Perioperative Strategies Are Redefining Curative Pathways in Biliary Tract Cancer Nature Reviews Clinical Oncology | March 2026

Introduction

Biliary tract cancers (BTCs), including intrahepatic, perihilar and distal cholangiocarcinoma as well as gallbladder cancer, remain among the most aggressive gastrointestinal malignancies. Curative treatment has traditionally relied on surgical resection, yet most patients present with advanced disease, limiting operability. Even after complete resection, recurrence is common, underscoring the need for more effective perioperative strategies to improve long-term outcomes.

Problem Statement

Management of BTC in the perioperative setting remains challenging owing to disease heterogeneity, frequent late-stage presentation, and high postoperative recurrence rates. While surgery remains the only established curative option, its benefit is limited by strict resectability criteria and poor long-term disease control. The central challenge is how to safely expand curative-intent treatment through better patient selection, integration of systemic and locoregional therapies, and refinement of transplantation strategies.

Summary

This review outlines the evolving perioperative landscape in BTC, emphasizing a shift from surgery alone toward a more integrated, multidisciplinary treatment model. Surgical resection remains the cornerstone of curative therapy, with adjuvant capecitabine continuing as the current standard after resection. However, increasing emphasis is being placed on neoadjuvant strategies to improve resectability and optimize oncologic outcomes. Liver transplantation is emerging as a promising curative option in highly selected patients with unresectable perihilar or intrahepatic cholangiocarcinoma, particularly when paired with neoadjuvant therapy and rigorous selection criteria. The review also highlights the growing relevance of immune-checkpoint inhibitors and targeted therapies, which have shown benefit in advanced disease and are now being explored in earlier-stage and perioperative settings. Importantly, earlier molecular profiling may refine prognostication and enable biomarker-guided treatment selection before surgery. Overall, perioperative BTC management is moving toward precision-based, individualized care, where multimodal therapy and biologic stratification are expected to play a central role in expanding curative opportunities.