CEA and CA-19-9 Dynamics Associate with Survival in Regorafenib-Treated Metastatic Colorectal Cancer: A Real-World...

Background: Regorafenib is a standard late-line treatment for refractory metastatic colorectal cancer (mCRC), yet clinical outcomes remain heterogeneous. Identifying accessible biomarkers to predict therapeutic benefit is crucial for balancing efficacy and toxicity. This study evaluated the prognostic value of early dynamic changes in carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA-19-9). Methods: We conducted a retrospective real-world analysis of 61 heavily pretreated mCRC patients receiving regorafenib. Tumor markers were assessed at baseline and after the third cycle (approximately 12 weeks). Systematic threshold optimization using Cox proportional hazards regression and Akaike Information Criterion (AIC) was performed to identify optimal percentage change cutpoints for predicting survival. Results: The optimal thresholds for defining unfavorable marker increases were +14.6% for CEA and +23.5% for CA-19-9. Patients with CEA changes below the cutoff demonstrated significantly superior progression-free survival (PFS) (median 6.1 vs. 4.0 months, p = 0.012) and overall survival (OS) (11.05 vs. 6.0 months, p = 0.035). CA-19-9 changes below the cutoff were associated with improved PFS (p = 0.022) but did not reach statistical significance for OS (p = 0.23). In multivariable analysis, neither marker retained independent significance, likely due to collinearity. Conclusions: Early dynamics of routine tumor markers are prognostic in regorafenib-treated mCRC. specifically, a CEA increase of <14.6% significantly predicts improved survival outcomes. These findings support the utility of serial marker monitoring in real-world practice, though prospective validation is warranted.