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Re: Ratios derived from an array of standard haematological indices predict the oncological outcome in colon cancer

Dear Editor, We read with interest the article by East, Hogan and colleagues highlighting the negative impact of a preoperative neutrophil lymphocyte (NLR) count >3.4 and white-cell lymphocyte (WLR) count >5.28 on oncological outcomes following colon cancer [1]. Those authors are the first to report the use of a classification and regression tree analysis in providing specific values of the haematological indices predictive of survival in patients with all stages of colon cancer. The authors are acknowledged for their effort to add to the growing evidence linking the impact of the systematic inflammatory response to tumour on the outcome following surgical resection and prognosis in various gastrointestinal cancers [2–4]. They used a training dataset in 436 patients undergoing surgical resection with curative intent for all stages of colon cancer to identify the prognostic values of NLR > 3.4 and WLR > 5.28 and applied them to a test set of 50 patients. Mean overall survival (OS) was decreased by 4 and 7 months, respectively, in those with elevated NLR and WLR and the pattern was confirmed in relation to disease-free survival (DFS). We wish to focus our comment on the study design. While the statistical analysis and interpretation of the data are robust, there are some confounding variables that need to be considered if the results relating NLR and WLR to survival are to be accepted. The authors did not report the percentage of patients with Stage 4 disease in the training set, but in the test set (which is assumed to be representative) this was up to 15% (7/50). This proportion of patients by definition therefore had distant and systemic biological disease at the beginning of the analysis. We suggest that the inclusion of patients with Stage 4 disease has the potential for bias because the tumour biology and systemic host environment are quite different from the situation in Stage 1–3 disease. Indeed, with regard to the NLR, of the seven patients with Stage 4 disease in the test dataset, 5/ 7 (70%) had NLR > 3.4 and up to three times as many patients had distant disease in the WLR > 5.28 group. Thus we propose that an analysis of NLR and WLR on OS and DFS excluding patients with Stage 4 disease could provide more meaningful information and determine for which group of patients it might best influence the selection of treatment. Furthermore it is possible that some patients with an elevated preoperative white cell/ neutrophil count could have displayed features of infection from various sources, adding to potential bias. In light of the increasing number of reports indicating the negative impact of preoperative NLR (and WLR) on long-term outcome, an analysis of the longitudinal pattern of indices after resection, and in particular at the time of the detection of recurrence, is now much needed. Specifically, do values of NLR > 3.4 and WLR > 5.28 fall after surgical resection of tumour and do they precede recurrence? The authors are encouraged to pursue this aspect if the data are readily available, providing yet further evidence linking NLR/WLR and cancer and the potential benefits of a cheap and accessible biomarker in clinical practice.