Epidemiology, biomarkers, and therapeutic approach in early-stage biliary tract cancers

Biliary tract cancer (BTC) represents a heterogeneous group of malignancies, including intrahepatic, perihilar, and distal cholangiocarcinoma, as well as gallbladder cancer. Surgical resection is the only potential curative treatment for early-stage BTC, though outcomes with surgery alone were poor, with high rates of recurrence. In recent years, studies of adjuvant chemotherapy with capecitabine or S-1 have shown improved survival compared to postoperative observation alone. Ongoing clinical trials are incorporating multiple treatment modalities, including radiotherapy, immunotherapy, and targeted therapy. For instance, building on the success of chemo-immunotherapy in the metastatic setting, trials are testing similar designs as adjuvant treatment. The utility of targeted therapies against genetic alterations like FGFR2, IDH1, KRAS, HER2, and SMAD4 in advanced BTC has also spurred exploration of targeted therapy for early-stage BTCs. Various treatment regimens are now also being tested in the neoadjuvant treatment and perioperative setting. The goal of these treatment strategies is to improve surgical outcomes and identify new modalities to reduce recurrence rates of early-stage BTCs. This review provides an overview of the current management landscape of early-stage BTC, presenting the epidemiology and risk factors, reviewing the current management paradigm, and highlighting emerging therapeutic strategies.