Past, Present, and Future Management of Localized Biliary Tract Malignancies

The group of biliary tract malignancies covered in this article-including GBC, iCCA, and pCCA-often present at an advanced stage with metastatic or unresectable disease. Patients are rarely cured without a having margin-negative surgical resection that is now often accompanied by a portal lymphadenectomy for staging. Although biliary malignancies have historically been grouped together in clinical trials, they are genetically heterogenous with distinct mutational drivers rendering them sensitive to specific targeted therapies. Adjuvant therapy for patients BTC resected with curative intent is capecitabine for 24 weeks (8 cycles) based on the BILCAP trial.(41) Several disease-specific neoadjuvant and peri-operative trials are underway with the potential to incorporate combinatorial therapy with cytotoxic and targeted inhibitors. Integrating liver-directed therapy with HAI and combined with systemic therapy can control hepatic disease and facilitate conversion to resection in 10% of patients with initially unresectable iCCA. As our understanding of the unique biology driving the family of biliary tract malignancies continues to evolve, we anticipate an ongoing evolution of a personalized therapy approach rendering more patients these rare cancers candidates for surgical resection and ultimately cure of their disease.