Preoperative prediction of microvascular invasion in Intra-hepatic cholangiocarcinoma using serum tumor markers integrated with inflammatory and liver function indices
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.
Authors
- Haizhou Qiu (ORCID: https://orcid.org/0000-0001-9421-0874)
- Yiwen Qiu (ORCID: https://orcid.org/0000-0003-0022-4824)
- Jiang Li (ORCID: https://orcid.org/0000-0002-5539-8760)
- Wentao Wang (ORCID: https://orcid.org/0009-0000-6439-5329)
- Kunlin Chen (ORCID: https://orcid.org/0000-0002-0673-8001)
- Yi Yang (ORCID: https://orcid.org/0009-0009-7760-333X)
- Tao Wang (ORCID: https://orcid.org/0000-0003-4140-8734)
Institutions
- Sichuan University (CN)
- West China Hospital of Sichuan University (CN)
Publication Details
- Journal
- BMC Cancer
- Published
- 2025-12-02
- DOI
- https://doi.org/10.1186/s12885-025-15245-y
- Primary Topic
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Type
- article
- Field-Weighted Citation Impact
- 0.00