The Lymphocyte-to-Monocyte Ratio is a Superior Predictor of Overall Survival in Comparison to Established Biomarkers of Resectable Colorectal Cancer

Abstract

Objective: The study aims to investigate the prognostic value of the lymphocyte-to-monocyte ratio (LMR) in patients with colorectal cancer (CRC) undergoing curative resection and to compare it to established biomarkers including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), modified Glasgow prognostic score (mGPS), and combined BRAF-mismatch repair (MMR) status.

Background: The prognostic significance of systemic inflammatory markers in CRC such as the NLR, PLR, and mGPS has been well defined. Commonly used genetic markers such as combined BRAF-MMR status have also been found to be prognostic. Recent evidence, although limited, suggests that the preoperative LMR may be prognostic in CRC.

Methods: Data from the Northern Sydney Local Health District from January 1998 to December 2012 were retrospectively collected. Of 3281 consecutive patients identified, 1623 patients who underwent curative resection were deemed eligible for inclusion. The relation between the LMR, clinicopathologic variables, and other biomarkers were analyzed in Kaplan-Meier log-rank survival analysis and then multivariate Cox regression models looking for association with overall survival (OS).

Results: In multivariate analysis of all patients, elevated LMR was associated with better OS (hazard ratio 0.569, 95% confidence interval: 0.478-0.677, P < 0.001) independent of age (P < 0.001), T stage (P < 0.001), N stage (P < 0.001), and grade (P = 0.049). The NLR, PLR, and combined BRAF-MMR status were not independently significant. In multivariate subgroup analysis of 389 patients with mGPS, LMR remained the only independently significant biomarker (hazard ratio 0.620, 95% confidence interval: 0.437-0.880, P = 0.007).

Conclusions: The LMR is an independent predictor of OS in patients with CRC undergoing curative resection and appears to be superior to pre-existing biomarkers.

FIGURE 1

Flow chart of the patient cohort based on inclusion and exclusion criteria.

FIGURE 2

Hazard ratios for overall survival according to subgroups (age, sex, stage, and site). Hazard ratios were derived from a Cox proportional hazards model.

FIGURE 3

Relation between OS and LMR by stage. Top left: relation between OS and stage 1 CRC (P < 0.001). Top right: relation between OS and stage 2 CRC (P < 0.001). Bottom left: relation between OS and stage 3 CRC (P < 0.001). Bottom right: relation between OS and pooled stage 1 to stage 3 patients with CRC (P < 0.001).

FIGURE 4

Overview of the interactions of the tumor microenvironment. Cytokines, growth factors, proteases, and other mediators are secreted both in the tumor and into systemic circulation where they exert local and systemic inflammatory effects. One particular effect is changes to the hematologic system. The LMR therefore reflect inflammatory processes not only at the tumor level but also systemically.