Mehmet Cem Fidan, Murad Guliyev, Emir Çerme, Hamza Abbasov, Vali Aliyev, Berrin Papila, Nebi Serkan Demirci, Özkan Alan, Çiğdem Papila
Background: The C-reactive protein/albumin ratio (CAR) has emerged as a prognostic biomarker across several malignancies, but its role in de novo metastatic colorectal cancer (mCRC) has not been evaluated using a propensity score-matched design. Methods: This retrospective study included 212 patients with mCRC who received first-line fluoropyrimidine-based chemotherapy plus a biological agent. The optimal CAR cutoff (2.69) was determined by ROC analysis (AUC = 0.714). Propensity score matching (PSM), incorporating 16 clinical, pathological, and molecular covariates, was performed to balance low-CAR and high-CAR groups. Progression-free survival (PFS) and overall survival (OS) were compared using Kaplan-Meier and multivariate Cox regression analyses. Results: PSM yielded 65 matched pairs (130 patients), eliminating all baseline imbalances present in the unmatched cohort. In the matched cohort, high CAR remained associated with shorter PFS (median 8.4 vs. 12.9 months; HR = 1.58, 95% CI 1.10-2.30, p = 0.014) and OS (median 22.7 vs. 31.1 months; HR = 1.70, 95% CI 1.15-2.50, p = 0.006). On multivariate analysis, CAR retained independent significance for OS (HR = 1.792, 95% CI 1.157-2.775, p = 0.009) alongside CEA level (HR = 3.331, p < 0.001) and BRAF mutation status (HR = 4.543, p = 0.040), but not for PFS, where mucinous component (HR = 2.335, p = 0.015) and CEA level (HR = 2.231, p = 0.045) were the dominant independent predictors. Conclusions: Baseline CAR is an independent prognostic factor for OS in mCRC, even after adjusting for established clinicopathological and molecular risk factors through propensity score matching. As an inexpensive and readily available biomarker, CAR may help identify patients with more aggressive disease biology who warrant closer monitoring, although prospective validation is needed before clinical implementation.