A Multicenter Study of Systemic Inflammatory Biomarkers for Prognostic Evaluation in iCCA Patients

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.

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.

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.

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.