Comparative prognostic value of preoperative SII, NLR, and MLR and their association with TNM staging in gallbladder
Zhenhao Huang1, Jing Luo1, Jintong He1
1Department of Hepatopancreatobiliary Surgery, Bishan Hospital of Chongqing Medical University, Chongqing, 402760, China.
Background:
Gallbladder cancer (GBC) has poor prognosis, and reliable preoperative biomarkers remain limited. Systemic inflammation-based indices, including systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), and monocyte-to-lymphocyte ratio (MLR), may predict outcomes, but their comparative value and association with TNM stage are unclear.
Methods:
This multicenter retrospective study included 210 patients who underwent curative-intent resection for GBC (2015-2023). Preoperative SII, NLR, and MLR were calculated from peripheral blood counts. Prognostic performance was evaluated by time-dependent ROC, Kaplan-Meier, and Cox regression analyses. Restricted cubic spline models assessed non-linear associations. Associations with TNM stage were analyzed using the Jonckheere-Terpstra trend test, and stratified survival analysis was conducted.
Results:
SII showed the highest predictive accuracy for overall survival (OS, AUC = 0.745) and recurrence-free survival (RFS, AUC = 0.689), outperforming NLR and MLR. In multivariable analysis, only elevated SII independently predicted poorer OS (HR = 4.601, 95% CI: 1.178-17.965, P = 0.028). Restricted cubic spline revealed an "S-shaped" non-linear relationship between SII and OS risk and a linear association with RFS. SII levels significantly increased with advancing TNM stage (P = 0.042) and provided superior prognostic stratification in advanced disease, while NLR and MLR showed weaker stage-related trends.
Conclusions:
Among SII, NLR, and MLR, preoperative SII showed comparatively stronger and more consistent associations within this retrospective multicenter cohort. SII independently predicted OS, correlated with TNM stage, and appeared to offer better stratification in advanced disease. As a simple and readily available biomarker, SII may be considered to complement TNM staging for preoperative risk assessment; however, these findings should be interpreted cautiously and require confirmation in prospective multicenter studies.
