Exploratory Development and Interpretation of an Internally Validated XGBoost-Cox Model Based on Preoperative...

Background: Patients with stage I rectal cancer generally have favorable outcomes after curative surgery, but prognosis is not completely homogeneous. This study explored the prognostic association of preoperative inflammation-nutrition indices with overall survival and developed an interpretable internally validated machine learning survival model. Methods: We retrospectively included 475 patients with primary pathological stage I rectal adenocarcinoma who underwent curative-intent radical surgery at Sichuan University West China Hospital between 2018 and 2021. Patients downstaged to ypStage I after neoadjuvant therapy or treated by local transanal excision without lymph node dissection were excluded. Candidate predictors included age, sex, carcinoembryonic antigen, and routinely available preoperative inflammation-nutrition indices. LASSO-Cox regression was used for feature selection. Six survival models were developed and evaluated using 1000 bootstrap resamples with out-of-bag internal validation. Model performance was assessed at 60 months using time-dependent AUC, C-index, Brier score, calibration, and decision curve analysis. SHAP analysis was used for model interpretation. Results: During a median follow-up of 68 months, 30 deaths occurred. LASSO-Cox regression identified five predictors: age, lymphocyte-to-white blood cell ratio, fibrinogen-to-lymphocyte ratio, albumin-to-alkaline phosphatase ratio, and neutrophil-to-HDL cholesterol ratio. In bootstrap out-of-bag internal validation, XGBoost-Cox achieved the highest, although only marginally higher, discriminative performance among the evaluated models, with a 60-month time-dependent AUC of 0.783, a C-index of 0.774, and a Brier score of 0.0507. The calibration intercept and slope of XGBoost-Cox were 0.519 and 1.070, respectively. SHAP analysis identified age as the most influential predictor, followed by the selected inflammation-nutrition indices. Decision curve analysis suggested potential clinical utility within threshold probabilities from 1% to 20%, although this finding remains exploratory. Conclusions: Preoperative inflammation-nutrition indices may contribute to overall survival prognostic stratification in primary pathological stage I rectal cancer. External validation in larger multicenter cohorts is required before clinical application.