Development and validation of a clinically interpretable risk scoring system for predicting one-year all-cause...

The conventional American Joint Committee on Cancer (AJCC) staging system primarily relies on anatomical features and may not capture multidimensional prognostic factors, limiting individualized prediction of one-year mortality in esophageal cancer. We developed and internally validated a Surveillance, Epidemiology, and End Results (SEER)-based, clinically interpretable risk score and quantified its incremental value beyond AJCC staging, accompanied by an online calculator.

We identified patients with esophageal cancer diagnosed between 2004 and 2022 from the SEER database and defined one-year all-cause mortality as the endpoint. The cohort was randomly split into development and validation sets (7:3), stratified by the outcome. Candidate predictors were explored using univariable analyses and selected using least absolute shrinkage and selection operator (LASSO) logistic regression with cross-validation. A multivariable logistic model was fitted, and coefficients were scaled to derive an integer-based score; performance loss due to discretization/rounding was assessed. Model performance was evaluated using area under the receiver operating characteristic curve (AUC), Brier score, calibration intercept/slope, Hosmer-Lemeshow test, standardized mortality ratio, and decision curve analysis. Incremental value beyond AJCC staging was assessed using DeLong's test, net reclassification improvement (NRI) and integrated discrimination improvement (IDI).

A total of 20,056 patients were included, with a one-year mortality rate of 45.14%. The final model incorporated staging information, treatment variables (surgery, chemotherapy), and clinicopathologic factors (age, sex, grade, tumor size, histology, tumor site), as well as diagnosis-to-treatment interval, which may partially reflect triage-related factors. The risk score achieved an AUC of 0.778 [95% confidence interval (CI): 0.766-0.790] in the validation cohort, outperforming the AJCC combined stage model (AUC 0.709; P<0.001). Calibration was good (Brier score 0.190; Hosmer-Lemeshow P=0.40), with no evidence of systematic calibration drift across prespecified demographic, clinicopathologic, tumor-site, and surgical-status subgroups. Compared with AJCC staging, the score improved reclassification (NRI 0.258; IDI 0.110) and provided stable net benefit across threshold probabilities of 0.25-0.75. Score-defined strata also showed persistent gradients in three- and five-year cumulative all-cause mortality. Notably, it revealed marked within-stage heterogeneity in AJCC Stage III, distinguishing groups with observed one-year mortality of 16.4% versus 91.4%. An interactive online calculator and a bedside scorecard were developed for clinical use.

This SEER-based risk score provides robust discrimination, good calibration, and clinical utility, and may serve as an early-course adjunctive tool for short-term risk refinement beyond AJCC staging.