Adjuvant treatment in biliary tract cancer: To treat or not to treat?

Abstract

Biliary tract cancer is a rare malignant tumor. There is limited knowledge about biology and natural history of this disease and considerable uncertainty remains regarding its optimal diagnostic and therapeutic management. The role of adjuvant therapy is object of debate and controversy. Although resection is identified as the most effective and the only potentially curative treatment, there is no consensus on the impact of adjuvant chemotherapy and/or radiotherapy on the high incidence of disease recurrence and on survival. This is mainly due to the rarity of this disease and the consequent difficulty in performing randomized trials. The only two prospectively controlled trials concluded that adjuvant chemotherapy did not improve survival. Most of the retrospective trials, which had limited sample size and included heterogeneous patients population and non-standardized therapies, suggested a marginal benefit of chemoradiotherapy in reducing locoregional recurrence and an uncertain impact on survival. Welldesigned multi-institutional randomized trials are necessary to clarify the role of adjuvant therapy. Two ongoing phase Ⅲ trials may provide relevant information.

Prognostic significance of thymidylate synthase, thymidine phosphorylase and dihydropyrimidine dehydrogenase expression in biliary tract cancer patients receiving adjuvant 5-fluorouracil-based chemotherapy

“…It is difficult to elucidate the efficacy of adjuvant chemotherapy for each type of tumor, due to the limited number of patients (4,5). To the best of our knowledge, there are currently only two RCTs available on adjuvant chemotherapy in BTC patients (6,7).…”

“…5-FU is the most extensively investigated drug for BTC, as a single agent or in combination with other treatment modalities (4)(5)(6)(7). Several mechanisms of resistance to 5-FU were reported in cholangiocarcinoma cell lines.…”

“…The majority of the retrospective trials, which included limited sample sizes, heterogeneous patient populations and non-standardized therapies, suggested a marginal benefit of chemotherapy in reducing recurrence and an uncertain effect on survival (4,5). The only two prospective randomized controlled trials (RCT) currently available concluded that adjuvant chemotherapy did not improve survival (6,7).…”

Hepatobiliary Cancers, Version 2.2014

“…Nevertheless, the role of adjuvant chemotherapy or chemoradiation therapy in patients with resected biliary tract cancers is poorly defined. 138 Because of the low incidence of biliary tract cancers, the efficacy and safety of adjuvant chemotherapy or chemoradiation therapy has been evaluated mostly in retrospective studies that have included only a small number of patients; these studies often combined patients with gallbladder and bile duct cancers, with a few exceptions. Despite the chal-lenges associated with accruing large numbers of patients with biliary tract cancer for randomized phase III trials, it is widely recognized that efforts should be made to conduct studies in which the individual disease entities are evaluated separately.…”

Place de la chimiothérapie dans la prise en charge des cancers des voies biliaires

“…Il a été étudié dans de rares séries rétrospec-tives à faible effectifs associant cholangiocarcinomes et autres cancers des voies biliaires [2].…”