Pretreatment Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio as Prognostic Factors and Reference Markers of Treatment Options for Locally Advanced Squamous Cell Carcinoma Located in the Middle and Upper Esophagus

Abstract

Background: Various inflammatory biomarkers, such as the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), have been well authenticated to predict clinical outcomes in numerous types of cancer. The optimal treatment for patients with locally advanced esophageal squamous cell carcinoma (ESCC) located in the middle or upper region is still inconclusive. The aim of the study was to examine pretreatment NLR and PLR to select from radical surgery or definitive chemoradiotherapy (dCRT) for these patients. The linkage between pretreatment NLR/PLR and prognosis was also analyzed.

Methods: NLR and PLR were calculated in 113 locally advanced ESCC located in the middle or upper esophagus of patients who underwent radical surgery or dCRT between January 2014 and December 2019. A receiver operating characteristic curve was plotted to select the best cut-off value of NLR and PLR for predicting survival. A survival curve was plotted using the Kaplan-Meier method. Univariate and multivariate Cox regression analyses were applied to assess predictors for survival.

Results: NLR and PLR were associated with the extent of lymph node metastasis (NLR: P = 0.045; PLR: P = 0.002). Additionally, high PLR and recurrence with distant organ metastasis were closely related (P = 0.014), and NLR was related to the tumor stage (P = 0.043). The results of the multivariate analysis revealed that NLR (>2.07) and PLR (>183.06) were independently associated with poor prognosis. It is noteworthy that surgery was associated with a superior OS compared with dCRT in the low NLR population (P = 0.045).

Conclusion: Low pretreatment NLR patients are fit to undergo radical surgery with a substantial therapeutic benefit. Pretreatment NLR and PLR are independent predictors for patients with locally advanced ESCC located in the middle and upper esophagus who underwent radical surgery or dCRT.

Keywords: definitive chemoradiotherapy; esophageal squamous cell carcinoma; neutrophil-to-lymphocyte ratio; platelet-to-lymphocyte ratio; prognostic factor; reference marker; surgery.

Figure 1

Association of therapeutic modalities of surgery versus definitive chemoradiotherapy (dCRT) with overall survival (A, P = 0.567) and progression-free survival (B, P = 0.642) in the overall population.

Figure 2

Receiver operating curves for overall survival were plotted to determine the optimum cut-off for NLR (A), PLR (B).

Figure 3

Association of NLR (> 2.07 versus ≤ 2.07) or PLR (> 183.06 versus ≤ 183.06) with overall survival (A, P = 0.000 and B, P = 0.000).

Figure 4

Association of therapeutic modalities of surgery versus definitive chemoradiotherapy (dCRT) with overall survival in high NLR population (A, P = 0.768), high PLR population (B, P = 0.678), low PLR population (C, P = 0.451) and low NLR population (D, P = 0.045).