Neoadjuvant Strategies for Patients with Resectable Biliary Tract Cancers: A Review

Cholangiocarcinoma (CC) is a rare and aggressive malignancy that arises from the epithelial cells (cholangiocytes) of the biliary tree. Biliary tract cancers (BTC) include both CC and gall bladder cancer. Surgical resection is considered the only curative treatment. Recently, however, a fundamental shift in the understanding of the molecular profiles of these tumors has led to a molecular-targeted approach with improved survival rates in some patients with these tumors. In patients with local or limited regional disease, neoadjuvant therapies offer a way to downstage tumors, assess tumor biology, potentially achieve R0 resection, and potentially prevent both locoregional and distant recurrence by treating occult micrometastatic disease. Because BTC are rare and surgery is the standard of care for patients with non-metastatic disease, there is very little data evaluating neoadjuvant strategies in resectable disease. Immunotherapies and molecularly targeted agents originally developed for advanced disease in the adjuvant or palliative settings are now being considered for neoadjuvant use. This review aims to summarize the data and provide a rationale for the role of neoadjuvant treatment in patients with resectable BTC. While there is no high-level evidence, studies show that neoadjuvant therapy that incorporates targeted treatments and immunotherapies under multidisciplinary oversight benefits select patients and is a valuable tool in the treatment of BTC. We favor molecular testing to guide neoadjuvant therapy for patients with BTC, when feasible, to prevent unnecessary operations and minimize the risk of recurrence or metastasis.