Role of adjuvant and neoadjuvant therapy for resectable biliary tract cancer

ABSTRACT

Introduction: Although the safety of biliary tract cancer resection has improved over the years, the recurrence rate is still high, and the postoperative prognosis remains low after biliary tract cancer resection. Therefore, the development of effective adjuvant therapy is essential to improve treatment outcomes. Because biliary tract cancer is rare compared with other gastrointestinal cancers, there have been only a small number of clinical trials of adjuvant therapy. However, in recent years, the results of several large-scale randomized controlled trials have been published, and clinical trials investigating the efficacy of new regimens are currently ongoing.

Areas covered: This review presents the results of previously published important phase II and III clinical trials of adjuvant and neoadjuvant therapy for biliary tract cancer and discusses their interpretation. The future direction of new research on resectable biliary tract cancer treatment is also discussed.

Expert opinion: The foundations of large-scale clinical trials of adjuvant and neoadjuvant therapy for biliary tract cancer are underway, and new trials will establish evidence of their effectiveness. Additionally, breakthroughs in treatment through genetic and molecular research are expected.

KEYWORDS:

• Adjuvant therapy
• bile duct cancer
• biliary tract cancer
• cholangiocarcinoma
• clinical trial
• neoadjuvant therapy

Article highlights

• The postoperative prognosis of patients with lymph node metastasis-positive, R1 resection, or stage II or higher biliary tract cancer is poor. The development of effective adjuvant/neoadjuvant therapy is important to improve the outcome of these patients.

• For many years, surgery alone has been the standard of care for patients with resectable biliary tract cancer. However, the results of the BILCAP study implied that adjuvant capecitabine therapy prolongs overall survival after surgery.

• In addition to the BILCAP study, recently published phase II trials suggest that oral fluoropyrimidine may be effective as adjuvant chemotherapy for biliary tract cancer.

• JCOG1202 (ASCOT) and ACTICCA-1 are ongoing phase III trials of adjuvant therapy in biliary tract cancer.

• Evidence on the efficacy of adjuvant chemoradiation is limited due to a lack of phase III trial data.

• The GAIN trial and JCOG1920 (NABICAT) are ongoing phase III studies of neoadjuvant therapy in biliary tract cancer.

• The current focus of biliary tract cancer research has shifted to genetic analysis, and it is expected that circulating tumor cells and circulating DNA (ctDNA) will become new markers for diagnosis and treatment.

Acknowledgments

We thank Dr. H. Nikki March, PhD, from Edanz Group for editing a draft of this manuscript.

Reviewer disclosures

One reviewer would like to disclose that they are the coordinating investigator of a trial discussed in this paper. All other peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

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.

Additional information

Funding

This paper was not funded.