Pitfalls, challenges, and updates in adjuvant systemic treatment for resected biliary tract cancer

ABSTRACT

Introduction: Unfortunately, potentially curative surgical resection is possible in approximately the 25% of biliary tract cancer (BTC) patients at diagnosis, and even following radical surgery, relapse rates remain high. Thus, the role of adjuvant systemic treatment has been widely explored in this setting over the last decades, with the hope of lowering recurrence rates and improving outcomes of BTC patients.

Areas covered: In this review, we provide an overview of available evidence regarding adjuvant systemic therapy in resected BTC, critically discussing the pros and cons of recently published clinical trials such as the BILCAP, the BCAT, and the PRODIGE-12/ACCORD-18 phase III studies.

Expert opinion: Although the BILCAP trial has established adjuvant capecitabine for 6 months following radical resection as a novel standard of care, the role of adjuvant systemic chemotherapy is the object of debate and controversy in the BTC medical community. Although most of the international guidelines on BTC management have not yet been updated, the recently published ASCO guidelines support the use of capecitabine in this setting. Several phase I to III clinical trials are currently evaluating the role of novel therapeutic approaches in patients with resected BTC, and the results of these studies are highly awaited.

KEYWORDS:

• Biliary tract cancer
• cholangiocarcinoma
• capecitabine
• adjuvant treatment
• BILCAP

Article highlights

• Despite surgery performed with potentially curative intent, relapse rates are high in biliary tract cancer (BTC), with approximately 60-70% of the patients expected to experience disease recurrence.

• In view of high tumor recurrence, adjuvant treatments have been widely explored for many years, in the form of radiotherapy, chemotherapy, and chemo-radiotherapy.

• Since 2017, three randomized phase III clinical trials have been published, reporting conflicting results: the BCAT, the PRODIGE-12/ACCORD-18, and the BILCAP.

• Although the BILCAP reported a benefit in terms of overall survival, the results of this study have been a matter of debate in the BTC medical community.

• Herein, we summarize the current state-of-the-art regarding adjuvant systemic treatment for resected BTC, critically discussing the results of recent trials in this setting.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers in this manuscript have no relevant financial or other relationships to disclose.