Abstract: ObjectiveTo investigate the prognostic values of systemic inflammatory markers, including preoperative neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and the lymphocyte-to-monocyte ratio (LMR), in patients with esophageal squamous cell carcinoma (ESCC) by curative esophagectomy. Methods  A total of 117 patients with ESCC from January 2010 to December 2012 in Affiliated Taixing People′s Hospital of Yangzhou University were retrospectively analyzed. They were treated with standard curative esophagectomy. These patients were divided into NLR≥2.8 group and NLR＜2.8 group, PLR≥127.3 group and PLR＜127.3 group, LMR≥3.8 group and LMR＜3.8 group for comparing the patients′ general survival conditions and analyzing the influence on the progression-free survival (PFS) and overall survival (OS) rates  according to the median values 2.8, 127.3, 3.8 of NLR, PLR and LMR, respectively. The COX proportional hazards models of NLR, PLR and LMR were used to carry out univariate and multivariate analyses for PFS and OS. The evaluation of prognostic values of NLR, PLR and LMR were carried by receiver operating characteristic (ROC) curve. Results  For 117 patients, the median PFS time was 17 months, and the PFS rates at the 1-, 3- and 5-year period were 66.7%, 21.4% and 17.9%, respectively; the median OS time was 36 months, and the OS rates at the 1-, 3- and 5-year time were 94.9%, 46.2% and 28.2%, separately. In addition, a close relationship was identified between high NLR, high PLR, low LMR and tumor relapse (all P<0.05). Furthermore, in the NLR<2.8 group, the median PFS time was 24 months (95%CI: 19.788-28.212),  and the 1-, 3-, 5-year PFS rates were 78.9%, 35.1% and 31.6% separately, while in the NLR≥2.8 group, the median PFS time was 13 months (95%CI: 10.153-15.847), and the 1-, 3-, 5-year PFS rates were 55.0%, 8.3% and 5.0%, respectively (χ²=15.601, P<0.001). In the PLR<127.3 group, the median PFS time was 24 months (95%CI: 19.891-28.109), and the 1-, 3-, 5-year PFS rates were 78.0%, 30.5% and 27.1%. In the PLR≥127.3 group, the median PFS time was 15 months (95%CI: 11.832-18.168), and the 1-, 3-, 5-year PFS rates were 55.2%, 12.1% and 8.6% (χ²=7.621, P=0.006). In the LMR<3.8 group, the median PFS time was 14 months (95%CI: 11.534-16.466), and the 1-, 3-, 5-year PFS rates were 57.9%, 8.8% and 5.3%, while in the LMR≥3.8 group, the median PFS time was 21 months (95%CI: 16.783-25.217), and the 1-, 3-, 5-year PFS rates were 75.0%, 33.3% and 30.0% (χ²=10.201, P=0.001). Correspondingly, the median OS time was 42 months (95%CI: 29.188-48.282) and the 1-, 3-, 5-year OS rates were 98.2%, 56.1% and 47.4% in the NLR<2.8 group. While the median OS time was 27 months (95%CI: 20.358-33.642) and the 1-, 3-, 5-year OS rates were 91.7%, 36.7% and 10.0% in the NLR≥2.8 group (χ²=19.161, P<0.001). The median OS time was 38 months (95%CI: 31.31044.690) and the 1-, 3-, 5-year OS rates were 94.9%, 54.2% and 37.3% in the PLR<127.3 group and the median OS time was 27 months (95%CI: 19.537-34.463) and the 1-, 3-, 5-year OS rates were 93.1%, 37.9% and 19.6% in the PLR≥127.3 group (χ²=7.019, P=0.008). The median OS time was 30 months (95%CI: 23.659-36.341) and the 1-, 3-, 5-year OS rates were 91.2%, 36.8% and 12.3% in the LMR<3.8 group. While the median OS time was 38 months (95%CI: 27.878-48.121) and the 1-, 3-, 5-year OS rates were 95.0%, 55.3% and 43.3% in the LMR≥3.8 group (χ²=10.201, P=0.001). In univariate analysis, the following factors were significantly associated with poor PFS: T stage (HR=1.292, 95%CI: 1.077-2.211, P=0.048), N stage(HR=1.773, 95%CI: 1.186-2.651, P=0.005), TNM stage (HR=1.768, 95%CI: 1.181-2.645, P=0.006), NLR (HR=2.193, 95%CI: 1.450-3.316, P＜0.001), PLR(HR=1.722, 95%CI: 1.149-2.581, P=0.009) and LMR (HR=0.531, 95%CI: 0.353-0.799, P=0.002). The univariate analysis further revealed that T stage (HR=1.982, 95%CI: 1.162-3.383, P=0.012), N stage (HR=1.910, 95%CI: 1.243-2.934, P=0.003）, TNM stage (HR=2.115, 95%CI: 1.375-3.252, P=0.001), NLR (HR=2.599, 95%CI: 1.657-4.078, P＜0.001), PLR (HR=1.764, 95%CI: 1.145-2.717, P=0.010) and LMR (HR=0.470, 95%CI: 0.3030.728, P=0.001) were also significantly associated with poor OS. Furthermore, multivariate COX regression analysis showed that TNM stage (HR=1.608, 95%CI: 1.057-2.445, P=0.026) and NLR (HR=1.886, 95%CI: 1.133-3.138, P=0.015) were independent prognostic factors for PFS in patients with ESCC after surgery. Correspondingly, TNM stage (HR=1.867, 95%CI: 1.190-2.928, P=0.007) and NLR （HR=2.226, 95%CI: 1.292-3.835, P=0.004) were also independent prognostic factors for OS in ESCC patients following surgery. Finally, ROC curves of NLR, PLR and LMR for PFS predictive values were as follows: the area under the curve (AUC) for NLR, PLR and LMR were 0.725 (95%CI: 0.615-0.835, P=0.001), 0.657 (95%CI: 0.533-0.781, P=0.025) and 0.290 (95%CI: 0.178-0.402, P=0.003), respectively. ROC curve analysis of NLR, PLR and LMR in diagnostic value of OS indicated that the AUC was 0.731 (95%CI: 0.632-0.829, P＜0.001) for NLR, 0.613 (95%CI: 0.501-0.726, P=0.057) for PLR and 0.308 (95%CI: 0.205-0.412, P=0.053) for LMR. Conclusion  NLR is superior to PLR and LMR in predicting the survival outcome of patients with ESCC, and NLR is of great value in predicting the survival and prognosis of patients with thoracic ESCC after operation.

Key words: Esophageal neoplasm, Prognosis, Blood inflammatory markers