Chemoradiation of locally advanced biliary cancer: A PRISMA‐compliant systematic review

Introduction Biliary tract cancers (BTC) are rare and aggressive neoplasms. The current management of locally advanced or unresectable BTC is primarily based on chemotherapy (CHT) alone, linked to a median overall survival (OS) of approximately 12 months. However, international guidelines still consider concurrent chemoradiation (CRT) as an alternative treatment option. This study aims to review the current evidence on “modern” CRT for primary or recurrent unresectable BTC. Materials and Methods A comprehensive search was conducted on PubMed, Scopus, and Cochrane Library to identify relevant papers. Prospective or retrospective trials reporting outcomes after concurrent CRT of unresectable non‐metastatic, primary, or recurrent BTC were included. Only English‐written papers published between January 2010 and June 2022 were considered. Results Seventeen papers, comprising a total of 1961 patients, were included in the analysis. Among them, 11 papers focused solely on patients with primary unresectable BTC, while two papers included patients with isolated local recurrences and four papers encompassed both settings. In terms of tumor location, 12 papers included patients with intrahepatic, extrahepatic, and hilar BTC, as well as gallbladder cancer. The median CRT dose delivered was 50.4 Gy (range: 45.0–72.6 Gy) using conventional fractionation. Concurrent CHT primarily consisted of 5‐Fluorouracil or Gemcitabine. The pooled rates of 1‐year progression‐free survival (PFS) and OS were 40.9% and 56.2%, respectively. The median 1‐ and 2‐year OS rates were 63.1% and 29.4%, respectively. Grade ≥3 acute gastrointestinal toxicity ranged from 5.6% to 22.2% (median: 10.9%), while grade ≥3 hematological toxicity ranged from 1.6% to 50.0% (median: 21.7%). Conclusion Concurrent CRT is a viable alternative to standard CHT in patients with locally advanced BTC, offering comparable OS and PFS rates, along with an acceptable toxicity profile. However, prospective trials are needed to validate and further explore these findings. This is a systematic review of the current evidence on “modern” chemoradiation for primary or recurrent unresectable biliary tract cancers. We have critically compared chemoradiation outcomes with those of other treatment options, seeking to determine whether specific chemoradiation modalities provide distinct advantages in terms of treatment efficacy and patient safety. This analysis is pivotal for informing future treatment guidelines and optimizing pa