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

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.