Cost-Effectiveness of Initiating Colorectal Cancer Screening at Age 40 Among Average-Risk Individuals in China

China recently updated its colorectal cancer (CRC) screening guidelines, lowering the recommended initiation age from 45 to 40 years for the general population in response to the rising burden and earlier onset. This study evaluates the cost-effectiveness of earlier initiation and identifies the optimal screening strategy. A Markov model was developed to compare 48 screening strategies, combining different starting ages, methods (fecal immunochemical test [FIT], multitarget stool DNA [MT-sDNA] test, methylated Septin 9 [mSEPT9] test, computed tomography colonography [CTC], or colonoscopy), and frequencies, from the healthcare system perspective. Incremental cost-effectiveness ratios (ICERs) were calculated based on quality-adjusted life-years (QALYs), with willingness-to-pay thresholds set at one- and three-time China's per-capita gross domestic product (GDP). The results show that all screening strategies are cost-effective compared with non-screening under the three-time GDP threshold, with nearly half found to be cost-saving. Starting annual FIT screening at age 40 is the most cost-effective under both thresholds, with an ICER of US$5381/QALY and reductions of 5.5% in CRC cases and 7.4% in CRC-related deaths compared with the second-best strategy of starting at age 45. Starting 10-yearly colonoscopy screening at age 40 may be optimal, but only under very low thresholds. Both MT-sDNA and mSEPT9 tests would become the optimal options only if their costs were substantially reduced. The findings are highly robust across sensitivity analyses. This study supports the updated recommendation to lower the CRC screening initiation age for average-risk individuals and identifies annual FIT screening as the optimal strategy in the current context of China.