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  • Review Article
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Perioperative approaches for patients with biliary tract cancer

Nature Reviews Clinical Oncology (2026)Cite this article

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Abstract

Biliary tract cancers, encompassing intrahepatic, perihilar and distal cholangiocarcinoma and gallbladder cancer, are a heterogeneous group of highly aggressive malignancies. Most patients have unresectable disease at first presentation, and even those who undergo surgery are likely to have disease recurrence. Newer approaches have included liver transplantation for selected patients, and the integration of locoregional and systemic therapies has expanded the number of patients who can benefit from surgery. The advent of immune-checkpoint inhibitors and targeted therapies for patients with advanced-stage disease has prompted the exploration of these agents in earlier-stage disease settings. Despite this progress, treatment algorithms remain complex, necessitating a multidisciplinary and individualized approach to patient management. Future research should focus on optimizing patient selection through biomarker-driven strategies, including the integration of molecular profiles to guide the selection of systemic therapy, as well as refining the criteria for surgery and transplantation. These improvements will require global collaboration and novel clinical trial designs. In this Review, we describe evolving perioperative strategies for the management of patients with biliary tract cancers and highlight emerging directions in the field.

Key points

  • Surgical resection remains the cornerstone of curative treatment of biliary tract cancer, although surgery is often only feasible in a minority of patients owing to late-stage presentation. The risk of recurrence remains high even after complete resection.

  • Liver transplantation is emerging as a curative option for selected patients with unresectable perihilar or intrahepatic cholangiocarcinoma, particularly when combined with neoadjuvant therapy and under strict eligibility criteria.

  • Capecitabine is the current standard-of-care adjuvant therapy; however, considerable research interest exists in neoadjuvant approaches designed to improve resectability and thus extend survival. In some protocols, adjuvant capecitabine is still administered following neoadjuvant therapy and surgery, depending on pathological findings and patient tolerance.

  • Immune-checkpoint inhibitors have demonstrated modest survival benefits in patients with advanced-stage disease, prompting exploration of the role of these agents in earlier-stage disease and/or in perioperative settings.

  • Molecular profiling is utilized in the advanced-stage disease setting for treatment selection, although earlier implementation might provide prognostic information and the opportunity to utilize targeted therapies at earlier disease stages.

  • The tumour microenvironment and immune landscape of biliary tract cancer pose challenges for the implementation of immune-checkpoint inhibitors but also provides key avenues for future biomarker development and therapeutic innovation.

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Fig. 1: Anatomical locations, surgical procedures and common molecular alterations for biliary tract cancer.
Fig. 2: Roadmap to future directions of perioperative care in patients with biliary tract cancer.

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Acknowledgements

The authors’ work is based on work from COST Action Precision-BTC-Network, CA22125, supported by COST (European Cooperation in Science and Technology).

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  1. These authors contributed equally: Grainne M. O’Kane, Gonzalo Sapisochin.

Authors and Affiliations

  1. University Health Network, HPB Surgical Oncology, Toronto, Ontario, Canada

    Anudari Zorigtbaatar, Zhihao Li, Christian T. J. Magyar, Laia Aceituno & Gonzalo Sapisochin

  2. Department of Surgery, University of Toronto, Toronto, Ontario, Canada

    Anudari Zorigtbaatar & Gonzalo Sapisochin

  3. Institute for Health Policy, Management, and Evaluation, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada

    Anudari Zorigtbaatar

  4. Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland

    Christian T. J. Magyar

  5. University Health Network, Transplant Hepatology, Toronto, Ontario, Canada

    Laia Aceituno & Arndt Vogel

  6. Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany

    Anna Saborowski & Arndt Vogel

  7. Princess Margaret Cancer Center, University Health Network, Toronto, Ontario, Canada

    Robert C. Grant & Grainne M. O’Kane

  8. Ontario Institute for Cancer Research, Toronto, Ontario, Canada

    Robert C. Grant

  9. St. Vincent’s University Hospital and School of Medicine, University College Dublin, Dublin, Republic of Ireland

    Grainne M. O’Kane

  10. Department of Abdominal, General Surgery and Liver Transplantation. CIRCATH Research Group, Vall d’Hebron Institut de Recerca, Barcelona, Spain

    Gonzalo Sapisochin

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All authors made a substantial contribution to all aspects of the preparation of the manuscript.

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Correspondence to Grainne M. O’Kane or Gonzalo Sapisochin.

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Competing interests

A.S. has acted as an adviser of Bristol Myers Squibb (BMS), Eisai, Incyte, Jazz Pharmaceuticals, MSD, Roche and Taiho, has received honoraria from Amgen, AstraZeneca, BMS, Eisai, Ipsen, Lilly, MSD, Roche and Servier, has received travel support from Eisai, Ipsen, MSD, Pierre-Fabre and Servier, and has served on the advisory boards of, and is a member of the Data and Safety Monitoring Board of Heparegenix. A.V. has acted as a consultant and/or adviser and has received honoraria from AstraZeneca, BeiGene, BMS, Boehringer Mannheim, BTG, EISAI, GSK, Incyte, Ipsen, Merck Sharpe & Dohme, Roche, Servier, Sirtex and Taiho. G.M.O.’K. has acted as a consultant and/or adviser of AstraZeneca, Roche, Servier and Zymeworks, has acted as a speaker on behalf of Merck Sharpe & Dohme, has received research grants from AstraZeneca and Roche, and has received travel support from Merck Sharpe & Dohme, Novartis, Roche and Takeda. G.S. has acted as a consultant of AstraZeneca, HepaRegeniX, Integra, Novartis and Roche, has acted as a speaker on behalf of AstraZeneca, Chiesi, Integra and Roche, has received research funding from Roche, has research collaborations with AstraZeneca, HeparegeniX, Natera, Roche and Stryker, and holds stock in Amgen, CVS Health, Gilead, Johnson & Johnson, Merck Sharpe & Dohme, Pfizer and UnitedHealth. All other authors declare no competing interests.

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Zorigtbaatar, A., Li, Z., Magyar, C.T.J. et al. Perioperative approaches for patients with biliary tract cancer. Nat Rev Clin Oncol (2026). https://doi.org/10.1038/s41571-026-01130-5

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