Prognostic Role of Pretreatment Neutrophil-to-lymphocyte Ratio in Non-Small Cell Lung Cancer Patients Treated With Systemic Therapy

A Meta-Analysis

Zimu Wang; Ping Zhan; Yanling Lv; Kaikai Shen; Yuqing Wei; Hongbing Liu; Yong Song


Transl Lung Cancer Res. 2019;8(3) 

In This Article

Abstract and Introduction


Background: Neutrophil-to-lymphocyte ratio (NLR) is related to prognosis in non-small cell lung cancer (NSCLC). However, no consensus on the relationship of pretreatment NLR and survival outcomes of systemic therapy in NSCLC exists. This meta-analysis investigated the prognostic role of pretreatment NLR during systemic therapy for NSCLC, including chemotherapy, immunotherapy and targeted therapy.

Methods: PubMed, Web of Science and Cochrane Library databases were systematically searched up to April 09, 2019. Hazard ratios (HRs) with their 95% confidence intervals (CIs) were pooled to investigate the association of pretreatment NLR with progression-free survival (PFS) and overall survival (OS).

Results: In total, 27 articles with 4,298 participants were selected. The pooled results showed that elevated pretreatment NLR was associated with inferior PFS (HR, 1.45, 95% CI, 1.28–1.66) and OS (HR, 1.63, 95% CI, 1.43–1.84) during systemic therapy. Subgroup analyses according to the treatment strategy suggested that higher pretreatment NLR was significantly associated with shorter survival in all therapies, including chemotherapy (PFS HR, 1.74, 95% CI, 1.39–2.17; OS HR, 1.73, 95% CI, 1.26–2.36), immunotherapy (PFS HR, 1.53, 95% CI, 1.27–1.84; OS HR, 2.50, 95% CI, 1.60–3.89) and targeted therapy (PFS HR, 1.53, 95% CI, 1.04–2.25; OS HR, 1.92, 95% CI, 1.14–3.24).

Conclusions: Pretreatment NLR is a promising prognostic indicator for NSCLC patients receiving systemic therapy, including chemotherapy, immunotherapy and targeted therapy.


Lung cancer is the most commonly diagnosed cancer and a leading cause of cancer death.[1] Surgical treatment can be curative, but efficacy is limited to early stage lung cancer.[2] The majority of patients are diagnosed with metastatic diseases at the initial visit, which highlights the importance of effective systemic therapies.[3] The traditional therapy is chemotherapy, and certain gene expression patterns[4,5] and liquid biomarkers[6,7] serve as predictors of chemotherapy outcomes. Targeted therapy with small molecule tyrosine kinase inhibitors and immunotherapy with immune checkpoint inhibitors has improved patient survival and transformed the treatment paradigm of non-small cell lung cancer (NSCLC). According to the National Comprehensive Cancer Network guideline of NSCLC (Version 3. 2019), targeted therapy is the standard front-line treatment for advanced NSCLC patients with driver mutations, and pembrolizumab is the preferred first-line treatment for programmed cell death protein 1 ligand (PD-L1) expressing advanced NSCLC patients harboring negative driver mutations. The identification of targetable gene alterations can help select patients who may benefit from targeted therapy, whilst PD-L1 expression[8,9] and the tumor mutational burden (TMB)[10–12] are proposed biomarkers for both the response and outcome of immunotherapy.

Neutrophil-to-lymphocyte ratios (NLR), defined as the absolute neutrophil count (ANC) divided by the absolute lymphocyte count (ALC) from whole blood, can be easily and inexpensively accessed from regular blood tests and are associated with the prognosis of various cancers,[13,14] including lung cancer.[15,16] Our previous study indicated that elevated pretreatment NLR is an independent predictor of inferior survival for NSCLC patients receiving chemotherapy,[17] which has been conflicted[18–20] and supported[21–24] by other studies. To our knowledge, no consensus on this relationship has been reached and there are a lack of recent meta-analyses (MAs) that comprehensively assess the relationship between pretreatment NLR and systemic treatment outcomes for NSCLC. We therefore performed an MA by referring to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement, to investigate the prognostic role of pretreatment NLR from whole blood during lung cancer systemic therapy, including chemotherapy, immunotherapy and targeted therapy.