Neoadjuvant Strategies for Liver Resection and Transplantation in Hilar and Intrahepatic Cholangiocarcinoma

Abstract: Cholangiocarcinoma (CCA) is an aggressive malignancy with limited curative options, often diagnosed at advanced stages. Even after R0 resection, recurrence rates remain high, prompting interest in neoadjuvant therapies to improve surgical outcomes. These approaches may enhance resectability, enable liver transplantation for initially unresectable cases, and improve long-term survival. A narrative review was conducted to synthesize the current evidence on neoadjuvant chemotherapy and radiotherapy protocols for patients with intrahepatic (iCCA) and perihilar cholangiocarcinoma (pCCA) undergoing liver resection or transplantation. Twenty-six studies, comprising 1,055 patients (668 iCCA, 387 pCCA), met the inclusion criteria. All patients received neoadjuvant therapy followed by resection (n = 655) or liver transplantation (n = 400). Chemotherapy, most commonly gemcitabine- and platinum-based, was used in most studies, often combined with radiotherapy modalities. Locoregional treatments, such as transarterial chemoembolization (TACE) and photodynamic therapy, were used less frequently. Reported median overall survival ranged from 22 to 54 months, with median recurrence-free survival from 7.1 to 55 months. Across studies, the 5-year survival ranged from 24% to 82%, and recurrence rates ranged from 0% to 55%. Heterogeneity in treatment protocols, patient selection, and outcome reporting limited direct comparisons. Neoadjuvant therapy shows promise for selected patients with iCCA and pCCA, improving resectability, enabling transplantation, and potentially enhancing survival. Multimodal regimens combining chemotherapy, radiotherapy, and locoregional treatments can achieve meaningful downstaging, but robust multicenter trials are needed to define optimal strategies.