Neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios as predictive and prognostic markers in patients with locally advanced rectal cancer treated with neoadjuvant chemoradiation

Abstract

Background A standard therapy for locally advanced rectal cancer (LARC) includes fluoropyrimidine (FP)-based neoadjuvant chemoradiation (nCRT). Previous studies have inconsistently demonstrated that baseline neutrophil- and platelet-to-lymphocyte ratios (NLR and PLR) are predictive of response to nCRT or prognostic of outcomes in LARC. Methods We reviewed patients with LARC undergoing nCRT followed by surgery from 2005 to 2013 across 8 Canadian cancer centres. Outcome measures of interest were pathological complete response (pCR), disease-free survival (DFS) and overall survival (OS). Logistic regression and Cox proportional hazard models were used to assess for associations between baseline hematologic variables and outcomes. Results Of 1527 identified patients, 1237 (81%) were included in the DFS/OS analysis. Median age was 62 (range 23–88), 69% were male, and 80% had performance status (PS) 0–1. Twenty-six percent had elevated NLR (≥ 4), and 66% had elevated PLR (≥ 150). Ninety-seven percent of patients received FP-based nCRT, with 96% receiving ≥44 Gy. 81% completed neoadjuvant chemotherapy and 95% completed neoadjuvant radiotherapy, with a pCR rate of 18%. After a median follow-up time of 71 months, 8% developed local recurrence, 22% developed distant recurrence and 24% died. 5-year DFS and OS were 69% (95% CI 66–72%) and 79% (95% CI 77–82%), respectively. In multivariate analyses, elevated baseline NLR and PLR were neither prognostic for DFS and OS nor predictive of pCR. Conclusions NLR and PLR were not found to be independently prognostic for DFS or OS and did not predict for pCR in patients with LARC undergoing nCRT followed by surgery.

Pretreatment Albumin-to-Fibrinogen Ratio Independently Predicts Chemotherapy Response and Prognosis in Patients with Locally Advanced Rectal Cancer Undergoing Total Mesorectal Excision After Neoadjuvant Chemoradiotherapy

“… 34 A clinical trial by Dudani et al reported that NLR and platelet-to-lymphocyte ratio (PLR) are two useful predictive and prognostic markers in LARC patients. 35 However, some other studies did not indicate a significant association between NLR, PLR and outcomes in LARC patients. 36 , 37 A recent meta-analysis by Jin et al indicated lymph node ratio (LNR) as an independent prognostic factor for RC patients after nCRT.…”

Meta-Analysis on the Neutrophil-Lymphocyte Ratio in Rectal Cancer Treated With Preoperative Chemoradiotherapy: Prognostic Value of Pre- and Post-Chemoradiotherapy Neutrophil-Lymphocyte Ratio

“…Our study included only patients receiving preoperative CRT before surgery, and pre-CRT NLR significantly correlated with survival. Meanwhile, a Canadian multicenter study (28) with the largest effect size reported that an elevated pre-CRT NLR level is not associated with OS on both univariate and multivariate analyses. When the patient and tumor characteristics were compared according to the pre-CRT NLR level, a higher pre-CRT NLR was associated with older age, poor performance status, and lower hemoglobin level, of which age and performance status were significant prognostic factors affecting OS on multivariate analysis.…”

Pretreatment Inflammatory-Nutritional Biomarkers Predict Responses to Neoadjuvant Chemoradiotherapy and Survival in Locally Advanced Rectal Cancer

“…Of note, this study differed from previous studies in methodology. A common feature of previous studies was to dichotomize continuous biomarkers primitively to stratify patients into different subgroups to explore the correlations of these biomarkers with response or prognosis, and thus the cut off values of these biomarkers are various in different literature (17,(24)(25)(26)(27)(28)(31)(32)(33)(34)(35). In this study, we choose not to dichotomize these biomarkers primitively, because the forecasts of continuous variables have enormous advantages from a statistical standpoint.…”

“…Kim et al reported that NLR, LMR, and PLR could not be used to distinguish total tumor regression from the residual disease after nCRT; while higher PLR was correlated with improved recurrence-free survival ( 31 ). Michael et al found that NLR and PLR are neither independent predictors of response nor prognostic factors in LARC patients undergoing nCRT followed by radical surgery ( 32 ). However, the data from William et al showed that baseline lower levels of LMR and higher levels of NLR and PLR were correlated with decreased OS ( 25 ).…”