Systemic Inflammatory Biomarkers as Prognostic Indicators in Metastatic Colorectal Cancer: A Retrospective Study

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Abstract
Background and Objectives: Systemic inflammatory biomarkers have emerged as potential prognostic indicators in metastatic colorectal cancer (mCRC). However, the prognostic robustness of inflammatory indices such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), C-reactive protein (CRP), C-reactive protein-to-albumin ratio (CAR), and Glasgow Prognostic Score (GPS) remains incompletely characterized. In this study, we aimed to evaluate the prognostic significance of NLR, PLR, CRP, CAR, and GPS for progression-free survival in metastatic colorectal cancer in a cohort of patients from Romania. Materials and Methods: This retrospective observational study included 148 patients diagnosed with mCRC. Inflammatory biomarkers were determined from baseline laboratory parameters. Progression-free survival (PFS) was the primary endpoint. Statistical analyses included correlation testing, Kaplan–Meier survival analysis, Cox proportional hazards regression, Firth penalized Cox regression, restricted cubic spline modeling, time-dependent receiver operating characteristic (ROC) analysis, LASSO penalized regression, multiple imputation, and parsimonious multivariable Cox models adjusted for major clinicopathologic confounders. Results: Median PFS was 21 months (95% CI 19–24). In univariable Cox analyses, elevated NLR (HR 1.98, 95% CI 1.11–3.51, p = 0.020), PLR (HR 1.89, 95% CI 1.25–2.85, p = 0.002), CRP (HR 1.45, 95% CI 1.15–1.83, p = 0.002), and CAR (HR 1.44, 95% CI 1.05–1.98, p = 0.022) were associated with shorter PFS. Restricted cubic spline analysis demonstrated a significant nonlinear association between NLR and PFS (p = 0.0025). After multiple imputation, NLR remained associated with shorter PFS (HR 2.04, 95% CI 1.13–3.68, p = 0.018). However, in a multivariable model adjusted for major clinicopathologic confounders, this association was not retained (HR 1.41, 95% CI 0.81–2.43, p = 0.221) and time-dependent ROC analyses demonstrated its limited discriminatory performance. Conclusions: Although some inflammatory markers were associated with shorter PFS in univariable analyses, the prognostic effect of NLR was attenuated after adjustment and was not consistently confirmed across all analyses.

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