Development and External Validation of a TNM plus CEA Nomogram for Overall Survival after Surgery in Early-Onset Colorectal Cancer

Abstract Background : Early-onset colorectal cancer (EOCRC) requires postoperative prognostic tools that add clinically useful information beyond anatomic stage while remaining transparent enough for external use. We developed and externally validated a parsimonious overall-survival (OS) nomogram for surgically treated EOCRC and assessed the incremental value of pretreatment carcinoembryonic antigen (CEA). Methods : SEER patients diagnosed from 2011 to 2015 were assigned to development and internal validation cohorts, and patients treated at the Second Affiliated Hospital of Harbin Medical University from 2014 to 2017 formed an external validation cohort. Candidate predictors were screened with LASSO Cox regression. LASSO-selected models were evaluated using nested model comparison, proportional-hazards diagnostics, a grade-stratified sensitivity model, Harrell's C-index, time-dependent AUC, calibration, decision curve analysis, and Kaplan-Meier risk stratification. Results : The analysis included 7164 patients, including 3447 in development, 3446 in internal validation, and 271 in external validation. LASSO retained tumor grade, AJCC T, AJCC N, AJCC M, and CEA. The grade-containing model fitted better but violated the global proportional-hazards assumption; therefore, the primary model retained AJCC T/N/M and CEA, with grade handled in sensitivity analysis. C-indexes were 0.813, 0.805, and 0.700 in the three cohorts. External 1-, 3-, and 5-year AUCs were 0.604, 0.705, and 0.726. Conclusions : This externally validated TNM plus CEA nomogram provides a simple risk-stratification tool for OS after surgery in EOCRC. Absolute long-term predictions should be interpreted cautiously in external settings.