Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio as Prognostic Factors in Locally Advanced Rectal Cancer

Abstract

INTRODUCTION The standard therapy for locally advanced rectal cancer is based on neoadjuvant chemoradiotherapy (nCRT) with fluoropyrimidines. There are different biomarkers used as prognostic factors in these tumors. Some studies advocate the use of the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) as prognostic factors in this clinical scenario. The aim of the study is to evaluate NLR and PLR as prognostic factors of disease-free survival (DFS) and overall survival (OS) and as predictive factors of pathological complete response (pCR) using Ryan tumor regression scoring system on surgical specimens, in patients with locally advanced rectal adenocarcinoma who received nCRT and radical surgery. METHODS We retrospectively evaluated patients with locally advanced rectal adenocarcinoma (T3-T4, N1-N3, M0 according to the TNM classification, AJCC 8th edition) who received neoadjuvant chemoradiotherapy based on fluoropyrimidines and radical surgery. Complete blood cell count before nCRT were obtained to calculate NLR and PLR. We made subgroups of patients according to NLR and PLR. We obtained the cut-off point for these ratios based on receiver operating characteristic analysis. We analyzed OS and DFS using the Kaplan-Meier method and Cox proportional hazard models. The relationships between NLR/PLR and pCR, along with other clinical-pathological characteristics were evaluated by Pearson´s χ2 or Fisher´s exact test as appropriate. Multivariate analyses were performed using Cox proportional hazard regression models. RESULTS Between February 2012 and February 2017, 100 consecutive patients were treated according to the reported schedules. Median age was 76 years (68-83). All patients received radiotherapy up to 50,4 Gy and 5-FU-based chemotherapy. 100% completed nCRT and surgery. 38% had elevated basal NLR (cut-off >1,95), 50% had elevated basal PLR (cut-off >133). After a median follow-up of 72 months (55-88), a lower DFS was obtained in the high NLR subgroup (Long Rank, Mantel-Cox 5,165, p=0,023) and in the high PLR subgroup (Long Rank, Mantel-Cox 13,971, p=0,001). Multivariate analysis showed that PLR (p=0,006) was a strong significant predictor of DFS. A lower overall survival was observed in the high NLR and PLR subgroup without significant differences (Long Rank, Mantel-Cox 1,245, p= 0,265; 0,578, p=0,447). No significant differences were obtained in any of the subgroups analysis regarding pCR rates. CONCLUSION In light of our results, both NLR and PLR could be considered prognostic factors for DFS in patients with LARC that receive treatment with nCRT followed by surgery.