Abstract
BACKGROUND: The prognostic value of systemic inflammatory biomarkers in intrahepatic cholangiocarcinoma (iCCA) remains uncertain. This study aimed to compare their predictive performance and identify the most effective indicator. METHODS: We retrospectively analyzed 312 iCCA patients who underwent curative resection at three medical centers (2014-2022). Twelve systemic inflammatory biomarkers, derived from routine blood parameters (neutrophils, lymphocytes, monocytes, platelets, albumin), were assessed for overall survival (OS) and disease-free survival (DFS). Prognostic accuracy was evaluated using the concordance index (C-index), time-dependent area under the ROC curve (time-AUC), and Brier score. Independent predictors identified by multivariate Cox regression were incorporated into nomograms to estimate survival. RESULTS: The median patient age was 63 years, 71.8% were male, 38.8% had stage III disease, and 37.5% had poorly differentiated tumors. Median follow-up was 24 months. Among the twelve biomarkers, the pan-immune-inflammation value (PIV) demonstrated the strongest prognostic performance. For OS, PIV achieved a C-index of 0.682, time-AUC of 0.695, and Brier score of 0.180; for DFS, C-index was 0.679, time-AUC 0.681, and Brier score 0.192. Unlike single-ratio indices, PIV integrates neutrophil, monocyte, platelet, and lymphocyte counts, providing a multidimensional view of systemic inflammation and immunity. Multivariate analysis confirmed high PIV as an independent predictor of poor OS (HR = 2.488; 95% CI: 1.745-3.546; P < 0.001) and DFS (HR = 2.353; 95% CI: 1.701-3.247; P < 0.001). Nomograms combining PIV with clinicopathological factors (CEA, CA19-9, perineural invasion, TNM stage) demonstrated improved discrimination and calibration at 12, 36, and 60 months. CONCLUSION: PIV provides superior prognostic value compared with traditional inflammatory indices, offering a cost-effective and readily available biomarker for iCCA. While promising, these results are based on a retrospective multicenter cohort without independent validation, and should be confirmed in prospective external studies.