Inflammation has a critical role in the development and progression of cancers. We developed a novel systemic inflammation score (SIS) based on lymphocyte, monocyte, and CA19-9 and explored its prognostic value in intrahepatic cholangiocarcinoma (ICC). From January 2005 to December 2011, 322 consecutive ICC patients who underwent curative resection in our center were included in this study, and validated in a retrospective study of 126 patients enrolled from 2012 to 2014. Clinicopathological variables including preoperative serum CA19-9 and LMR were analyzed. The cutoff values of CA19-9 and LMR were determined based on receiver operating characteristics curve analysis in the primary cohort. Kaplan-Meier curves and multivariate Cox-regression analyses were calculated for time to recurrence (TTR) and overall survival (OS). In univariate analysis of all patients, all three inflammatory and tumor marker including NLR ≥ 2.49 (P<0.001), LMR ≤ 4.45 (P=0.002), and CA19-9≥89 (P<0.001) were associated with poor prognoses. When omitting SIS in multivariate analysis, preoperative LMR (P =0.006) and serum CA19-9 (P<0.001) were independent predictors of OS. In addition, elevated CA19-9 (P=0.001), multiple tumors (P<0.001), and lymph node metastasis (P<0.001) were significant predictors of worse recurrence free survival. Moreover, high SIS was significantly associated with aggressive tumor behaviours including large tumor size (P<0.001), multiple tumors (P=0.033), lymphonodus node metastasis (P=0.001), and high TNM stage (P<0.0001). Finally, univariate and multivariate analyses revealed the SIS was an independent predictor for TTR (HR=2.077, 95% CI, 1.365-3.162, P=0.001) and OS (HR=3.133 95% CI, 2.058-4.769, P<0.001). These results were further confirmed in the validation cohort. In conclusions, our findings demonstrate that the SIS as a potentially powerful prognostic biomarker in ICC that predicts poor clinical outcomes and is a promising tool for ICC treatment strategy decisions.

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