Background
There is growing evidence that the balance between harms and benefits of colorectal cancer (CRC) screening can be improved using risk stratification. Previous studies have shown that prior fecal hemoglobin (f-Hb) concentrations determined by fecal immunochemical testing (FIT), have greater predictive power than age and sex for the detection of CRC in the next screening round.

Methods
We used the MISCAN-Colon microsimulation model to assess the costs, benefits and harms of risk-stratified screening intervals based on prior f-Hb concentrations of negative FITs. A novel module simulating quantitative f-Hb concentration was integrated into MISCAN-Colon and calibrated using data from the Dutch national screening program between 2014-2020. We categorized individuals into three distinct risk groups based on their prior negative FIT result: low risk (0 micrograms (μg) f-Hb per gram), intermediate risk (>0-15 μg f-Hb/g), and high risk (>15-<47 μg Hb/g). We evaluated different invitation intervals, ranging from 0.5 to 4 years for each risk category, and compared the cost-effectiveness with that of uniform screening strategies. We focused specifically on two risk-stratified screening strategies: (1) minimizing costs while ensuring that the number of Quality-Adjusted Life Years (QALYs) are at least as high as those for uniform biennial screening, and (2) maximizing QALYs while keeping costs below the level of uniform biennial screening. Additionally, we conducted a threshold analysis to evaluate the impact of adherence on the cost-effectiveness.

Results
Risk-stratified screening strategies based on prior f-Hb concentrations were cost-effective compared to uniform screening. At the same costs as uniform biennial screening, the number of QALYs gained would increase up to 8.8%. In this strategy, low-risk individuals were invited biennially, while the intermediate- and high-risk group were invited every 6 months. For similar QALYs as the uniform biennial screening, the costs would reduce with 15.4%, inviting the low-risk group every 2.5 years, the intermediate-risk group annually and the high-risk group every 6 months. If the adherence to risk-stratified screening would drop by more than 7.5% compared to uniform screening, then risk-stratified intervals were no longer cost-effective.

Conclusion
This study highlights the potential of risk-stratified CRC screening intervals based on prior f-Hb concentrations to enhance the trade-off between screening harms and benefits. However, it is crucial to ensure that the transition from uniform to risk-stratified screening will not negatively impact the adherence to CRC screening.

Table 1 Outcomes per 1,000 individuals of two risk-stratified screening strategies, the current uniform biennial screening strategy and the no screening strategy. All strategies are compared to no screening. The strategy name represents the screening intervals for individuals in different risk groups: the first, second and third number correspond to the low-, intermediate-, and high-risk group, respectively. FIT: faecal immunochemical test, CRC: colorectal cancer, QALY: quality-adjusted life year.

Table 2 Outcomes per 1,000 individuals of two risk-stratified screening strategies and the current uniform biennial screening strategy for different adherence rates. The green (red) cells indicate less (more) costs or more (less) QALYs for the risk-stratified screening strategy compared to biennial screening. Costs and QALYs are compared to no screening. The strategy names represent the screening intervals for individuals in different risk groups: the first, second and third number correspond to the low-, intermediate-, and high-risk group, respectively. QALY: quality-adjusted life year

Danica van den Berg

Appearances