Age‐Dependent Prognostic Significance of Preoperative Transthyretin After Curative Resection for Stage I– <scp>III</scp> Colorectal Cancer

ABSTRACT Background Preoperative malnutrition and systemic inflammation are established determinants of adverse outcomes in colorectal cancer (CRC). Transthyretin (TTR), a rapid‐turnover hepatic protein, reflects both nutritional and inflammatory status; however, its clinical utility may be influenced by age‐ and sex‐related variability. This study evaluated the prognostic significance of preoperative TTR in patients undergoing curative resection for stage I–III CRC. Methods A retrospective cohort of 536 patients who underwent curative resection for stage I–III CRC between 2014 and 2024 at a single institution was analyzed. Sex‐specific TTR cutoffs were derived using survival classification and regression tree analysis (20.9 mg/dL for men; 16.95 mg/dL for women), and patients were stratified into low‐ and high‐TTR groups. The primary endpoint was recurrence‐free survival (RFS). Survival outcomes were assessed using Kaplan–Meier analysis, multivariable Cox proportional hazards modeling, and age‐stratified analyses. Results Preoperative TTR levels were lower in women and demonstrated a progressive decline with increasing age. Patients with low TTR exhibited significantly inferior RFS compared with those with high TTR (log‐rank p < 0.0001). In multivariable analysis, low preoperative TTR remained an independent predictor of worse RFS (HR 2.407, 95% CI 1.625–3.566; p < 0.001). Age‐stratified analyses demonstrated that the prognostic impact of low TTR was most pronounced in younger patients and progressively attenuated with advancing age. Conclusions Preoperative TTR represents an independent prognostic biomarker following curative resection for stage I–III CRC. Its prognostic utility is age‐dependent, with greatest relevance in younger patients, supporting interpretation within an age‐ and sex‐specific framework.