Locoregional Therapy Is Moving From Adjunct to Strategy in Cholangiocarcinoma
Unresectable and advanced cholangiocarcinoma still begins with a difficult benchmark: systemic chemotherapy combined with immunotherapy produces a median overall survival of 13 months, with a 3-year overall survival of 15%. Against that backdrop, locoregional therapy is no longer a peripheral concept. It is being tested as a way to slow tumor growth inside the liver, preserve hepatic function, and create a wider therapeutic window for patients who cannot undergo curative resection.
This narrative review pulled together clinical studies of locoregional approaches in intrahepatic and perihilar cholangiocarcinoma, with emphasis on patients whose disease remained localized enough to consider regional control but who were not surgical candidates. The literature search centered on PubMed and MEDLINE, while ongoing and completed trials were tracked through ClinicalTrials.gov. The clinical message is compact but important: the field has accumulated enough signal to justify individualized use, yet not enough randomized evidence to flatten treatment into a single algorithm.
One sentence captures the current tension. The strongest data are still scattered across small studies, retrospective cohorts, and phase-oriented programs rather than head-to-head trials.
Intrahepatic Disease Has the Widest Locoregional Toolbox
For intrahepatic cholangiocarcinoma (iCCA), the reviewed studies span a broad set of regional interventions. Percutaneous image-guided local ablation has been assessed using radiofrequency ablation and microwave ablation, with a reported 3-year overall survival of 42%. Cryoablation, interstitial electroporation, and brachytherapy have also been explored, reflecting the practical need to attack tumors directly when surgery is off the table. Each of these approaches aims to exploit local tumor anatomy: destroy visible lesions, reduce viable tumor burden, and limit the amount of untreated disease that can seed progression elsewhere in the liver.
External beam radiotherapy has also shown a place in iCCA, particularly when delivered with high-precision techniques. The review cites a 3-year overall survival of 38% for these approaches. In practice, that matters because modern radiotherapy can shape dose around critical vascular and biliary structures, making local control more plausible in anatomy that once seemed too unforgiving for radiation. The biologic rationale is straightforward: regional radiation can sterilize microscopic extension around the dominant lesion and may delay local hepatic failure even when metastatic biology remains a threat.
A second path runs through the hepatic arterial tree. Intra-arterial therapy has included transarterial chemoembolisation with a 3-year overall survival of 17%, selective internal radioembolisation with a 3-year overall survival of 40%, and floxuridine delivery through a hepatic arterial infusion pump with a reported 3-year overall survival range of 26% to 50%. These numbers cannot be compared as if they came from identical populations. They likely reflect different eras, patient selection, tumor burden, liver reserve, and treatment intent. Still, they show that regional vascular targeting can produce meaningful disease control in a subset of patients whose cancer remains liver-dominant.
Perihilar Tumors Put Radiotherapy at the Center of Regional Care
For perihilar cholangiocarcinoma (pCCA), external beam radiotherapy has been studied in three distinct settings. As definitive therapy, the review cites a 1-year overall survival of 100%. As adjuvant postoperative therapy, 3-year overall survival reached 58%. As neoadjuvant therapy before liver transplantation, 3-year overall survival was 62%. Those are not interchangeable clinical scenarios, and they should not be read as competing estimates of the same strategy. They reflect different goals: local disease control, postoperative risk reduction, and selection or bridging toward transplant in carefully chosen patients.
The relevance of these data lies in anatomy and biology. Perihilar tumors often grow in close proximity to the bile ducts and portal structures, where complete surgical clearance is difficult and where local progression can be devastating. Radiotherapy, when deployed precisely, offers a way to manage that local threat without relying solely on systemic therapy to control a disease that is frequently concentrated in the hilum. In transplant-based strategies, the radiotherapy signal also suggests that local treatment may help keep disease within transplant criteria long enough for definitive intervention.
Combination Therapy Is Becoming the Organizing Principle
Recent and ongoing trials increasingly combine locoregional treatment with standard systemic therapy rather than asking one modality to replace the other. This is the most clinically important trend in the review. Cholangiocarcinoma rarely behaves like a purely local cancer, yet many patients present with disease that is still heavily liver-dominant. A combined approach makes biological sense: systemic therapy addresses occult micrometastatic spread, while locoregional therapy suppresses the dominant intrahepatic tumor burden that often drives liver failure and symptom progression.
The review makes clear, however, that the field is still short on randomized controlled trials. Without them, cross-trial comparisons remain vulnerable to selection bias, stage migration, and differences in liver function or tumor distribution at baseline. Patients selected for ablation, radioembolization, or transplant-linked radiotherapy are often those most likely to benefit from regional control in the first place. That makes the reported survival figures clinically useful, but not definitive proof of superiority over systemic therapy alone.
Multidisciplinary Selection Will Decide Who Benefits
For now, treatment planning in unresectable or advanced cholangiocarcinoma needs to remain individualized. Flexible, staged combinations of locoregional and systemic therapies fit the evidence better than a rigid sequence. In one patient, that may mean ablation of a dominant iCCA lesion followed by systemic therapy. In another, it may mean high-precision radiotherapy or radioembolization to stabilize liver-dominant disease before reassessment. In pCCA, neoadjuvant radiotherapy may function as a bridge to transplant in carefully screened candidates.
A multidisciplinary tumour board is central to those decisions. Hepatobiliary surgeons, interventional radiologists, radiation oncologists, medical oncologists, and transplant specialists all contribute different constraints and opportunities, and the treatment plan often depends as much on liver function and anatomy as on tumor histology. This is especially true in cholangiocarcinoma, where ductal involvement, vascular proximity, and biliary obstruction can narrow the safe options faster than the cancer itself.
The major limitation is not the absence of activity signals. It is the scarcity of randomized evidence capable of telling clinicians which locoregional sequence improves survival, which patients should be excluded, and whether combination therapy should be introduced earlier rather than later. Until those data arrive, locoregional treatment remains a carefully selected tool rather than a universal standard, and its use should track the biology of the tumor as closely as the availability of the procedure.