Benefits of colorectal cancer screening using fecal immunochemical testing with varying positivity thresholds by age and sex

Abstract

Background: Fecal immunochemical test (FIT) performance for colorectal cancer screening varies by age and sex, yet most FIT-based screening programs use uniform positivity thresholds. This study assessed the potential benefits of stratifying FIT thresholds based on age and sex.

Methods: We conducted a meta-analysis of FIT sensitivity and specificity at various positivity thresholds by age and sex. We then used these estimates in 2 microsimulation models of colorectal cancer and projected lifetime clinical outcomes, incremental costs, and quality-adjusted life-years (QALYs) gained from age- and sex-stratified FIT strategies. FIT thresholds ranged from 10 to 50 µg hemoglobin per gram of feces.

Results: For current uniform FIT screening (20 µg hemoglobin/gram of feces), models projected 85.67 to 122.15 QALYs gained at incremental costs of ‒$982 to $504 per 1000 individuals compared with no screening. At equivalent costs to current uniform screening, only 1 model found stratified FIT approaches cost-effective, yielding a marginal increase of 1.04 and 1.10 QALYs gained/1000 female and male individuals, respectively. At a willingness-to-pay threshold of $100 000/QALYs gained, both models found stratified FIT cutoffs to be the best strategy, with cutoffs being equal to or higher for males and lowest at older ages (70-75 years). Uniform strategies showed comparable effectiveness, falling within 1 quality-adjusted life-day per person of efficient strategies at up to $112 more per person. Results were sensitive to FIT test performance characteristics and 1-time setup costs.

Conclusion: Stratifying FIT thresholds by age and sex may be cost-effective compared to current screening. The gain in expected health benefits with stratified FIT screening, however, is likely small.

Figure 1.

Colorectal cancer natural history and screening effects simulated by the Microsimulation Screening Analysis–Colon Model and the Simulation Model of Colorectal Cancer.

Figure 2.

Costs and QALYs gained for all FIT threshold combinations, by model and sex. Strategies are labeled “X/Y/Z,” where X, Y, and Z represent thresholds in μg hemoglobin per gram of feces for ages 45-59 years, 60-70 years, and 70-75 years, respectively. The blue diamond marks the current uniform FIT threshold of 20 µg hemoglobin per gram of feces, which is the reference strategy. FIT = fecal immunochemical test; MISCAN-Colon = Microsimulation Screening Analysis–Colon; QALY = quality-adjusted life-year; SimCRC = Simulation Model of Colorectal Cancer.

Figure 3.

Expected loss per individual for all FIT threshold combinations. Strategies are labeled “X/Y/Z,” where X, Y, and Z represent thresholds in μg hemoglobin per gram of feces for ages 45-59 years, 60-70 years, and 70-75 years, respectively. The colored lines represent strategies that minimize the expected loss for some value of the willingness-to-pay threshold. The black dotted line represents the current uniform threshold of 20 µg hemoglobin per gram of feces. FIT = fecal immunochemical test; MISCAN-Colon = Microsimulation Screening Analysis–Colon; QALY = quality-adjusted life-year; SimCRC = Simulation Model of Colorectal Cancer.