Translational and Implementation Barrier in the Management of Biliary Tract Cancer: Diagnostic, Molecular, Therapeutic, and Patient‐Centered Challenges

Biliary tract cancer (BTC) is a rare but highly lethal form of cancer and is frequently diagnosed at a late stage, thus limiting treatment options and prognosis. Although there have been great strides in the field of oncology, there are still a number of obstacles that stand in the way of improving patient care. Unfortunately, early diagnosis is still challenging due to the absence of sensitive biomarkers and effective screening strategies. Limited therapeutic options are also available, in which a small number of patients with molecular changes (IDH1/2, FGFR2, EGFR, HER2) benefit from FDA-approved targeted therapies. Despite the advent of less invasive and image-guided surgery, low resectability rates and important technical difficulties limit the use of surgery as the only potentially curative treatment. This review is dedicated to discussing the barriers to the effective translation of recent scientific advances into routine BTC management, including both translation and implementation. Issues of delayed diagnosis, limited tissue sampling for molecular analysis, limited availability of biomarker-driven therapies, and complex choice of surgery and local treatments are critical. Other barriers are weak multidisciplinary team (MDT) coordination, low rates of clinical trial participation, and lack of focus on patient-reported outcomes and quality of life. Existing preclinical models such as patient-derived xenografts (PDX) and patient-derived organoids (PDO) are unable to fully represent the molecular diversity of BTC and therefore are not useful for precision medicine. The molecular testing, adaptable clinical trial designs, multidisciplinary collaboration, and more patient-centered supportive care approaches will be needed to improve BTC outcomes.