METHODS article
Front. Oncol.
Sec. Gastrointestinal Cancers: Hepato Pancreatic Biliary Cancers
Ablatio-bilica: Safety of biliary intraductal radiofrequency ablation in patients with unresectable extrahepatic biliary tract cancer undergoing systemic -anti-tumor therapy: a phase II, multi-center, randomized, and controlled study
Provisionally accepted
- 1University Hospital of Bern, Bern, Switzerland
- 2University of Bern, Bern, Bern, Switzerland
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Background: Unresectable and/or metastatic biliary tract cancer (EBTC) presents a clinical challenge with high mortality rates despite therapeutic advancements, e.g. chemotherapy + immune checkpoint inhibitors (CICI). One critical aspect is biliary obstruction, which compromises liver function, associates with complications and limits the applicability of systemic treatment (chemotherapy with or without immune checkpoint inhibitors (ICI). Endoscopic interventions with stent placement alleviate biliary obstruction and hence, are standard of care. However, stent patency issues and tumor progression remain challenges, prompting the exploration of adjunctive therapies. Biliary radiofrequency ablation (bRFA) induces local tumor destruction, improves stent patency and potentially boosts the immune response against cancer cells being synergistic with CICI. Randomized controlled trials (RCT) demonstrated improved overall survival in EBTC but have not been performed in the setting of CICI and have not focused on rate and severity of adverse events (AE). Nonetheless, multiple current meta-analyses propose the use of bRFA in malignant biliary obstruction without high-quality data on its safety in combination with CICI. Hypothesis: We hypothesize that bRFA in patients with unresectable and/or metastatic EBTC undergoing systemic treatment (chemotherapy with or without immunotherapy) is safe. Methods: This is a randomized-controlled clinical trial (RCT) comparing chemotherapy with or without ICI plus endoscopic stenting (n=12) versus chemotherapy with or without ICI plus endoscopic stenting and bRFA (n=24) being allocated in a 1:2 ratio. The primary endpoint is the proportion of severe treatment-related adverse events (grade 3 or 4) leading to permanent discontinuation of all active chemotherapeutic drugs up to six months after enrolment. Discussion: Our findings will provide valuable insights into the role of bRFA as a supplementary treatment in unresectable and/or metastatic EBTC in conjunction with systemic treatment. In case, this safety-study does indicate no clinically relevant increase in severe adverse events in EBTC treated with systemic treatment then an RCT addressing the efficacy of bRFA in terms of progression-free and overall survival in this setting will follow. Trial registration: ClinicalTrials.gov, NCT06274879 Funding: Swiss Cancer Research (KFS-5812-02-2023)
Keywords: Extrahepatic biliary duct cancers, Immuncheckpoint inhibitor, Phase II trial, Radiofrecuency ablation, Safety
Received: 19 Feb 2025; Accepted: 28 Nov 2025.
Copyright: © 2025 Pfister, Chan, Trelle, Moser, Berger and Wiest. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Reiner Wiest
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.