Prognostic value of platelet-to-lymphocyte ratio in oncologic outcomes of esophageal cancer: what should we expect from a meta-analysis?

Dear Editor,

We read with interest the work by Zhang et al. ¹ published in the April 2018 issue of the International Journal of Biological Markers. These authors performed a meta-analysis to evaluate the association between the platelet-to-lymphocyte ratio (PLR) and the oncologic outcome of esophageal cancer patients. Nineteen articles with 6134 patients from 2011 to 2017 were included in their meta-analysis. The authors demonstrated that high PLR is associated with poor overall survival in patients with esophageal cancer. This is an interesting systematic review and meta-analysis in our understanding concerning the establishment of a biomarker with significant prognostic ability for this type of cancer. However, before the results of this meta-analysis achieve wider uptake, a few points should be taken into account. It is well known that in a meta-analysis the interpretation of the results of included studies is analyzed by advanced mathematical models in order to precisely calculate a common pooled effect. As a result, the conclusions of a meta-analysis are directly proportional to the quality of the included studies. ² This meta-analysis included studies with different designs, making the conclusions controversial.

There is significant heterogeneity in the studies that the authors decided to include in their meta-analysis: mainly the histological type of the esophageal cancer (squamous cell carcinoma or adenocarcinoma), the treatment methods (surgery, chemotherapy, or chemo-radiotherapy), the cut-off value of PLR (the cut-off point ranged from 103 to 300), the definition of outcomes after treatment (cancer-specific survival, disease-free survival, disease-specific survival, progression-free survival), the stage of disease, the neoadjuvant and/or adjuvant treatment, the timing of intervention, and the demographic differences.

Also we noticed significant heterogeneity among the included studies for categorized PLR (I²=72.20%; P < 0.001) as well as the relationship between ethnicity and PLT (I²=83.90%; P=0.013); the association between cut-off value and PLT (I²=65.60%; P=0.008); and the correlation between treatment strategies and PLT (I²=72.20%; P=0). The above important heterogeneity significantly reduces the statistical power because the included studies have widely varying outcomes.^3,4

Additionally, the vast majority of the research studies took place in Asian countries apart from three, which were performed in the UK. For this reason, these preliminary results have to be proven and compared with other regions. Furthermore, squamous cell carcinoma (SCC) was the predominant histological subtype. It is well known that SCC compared with the adenocarcinoma and the small-cell carcinoma of the esophagus has a different prognosis and cell biological behaviors. Further studies are needed in order to compare the different geographic regions and the histological subtypes of esophageal cancer.