Background
Gastric cancer continues to be a major global health threat, having accounted for 0.8 million deaths and 19.1 million disability-adjusted life-years (DALYs) in 2017 [
1]. Results from a recent meta-analysis, which demonstrated a 40% reduction in risk of death from gastric cancer with endoscopic screening [
2], shed light on the opportunity to reduce the burden of gastric cancer through effective screening policy. With the third-highest rate of gastric cancer incidence globally [
3], Japan introduced a national endoscopic screening program in 2015, offering biennial and triennial endoscopic screening for people older than 50 years [
4]. Understanding the trade-offs in lifetime benefits and costs of current screening guidelines, as opposed to alternative screening strategies, at the population level is a vital input into dialogues on cancer control policy. However, with a paucity of empirical evidence and longitudinal data, the lifetime cost-effectiveness of population-wide screening strategies with different screening intervals at various starting and stopping ages remains unclear.
To inform screening policy in a timely fashion, microsimulation decision models can estimate the long-term consequences of a large number of potential policies that are not routinely examined in empirical studies [
5,
6]. Here, to identify which strategies might deliver cost-effective care, we developed a microsimulation model which incorporates the best available data to estimate the lifetime cost-effectiveness of various national endoscopic screening scenarios while accounting for individual-level heterogeneity in gastric cancer risk.
Discussion
We developed a well-calibrated and validated microsimulation model to simulate an average-risk population over the lifetime course under 15 unique screening scenarios. Comprehensive modeling showed that the current national endoscopic screening program in Japan is unlikely to be cost-effective. In contrast, a more favorable option would be triennial endoscopic screening of individuals aged 50 to 75 years. This would result in an estimated 27.2 QALYs gained per 1000 individuals and a reduction in the lifetime risk of gastric cancer mortality by 63% with a corresponding ICER of $45,665.
The present study highlights several important policy questions. To date, no recommended age for endoscopic screening cessation has been available. However, with the population aging rapidly, Japan is likely to experience an increased demand for cancer screening despite limited resources. Comprehensive examination of the added value of extending screening practices in older populations is clearly paramount. Our modeling results demonstrate that the benefits of continuing endoscopic screening in people beyond age 75 years do not justify the additional endoscopic screenings performed, owing to diminishing returns. In terms of competing causes of death, adverse events caused by screening, and reduced eligibility for curative surgery in older individuals, determining whether to screen individuals aged over 75 years should be done on an individualized basis, such as with regard to individual risk profile, previous screening history, and the individual’s values and preferences. Further research to explore optimal screening strategies at higher age limits is warranted.
In this analysis, the efficient frontier was dominated by strategies which initiated endoscopic screening at age 50 years; these provided a more favorable option in terms of cost-effectiveness. Our results are in line with the gastric cancer burden in Japan. Data from the population-based cancer registry revealed that the age-specific incidence rate among people aged 40 to 49 years (10.4 per 100,000) was lower than that in people aged 50 to 59 years (65.8 per 100,000) in 2014 [
12]. Gastric cancer incidence in these two populations has declined steadily over the past two decades, with reductions in men and women since 1993 of 62.8% and 51.3% at 40 to 49 years compared with 35.8% and 33.4% at 50 to 59 years, respectively (Additional file
1: Figure S7) [
12]. For screening effectiveness, age-specific analysis from the Korean national cancer screening program demonstrated that endoscopic screening is related to reduced risk of gastric cancer mortality in the population aged 40 to 74 years [
73]. The burden of disease and screening effectiveness, together with the modeling results, indicated that initiating screening at the age of 50 years would be a reasonable option.
To our knowledge, this is the first study to use microsimulation decision modeling to comprehensively project the lifetime cost-effectiveness of national gastric cancer control measures in a high-incidence setting. The strength of this study is that a comprehensive approach was used during formulation of the microsimulation model. This approach incorporated detailed gastric cancer natural history findings and the impact of dynamic individual risk profiles on disease progression by synthesizing the best available data from nationally representative surveys and meta-analyses. This model generates population-level estimates that can hardly be achieved by simpler models, since it also preserves individual-level heterogeneity. In addition, it has been extensively calibrated to the nationally representative observed data. Validation analyses across the period 1994 to 2013 have shown that the secular trends of model predictions are consistent with the observed mortality data. We rigorously modeled 15 clinically relevant scenarios to explore potential lifetime effects across the endoscopic screening spectrum. Further, comprehensive sensitivity analyses were performed, adding robustness to the efficient frontier in this study.
Our study also has several limitations. First, the model assumed full adherence with screening and diagnostic evaluations for all strategies. The current analysis was designed to inform population guidelines; therefore, this assumption allowed the model to predict the maximum achievable benefit of a public health action. Furthermore, to facilitate comparisons, all screening scenarios were based on an identical assumption. Second, because this study focused on current policy and its alternatives, we did not evaluate risk stratification approaches to gastric cancer screening. The combination test of serum pepsinogen and
H. pylori antibody has been proposed to be a potential tool for predicting gastric cancer development [
74‐
76]. However, the specificity for both single and combination tests of serum pepsinogen and
H. pylori antibody was shown to be low in one population-based cohort study in Japan [
77]. In the future, given that the predictive accuracy of biomarkers could be improved, the risk stratification approach remains a future opportunity which may lead to further enhancement of the cost-effectiveness in a gastric cancer screening context. Lastly, since costs were Japan-based, it is unclear how generalizable our cost efficacy results are to other healthcare systems. However, we have provided both the health benefits and number of endoscopies needed, which are more likely to be generalizable.
Acknowledgements
The views expressed in this paper are solely those of the authors. Hsi-Lan Huang and Chi Yan Leung had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Kota Katanoda received grants from JMWH Bayer (2016 fiscal year). Eiko Saito received grants from Pfizer Health Research Foundation. The funders of the study had no role in the study design, data collection, data analysis, data interpretation, or writing of the report.
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