Cancer
Evaluating the Effect of Continued FIT Screening: A Target Trial Emulation Using the Clone–Censor–Weight Method Buket Öztürk Esen* Buket Öztürk Esen Esen Department of Clinical Epidemiology, Aarhus University
Background: The effectiveness of the fecal immunochemical test (FIT) in reducing colorectal cancer (CRC) mortality is well-known. However, studies evaluating the effect of attending a second FIT screening following a negative initial result remain limited.
Objective: To evaluate the effect of attending a second FIT screening on CRC-specific mortality and CRC diagnosis risk among individuals with an initial negative FIT.
Methods: We conducted a cohort study of 622,265 individuals with an initial negative FIT. We used an emulated trial design with clone–censor–weight (CCW) methodology to compare two screening strategies: 1) attending a second FIT screening, versus 2) not attending a second FIT screening.
Results: At 6-year follow-up, the risk of CRC-specific mortality was 0.07% (95% CI: 0.06%; 0.08%) for those attending a second FIT screening versus 0.17% (95% CI: 0.14%; 0.21%) for those not attending. This resulted in a relative risk (RR) of 0.39 (95% CI: 0.30; 0.52) and a risk difference (RD) of -0.10% (95% CI: -0.14%; -0.07%). For CRC diagnosis, the 6-year risk was 0.63% (95% CI: 0.61%; 0.66%) in the attendance group versus 0.66% (95% CI: 0.59%; 0.74%) in the non-attendance group, yielding an RR of 0.96 (95% CI: 0.85; 1.08) and an RD of -0.03% (95% CI: -0.11%; 0.05%).
Conclusion: Participation in a second FIT screening following an initial negative result reduces the relative risk of CRC-specific mortality. However, even though the RR is large, the RD is small. Furthermore, despite the use of the CCW method to mitigate bias, residual selection bias due to unmeasured factors cannot be ruled out. This indicates that while the intervention is effective in relative terms, the absolute benefit is small due to the low baseline risk in the years immediately following a negative FIT, which may inform discussions on optimal screening intervals.