Locoregional therapies for intrahepatic cholangiocarcinoma: a stage-stratified, biology-informed multidisciplinary framework-a narrative review.

BACKGROUND AND OBJECTIVE: Intrahepatic cholangiocarcinoma (iCCA) is an aggressive primary liver malignancy with rising global incidence; most patients present with unresectable disease, and intrahepatic recurrence is common after curative-intent surgery. Locoregional therapies (LRTs), including future liver remnant (FLR) augmentation, percutaneous ablation, transarterial chemoembolization (TACE), transarterial radioembolization (TARE), hepatic arterial infusion chemotherapy (HAIC), and stereotactic body radiotherapy (SBRT), are increasingly applied across the disease continuum. This narrative review focuses primarily on unresectable iCCA, while also addressing surgical-adjunct and downstaging roles, and aims to clarify how each modality is best integrated within modern multimodal management. METHODS: We performed a focused literature search of PubMed/MEDLINE for English-language publications from January 2000 through March 2026, combining population terms ("cholangiocarcinoma", "intrahepatic cholangiocarcinoma", "iCCA", "biliary tract cancer") with intervention terms covering the principal locoregional modalities. Supplementary targeted searches were performed for context on epidemiology, systemic and targeted therapy, biology, imaging, and current guidelines. Randomized trials, prospective cohort studies, large multicenter retrospective series, systematic reviews, and current clinical practice guidelines were prioritized. KEY CONTENT AND FINDINGS: FLR augmentation with portal vein embolization or liver venous deprivation expands the pool of surgical candidates but requires careful interval management to limit disease progression. Thermal ablation can yield outcomes comparable to repeat resection in selected patients with small recurrent or solitary lesions; SBRT offers a non-invasive option for centrally located or perihilar tumors not amenable to ablation. TACE and TARE achieve comparable survival in selected patients, with TARE often preferred for infiltrative, unilobar, or portal-vein-compromised disease. The strongest prospective evidence for LRT integration with first-line systemic chemotherapy comes from the MISPHEC trial of concomitant Y-90 SIRT plus gemcitabine/cisplatin, the PUMP-2 trial of hepatic arterial infusion pump floxuridine plus systemic gemcitabine/cisplatin, and pooled comparative analyses. Emerging retrospective data suggest a survival benefit when LRT is added to first-line chemoimmunotherapy, but prospective confirmation is awaited. CONCLUSIONS: LRTs have evolved from salvage interventions to integral components of multidisciplinary iCCA care. Stage-stratified, biology-informed selection and integration with modern systemic backbones offer the most promising path forward. Prospective, modality-stratified trials with standardized endpoints are needed to translate promising signals into evidence-based practice.