Health utility for different health status.

Background
Adherence to colorectal cancer (CRC) screening remains suboptimal in many countries, reducing its cost-effectiveness. This study aimed to evaluate how multistage uptake rates influence the health benefit and cost-effectiveness of various CRC screening strategies in the Chinese population, incorporating both traditional and emerging screening methods.
Methods and findings
We developed a multistate Markov model (CRC-SIM) to evaluate the impact of multistep uptake on CRC screening. A hypothetical cohort of 100,000 individuals aged 40 was simulated and followed until 79 or death. Two-step screening strategies were modeled: initial screening followed by colonoscopy after a positive result. Traditional initial screening methods include: questionnaire-based risk assessment, fecal immunochemical test (FIT), and questionnaire combined with FIT; Non-invasive biomarker-based initial strategies include a hypothetical test meeting the minimum standards of China National Medical Products Administration (NMPAmin), multitarget stool DNA (mt-sDNA) test, and blood-based strategies. All strategies were modeled as one-time screenings, with outcomes projected for CRC cases, deaths, quality-adjusted life years (QALYs), and lifetime costs. Incremental cost-effectiveness ratios (ICERs) were calculated, and a cost-effectiveness heatmap was conducted to assess the impact of multistep uptake (modeled in 10% steps) on economic outcomes. All strategies reduced CRC cases, deaths and increased QALYs compared to no screening, with biomarker-based strategies outperforming the traditional methods at the same uptake level (e.g., questionnaire combined with FIT prevented 224 (95% confidence interval (CI) [157, 292]) CRC cases and 151 (95% CI [109, 195]) deaths, whereas NMPAmin prevented 312 (95% CI [257, 360]) cases and 210 (95% CI [175, 241]) deaths at 100% uptake). The cost-effectiveness heatmap indicated that each 10% increase in initial and follow-up colonoscopy uptake improved ICERs in a non-linear pattern. The questionnaire combined with FIT was the most cost-effective strategy (ICER = $2,413 per QALY gained). Non-invasive biomarker-based tests were not cost-effective compared with the combined questionnaire and FIT strategy under current assumptions of test costs and identical uptake rate. Threshold analysis showed that non-invasive biomarker-based screening would become cost-effective if test costs fell below $131.7 or colonoscopy uptake increased to at least 70% for NMPAmin and 50% for blood-based tests and mt-sDNA. Limitations include the assumption of a one-time screening scenario; future iterations of the model and merging evidence in repeated screening will address these limitations.
Conclusion
Improving screening participation could enhance health benefits and cost-efficiency in CRC screening. Questionnaire-based risk assessment combined with FIT was a cost-effective strategy in China, whereas non-invasive biomarker-based methods require cost reduction and higher uptake to justify adoption. These findings provide evidence for policymakers to optimize CRC screening programs.