Abstract
Background: Patients with colorectal cancer (CRC) have varying responses to 5-fluorouracil (5-FU) treatment, particularly reduced-dose regimens. Inflammatory and tumor-associated serum biomarkers, such as carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), and cancer antigen 125, may refine prognostic assessment. However, their combined performance in patients with CRC receiving reduced-dose 5-FU remains understudied. This retrospective study evaluated the prognostic value of multiple biomarkers in these patients, aiming to identify optimal combinations for personalized therapeutic strategies and improved clinical outcomes. Methods: Data (2017-2023) on patients' clinicopathological characteristics and pretreatment serum biomarker levels were collected from a medical center in central Taiwan. Dose classification followed institutional standards. Reduced-dose chemotherapy was confirmed from patients' medical records. Intergroup comparisons, receiver operating characteristic curve analysis, logistic regression, Cox proportional hazards modeling, and survival analysis were performed. Furthermore, a multivariate prognostic nomogram was constructed. Results: The study cohort comprised 95 patients receiving reduced-dose 5-FU. Univariate analyses highlighted cigarette smoking, advanced stage, poor tumor differentiation, and elevated pretreatment CEA level as significant predictors of mortality. Multivariate analysis indicated tumor differentiation grade and pretreatment CEA level as significant independent predictors. Cancer antigen 125, CEA, and CA19-9 exhibited robust discriminatory performance. The multivariate nomogram exhibited acceptable discrimination. Conclusions: Tumor differentiation, disease stage, and pretreatment CEA level emerged as independent predictors of overall survival in patients with CRC receiving reduced-dose 5-FU. Serum biomarkers, particularly CEA and CA19-9, may be included in comprehensive prognostic models alongside clinicopathological characteristics. The validated prognostic nomogram may support personalized risk stratification and individualized dose-adjusted chemotherapy.