Fecal Occult Blood Screening Outcomes Adjusted for Contamination Bias and Nonadherence
Johannes Blom, Lennarth Nyström, Håkan JonssonImportance
Population-based colorectal cancer (CRC) screening with fecal occult blood tests (FOBT) is widely implemented. Estimating associations of invitation to and participation in the screening program with CRC mortality is challenging due to lack of valid control groups and uncertainties about optimal follow-up time.
Objective
To estimate associations of invitation to and participation in screening with CRC mortality reduction when adjusting death from CRC diagnosed more than 2 years after cessation of screening and nonadherence.
Design, Setting, and Participants
This prospective cohort study was conducted in the Stockholm-Gotland region of Sweden between 2008 and 2021. Yearly birth cohorts of individuals aged 60 to 69 years (born 1938-1954) were randomly assigned to a study group (SG) invited to screen between 2008 and 2012 or to a control group (CG) who were either invited to screen between 2013 and 2015 or were not invited to screen. Analyses were performed between May 2024 and February 2026.
Exposure
Invitation to and participation in CRC screening, adjusting for contamination in the SG (exposed), invitations in the CG (not exposed), and nonadherence.
Main Outcome and Measures
CRC-specific mortality, defined as CRC in the Cancer Register (2008-2020) or the Swedish Quality Register for Colorectal Cancer (2021), with CRC as underlying cause of death in the Cause of Death Register. Poisson regression was used to estimate mortality rate ratios (RRs) with 95% CIs, adjusting for follow-up year, attained age at follow-up, contamination from CRC deaths diagnosed more than 2 years after screening in the SG, invitations in the CG, and nonadherence.
Results
The study included 376 511 individuals, with 203 692 in the SG (99 472 men [48.8%]; mean [SD] age at start of follow-up, 63.6 [3.2] years) and 172 819 in the CG (84 705 men [49.0%]; mean [SD] age at start of follow-up, 62.8 [3.5] years). During follow-up, 856 CRC deaths occurred in the SG and 812 CRC deaths occurred in the CG. After adjustment for CRC deaths diagnosed more than 2 years after the last SG invitation (455 deaths) and invitations in the CG (166 deaths), the RR was 0.74 (95% CI, 0.58-0.94), a 26% reduction. After further adjustment for nonadherence in the SG (196 deaths) and participation in the CG (82 deaths), the RR for participation was 0.57 (95% CI, 0.40-0.80), a 43% reduction.
Conclusions and Relevance
In this cohort study of population-based FOBT screening, screening invitation was associated with a 26% reduction in CRC mortality and participation was associated with a 43% reduction, after accounting for contamination and nonadherence. These findings suggest that bias adjustment is important when evaluating screening programs, and these findings support efforts to increase screening uptake.