Preoperative prediction of microvascular invasion in Intra-hepatic cholangiocarcinoma using serum tumor markers integrated with inflammatory and liver function indices

TL;DR

This study creates a blood test model to predict microvascular invasion in intra-hepatic cholangiocarcinoma before surgery, which could help guide treatment decisions.

Contribution

A novel blood-based model integrating tumor markers, inflammation, and liver function indices for preoperative prediction of microvascular invasion in ICC.

Findings

The model achieved an optimism-corrected AUC of 0.78, outperforming tumor-marker-only models.

High-risk patients showed significantly higher early recurrence and lower survival rates.

The model provided consistent net benefit across clinically relevant risk thresholds.

Abstract

Microvascular invasion (MVI) critically portends early recurrence and poor survival in intra-hepatic cholangiocarcinoma (ICC) but is ascertainable only after resection. An accurate pre-operative predictor of MVI would aid surgical planning in everyday practice.

To develop and internally validate a blood-based model that integrates serum tumor markers with inflammatory and liver-function indices for pre-operative estimation of MVI in ICC.

This single-center, retrospective, non-interventional cohort included consecutive adults who underwent curative-intent hepatectomy for pathologically proven ICC and completed 3-year follow-up between January 2019 and December 2024. Of 602 patients screened, 450 met eligibility criteria after excluding cases with mixed histology, neoadjuvant therapy, macro-vascular invasion, or missing key data. Pre-operative variables (drawn ≤ 14 days before surgery) comprised CA19-9, CEA, AFP, CA-125, neutrophil-to-lymphocyte ratio (NLR), γ-glutamyl-transferase (γ-GT), albumin, maximum tumor diameter, and lesion multiplicity. Predictors were selected by LASSO, and a shrinkage-adjusted logistic model was internally validated with 1,000-bootstrap resamples. Performance was benchmarked against a tumor-marker-only model and evaluated for clinical utility using decision-curve analysis (DCA). Associations between model-predicted risk, early recurrence (≤ 12 months), and overall survival were explored with Cox regression.

Among 450 eligible patients (median age 58 y; 64.2% male), microvascular invasion (MVI) was present in 40.4% (182/450). The final model retained log‑transformed CA 19‑9, CEA, NLR and γ‑GT together with albumin, tumor size and lesion multiplicity. Its apparent and optimism‑corrected AUCs were 0.80 (95% CI 0.76–0.84) and 0.78, respectively—outperforming the tumor‑marker baseline (corrected AUC 0.68; ΔAUC + 0.10). Across clinically relevant thresholds of 12.0–38.0% the extended model delivered consistently higher net benefit than both the baseline and “treat‑all” strategies. Patients assigned to the high‑risk tier (> 29.5% predicted probability; n = 169) showed markedly higher early‑recurrence rates (52.8% vs. 18.6%; adjusted HR 2.9, 95% CI 2.1–4.0) and lower three‑year overall survival (44.3% vs. 72.1%; adjusted HR 2.1, 95% CI 1.5–3.0).

A composite model that integrates routine serum tumor markers with inflammatory and liver‑function indices shows strong internal discrimination for pre‑operative estimation of MVI in ICC. Because this is a single‑center, HBV-enriched Chinese cohort, generalizability to other settings and etiologies is uncertain. External, multicenter validation and site‑specific recalibration are warranted before clinical adoption.

The online version contains supplementary material available at 10.1186/s12885-025-15245-y.

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