Absolute Risk Prediction for Esophageal Squamous Cell Carcinoma Adaptable to Regional Disease Burden across Diverse Regions.

Background: Esophageal squamous cell carcinoma (ESCC) exhibits a long latency period and has a significant geographic disparity in incidence, which underscores the need for models predicting the long-term absolute risk adaptable to the regional disease burden.

Methods: A total of 31,883 participants in a large-scale population-based screening trial (Hua County, China) were enrolled to develop the model. Severe dysplasia and above cases identified at screening or follow-up were defined as the outcome. We calculated the absolute risk in three steps: (i) constructing a relative risk model using logistic regression, (ii) calculating the age-specific baseline hazard, and (iii) adjusting for the competing risk of all-cause death excluding ESCC. Flexible incidence rate parameters were integrated into the model to ensure its relevance across diverse regions worldwide.

Results: A total of 295 severe dysplasia and above cases were detected. The relative risk model consisted of old age, male gender, an irregular meal pattern, a preference for hot or hard food, a BMI of less than 22 kg/m2, and ESCC family history. The AUC was 0.753 (95% confidence interval, 0.749-0.757). The averaged 5-and 10-year absolute risk were 0.53% and 1.30% among participants. Based on our model, we developed an online calculator and incorporated flexible incidence rate parameters, demonstrating ideal risk stratification tailored to regions with varying disease burdens (https://pkugenetics.shinyapps.io/escc_risk_prediction/).

Conclusions: We developed an absolute risk model to predict individualized long-term risk of ESCC, accounting for the local disease burden.

Impact: This model has the potential to mitigate the global burden of ESCC by enabling targeted screening and personalized prevention strategies.