results Of 318 096 individuals invited to CRC screening with FOBT, 14 873 had a positive FOBT result (7799 male 52.4%; median IQR age, 65 63-67 years). Of these individuals, 11 473 (87.3%) underwent a colonoscopy, and 8433 of those colonoscopies (73.5%) were negative. Individuals with a negative screening colonoscopy result had a significantly lower observed CRC incidence (SIR, 0.52; 95% CI, 0.39-0.68) relative to the general population, with a lower SIR in men (0.37; 95% CI, 0.25-0.56) than women (0.71; 95% CI, 0.49-1.03). In contrast, individuals with a positive FOBT who did not adhere to follow-up colonoscopy had a markedly increased CRC incidence (SIR, 4.21; 95% CI, 3.24-5.48) compared with the general population. Conclusions and Relevance In this study, a decrease in CRC incidence was observed among individuals with negative results in screening colonoscopies, with a greater decrease in men, supporting risk-based, individualized follow-up strategies. A high-risk group for CRC was identified among individuals who did not adhere to follow-up colonoscopy, enabling targeted interventions to improve early CRC detection.