Objective: To estimate the cost-effectiveness of esophageal cancer endoscopic screening once-in-a-lifetime and to predict the optimal screening age for people in high-risk areas of rural China.

Methods: A Markov model was constructed to predict and compare the effect of four esophageal cancer endoscopic screening modalities which varied with different screening ages. Long-term epidemiological effectiveness and cost-effectiveness were predicted by simulation of the model.

Results: Compared with the control group, strategies starting at 40, 45, 50 and 55 year-old had saved life-years of 629.51, 769.88, 738.98 and 533.21 years per 100 000 people, respectively, of which the strategy starting at 45 year-old saved the maximum life years. All strategies were cost-effective and starting at 40 year-old cost the most per life-year saved. Among all alternatives, strategies starting age at 45 year-old and 50 year-old were incremental cost-effective, and the incremental cost-effective ratios were 34 962.87 and 3 346.43 RMB per life year saved, respectively.

Conclusions: The strategy starting at 40 year-old implemented at present and other strategies were cost-effective in high-risk areas of rural China. However, the 45-year-old group is more aligned with the principle of cost-effectiveness. Considering the cost-effectiveness of different strategies and social economic status, 45 year-old is regarded as the optimal starting age of esophageal cancer once-in-a-lifetime endoscopic screening and is recommended in areas lacking health resources. The strategy of starting age at 40 year-old which could obtain better screening effects would be preferable in wealthy regions.

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