Neutrophil-to-lymphocyte ratio as a biomarker for prognosis in localized colorectal carcinoma

Background

Adjuvant therapy in Stage II colorectal cancer is controversial. Recently a molecular classification has identified four main molecular subtypes (canonical, mesenchymal, metabolic and immune) with potential clinical implication (Guinney, 2015). Because neutrophil-to-lymphocyte ratio (NLR) has been described as a surrogate marker of the immune sub-type, we evaluate if NLR characterize a subgroup of patients (pts) with different prognosis.

Methods

The aim of this study was to develop a cutoff for NLR to predict relapse-free survival of CRC pts in a training-set and validate it in an independent cohort of pts. Receiver operating characteristic (ROC) curve was used to determine the optimal cutoff for NLR. Relapse-free survival (RFS) was estimated by the Kaplan-Meier method.

Results

The training set consist of 187 resected CRC pts of Hospital de la Fe de Valencia (HFV) and the validation set consist of 423 resected CRC pts of Hospital Clínic de Barcelona (HCB). At baseline, HFV pts were younger 65 years (25-85 years) vs 75 (50-94 years), with more advanced stage (stage III; 53% vs 41%) and treated more frequently with adjuvant therapy (58.3% vs 26.9%), than pts in the HCB cohort. The optimal cutoff in the training set was 2.2 (80.4% of sensitivity and a 99% of specificity). Accordingly to the cutoff, 77 pts (41.2%) have high NLR. Relapse-free survival was 17% in high NLR group vs 74% in the low NLR at 3 year follow up (FU) (p = 0.0001) with a Hazard ratio (HR) of 3.6 (95%CI 1.88-6.38) in the multivariate analysis. According to the previous cutoff, high NLR ratio was found in 309 (73%) out of 423 patients. RLF was 72.2% (95% IC 66.9-77.5) in high NLR and 88.3% (95 IC 81.8-94.8) in low NLR at 3-year FU (p = 0.01) with a HR of 1.9 (95% CI 1.05-3.3) in the multivariate analysis.

Conclusions

High NRL identify a group of resected patients more likely to relapse. NLR could be useful for stratification, especially with novel therapies (i.e. immunotherapy).

Clinical trial identification

Legal entity responsible for the study

Hospital Clinic de Barcelona

Funding

N/A

Disclosure

All authors have declared no conflicts of interest.