Preplanned Studies: Evaluation of the Long-Term Benefits and Cost-Effectiveness of Colorectal Cancer Screening for Populations with Excess Weight — China, 2023

Introduction: Individuals with excess body weight have elevated colorectal cancer (CRC) risk. This study aimed to evaluate the long-term efficacy and cost-effectiveness of CRC screening strategies in populations with excess weight.

Methods: A multistate Markov model was used to evaluate the efficacy and cost-effectiveness of CRC screening. Three hypothetical cohorts were simulated based on body mass index (BMI) subgroups: normal, overweight, and obese. Screening strategies included colonoscopy (every 10 years) or an annual fecal immunochemical test, initiated at ages 45 and 50. Key outcomes included CRC cases, deaths, quality-adjusted life-year (QALY), lifetime costs, endoscopic resource use, and incremental cost-effectiveness ratios.

Results: QALY gains increased from 0.097 [95% confidence interval (CI): 0.091–0.102] in individuals with normal weight to 0.104 (0.101–0.107) in those who were overweight and 0.108 (0.105–0.111) in those who were obese. Individuals who were overweight or obese demonstrated 6%–14% greater colonoscopy efficiency compared with those of normal weight. All screening strategies were cost-effective (incremental cost-effectiveness ratio=USD 671–USD 949 per QALY gained), with a marginal decrease in cost per QALY gained observed at higher BMI. Despite improved cost-effectiveness, lifetime healthcare expenditures were higher in individuals who were overweight ($\text{\$} $845.19–$\text{\$} $955.00) and obese ($\text{\$} $1,358.00–$\text{\$} $1,467.37) than in those with normal weight ($\text{\$} $119.62–$\text{\$} $229.20).

Conclusion: CRC screening in China demonstrated effectiveness and cost-effectiveness across BMI groups, with populations with excess weight showing high colonoscopy resource efficiency. Amid rising lifetime healthcare costs attributable to high BMI, integrating weight management with CRC screening is critical for optimizing health and economic benefits.

Colorectal cancer (CRC) is the second most common cancer and the fourth leading cause of cancer-related deaths in China (1). Screening is an effective strategy for reducing both mortality and disease burden (2). Current screening guidelines primarily use age and family history of CRC as eligibility criteria, overlooking modifiable risk factors, such as being overweight or obese. This limitation may compromise the efficiency of CRC screening programs.

China is experiencing a sharp increase in obesity, with a relative increase of 144.2% from 1990 to 2021 (3), driven by rapid socioeconomic development and lifestyle changes. The country currently has the world’s largest population of individuals who are overweight or obese, and this trend is projected to impose an economic burden of CNY 418 billion by 2030 (3). As established independent risk factors for CRC, overweight and obesity contribute to 7.4% of the national CRC burden and represent the most financially burdensome among body mass index (BMI)-associated cancers (4). These findings highlight the urgent need for tailored CRC screening and management in individuals with excess weight.

Colonoscopy and fecal immunochemical testing (FIT) are the most widely used CRC screening modalities and are cost-effective in average-risk populations. While individuals with excess weight have a higher risk of CRC, they also face increased competing health risks and high medical costs, which may reduce the overall clinical and economic benefits of screening. Therefore, the long-term health outcomes and cost-effectiveness of CRC screening, specifically in populations with excess weight in China, remain unclear.

To address these gaps, we constructed a multistate Markov model to simulate the long-term health outcomes and cost-effectiveness of CRC screening strategies in populations with weight excess. This study provides policymakers with evidence to optimize screening programs and mitigate the rising burden of obesity-associated CRC.

Our validated CRC simulation model (CRC-SIM) reproduces the natural history, screening interventions, and clinical management of CRC. Nine health states were included: normal epithelium, non-advanced adenoma, advanced adenoma, CRC stages I–IV, and terminal states (CRC-related and other deaths), as detailed in Supplementary Figure S1. The model incorporated BMI-specific modifications for CRC risk, all-cause mortality, and obesity-associated costs.

We simulated three hypothetical population cohorts (N=100,000 per cohort), based on BMI strata: normal weight (18.5−23.9 kg/m²) and excess-weight populations (≥24 kg/m²). The excess-weight group was further divided into overweight (24−27.9 kg/m²) and obese (≥28 kg/m²) subgroups according to China’s BMI standards (5). All individuals entered the model at age 40 and were followed until age 79 or death, whichever occurred first. We modeled screening using colonoscopy (every 10 years) or annual FIT, initiated at ages 45 or 50.

A complete list of the variables and data sources used in our simulation model is provided in Supplementary Table S1. Transitional probabilities for natural history were derived from systematic reviews and calibrated to age-specific CRC incidence and mortality using the Global Burden of Disease data (https://ghdx.healthdata.org/). Health utilities were obtained from a cross-sectional study of 300 newly diagnosed patients with CRC in China, with utilities of 0.768, 0.655, 0.562, and 0.495 for CRC stages I through IV, respectively (6). Cost parameters included screening, clinical management, travel expenses, and productivity losses. The BMI-specific CRC risk was derived from a population-based CRC screening program in China (7). The association between BMI and overall mortality was derived from a large population-based cohort study of 3.6 million individuals (8). All risks were adjusted by the prevalence of overweight and obesity reported in the Report on the Nutrition and Chronic Diseases Status of Chinese Residents 2020, with relative risks for CRC incidence of 1.04 (overweight) and 1.12 (obesity) and for all-cause mortality of 1.05 (overweight) and 1.22 (obesity) (9). Additional healthcare costs associated with overweight and obesity were derived from a longitudinal study on individual healthcare expenditures, which estimated annual costs of $\text{\$} $44.02 for overweight and $\text{\$} $75.79 for obese individuals (10). All parameters were incorporated into our Markov models, in which individuals transitioned annually between exclusive health states. Health utilities and costs were assigned to each state to calculate QALYs and lifetime costs.

We estimated CRC cases, deaths, QALYs, lifetime costs, endoscopic resources, and incremental cost-effectiveness ratios per person, comparing each strategy with no screening. Cost-effectiveness was assessed against a willingness-to-pay threshold of US$\text{\$} $18,364/QALY. All costs were discounted by 5% annually according to the China Guidelines for Pharmacoeconomic Evaluations, with application of a half-cycle correction. Analyses were performed using R software (version 3.6.0; R Foundation for Statistical Computing, Vienna, Austria) and TreeAge Pro 2022 (TreeAge Software Inc., Williamstown, MA, USA).

Table 1 reveals distinct patterns in clinical outcomes across BMI categories (normal weight, overweight, and obese). In the absence of screening, CRC-specific mortality was higher among individuals who were overweight (2,420 deaths per 100,000) and obese (2,550 per 100,000) than among those with normal weight (2,264 per 100,000). Regarding health utility, individuals with obesity had the lowest overall QALYs [15.844, 95% confidence interval (CI): 15.841–15.847], followed by those who were overweight (16.016, 95% CI: 16.013–16.019) and those with normal weight (16.179, 95% CI: 16.176–16.182).

Screening significantly reduced CRC cases (59.40%–78.27%) and deaths (69.59%–81.63%) and increased QALYs gained (0.076–0.130) relative to no screening. The number of prevented CRC cases and deaths was comparable across BMI categories. Specifically, among individuals initiating colonoscopy at age 50, CRC case prevention rates were 74.53% for those with normal weight, 73.81% for those who were overweight, and 73.06% for those who were obese, with corresponding mortality reductions of 75.05%, 74.50%, and 74.08%, respectively. Concurrently, QALY gains increased from 0.0967 (95% CI: 0.091–0.102) in individuals with normal weight to 0.104 (0.101–0.107) in those who were overweight and 0.108 (0.105–0.111) in those who were obese. The disparity in QALY gains between higher-BMI and normal-weight groups widened when screening was initiated earlier (Table 1).

A high BMI was associated with improved colonoscopy efficiency. Compared with individuals with normal weight, those who were overweight and obese required fewer colonoscopies per case prevented (6%–8% and 10%–14%, respectively) and per death prevented (6%–8% and 10%–13%, respectively). This trend remained consistent across screening strategies and initiation ages (Table 2).

Both colonoscopy and FIT strategies were cost-effective (incremental cost-effectiveness ratio <$\text{\$} $18,364/QALY) across all BMI categories compared with no screening (Table 3). Most screening modalities showed progressively decreasing costs per QALY gained with increasing BMI ($\text{\$} $769, $\text{\$} $725, and $\text{\$} $703 per QALY gained for individuals with normal weight, overweight, and obesity, respectively, when initiated at age 50). Despite improved cost-effectiveness of screening, lifetime healthcare expenditures were higher in those who were overweight ($\text{\$} $845.19–$\text{\$} $955.00) and obese ($\text{\$} $1,358.00–$\text{\$} $1,467.37) than in those with normal weight ($\text{\$} $119.62–$\text{\$} $229.20) (Table 2).

We constructed a multistate Markov model to simulate the long-term health outcomes and cost-effectiveness of CRC screening in populations with excess weight. Our study demonstrates that CRC screening reduces both incidence and mortality across all BMI groups (normal weight, overweight, and obese) in China. Individuals who are overweight or obese derive greater QALY gains and resource efficiency (6%–13% fewer colonoscopies per CRC case and death prevented) than those with normal weight. Notably, most screening strategies proved to be cost-effective, with a marginal decrease in cost per QALY gained as BMI increased.

Few modeling studies have evaluated the cost-effectiveness of CRC screening across BMI groups. Our findings show that targeting populations with overweight or obesity yields greater QALY gains and improved cost-effectiveness compared with targeting populations with normal weight, consistent with results from a prior German modeling study (11). This enhanced benefit is likely owing to the high prevalence and faster progression of adenomas in individuals with a high BMI, which increases the yield of CRC screening. Our analysis further revealed that screening these populations also improves colonoscopy efficiency, requiring fewer procedures for CRC death prevention. These findings provide compelling evidence for prioritizing individuals with overweight or obesity in CRC screening programs in resource-limited settings.

A national screening study revealed significantly lower adherence to CRC screening among individuals with obesity (38.7% vs. 55.8% among those with normal weight) (12). This reduced uptake persisted despite free colonoscopic access [odds ratio (OR)=2.16] (13). Insufficient risk awareness may have contributed to this disparity. Additionally, individuals with a high BMI incur substantially higher lifetime healthcare expenditures than those with normal weight, primarily because of obesity-related comorbidity management. These results underscore the critical need to integrate BMI management into the CRC screening continuum to optimize health and economic benefits.

The strengths of our study include: (1) a comprehensive evaluation incorporating CRC risk, competing comorbidities, and obesity-attributable costs; (2) assessment of multiple screening initiation ages to address the rising burden of early-onset CRC; and (3) estimation of resource demand and costs, providing essential evidence for resource-limited regions. Importantly, our model was specifically adapted to reflect the distinct epidemiological patterns of CRC and obesity in China, thereby generating tailored, policy-relevant evidence.

This study has at least three limitations. First, it primarily relied on the adenoma–carcinoma sequence (70%–90% of CRC cases) because of insufficient Chinese data on serrated pathways. Second, we did not consider emerging screening technologies (including mt-sDNA) owing to the lack of population-based evidence in China. Future evaluations should include novel technologies when Chinese-specific data become available. Finally, more effective obesity markers (including central adiposity metrics) should be incorporated to optimize obesity-specific risk stratification.

Our study highlights that CRC screening in China is cost-effective across BMI groups, with individuals who are overweight or obese showing high colonoscopy resource efficiency. Based on these results, we recommend that screening programs in China prioritize populations with a high BMI, particularly under resource constraints. Furthermore, amid rising healthcare costs caused by obesity and related comorbidities, integrating weight management into CRC screening is essential for optimizing screening efficacy and long-term cost containment.