Management of biliary tract cancers in early-onset patients: A nested multicenter retrospective study of the ACABI GERCOR PRONOBIL cohort

Liver Int. 2024 Aug;44(8):1886-1899. doi: 10.1111/liv.15922. Epub 2024 Apr 8.

Abstract

Background & aims: Accumulating data has shown the rising incidence and poor prognosis of early-onset gastrointestinal cancers, but few data exist on biliary tract cancers (BTC). We aimed to analyse the clinico-pathological, molecular, therapeutic characteristics and prognosis of patients with early onset BTC (EOBTC, age ≤50 years at diagnosis), versus olders.

Methods: We analysed patients diagnosed with intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, and gallbladder adenocarcinoma between 1 January 2003 and 30 June 2021. Baseline characteristics and treatment were described in each group and compared. Progression-free survival, overall survival and disease-free survival were estimated in each group using the Kaplan-Meier method.

Results: Overall, 1256 patients were included, 188 (15%) with EOBTC. Patients with EOBTC demonstrated fewer comorbidities (63.5% vs. 84.5%, p < .0001), higher tumour stage (cT3-4: 50.0% vs. 32.3%, p = .0162), bilobar liver involvement (47.8% vs. 32.1%, p = .0002), and metastatic disease (67.6% vs. 57.5%, p = .0097) compared to older. Patients with EOBTC received second-line therapy more frequently (89.5% vs. 81.0% non-EOBTC, p = .0224). For unresectable patients with BTC, median overall survival was 17.0 vs. 16.2 months (p = .0876), and median progression-free survival was 5.8 vs. 6.0 months (p = .8293), in EOBTC vs. older. In advanced stages, fewer actionable alterations were found in EOBTC (e.g., IDH1 mutations [7.8% vs. 16.6%]; FGFR2-fusion [11.7% vs. 8.9%]; p = .029).

Conclusions: Patients with EOBTC have a more advanced disease at diagnosis, are treated more heavily at an advanced stage but show similar survival. A distinctive molecular profile enriched for FGRF2 fusions was found.

Keywords: biliary tract cancers; chemotherapy; cholangiocarcinoma; early onset; molecular testing.

Publication types

  • Multicenter Study

MeSH terms

  • Adenocarcinoma / mortality
  • Adenocarcinoma / pathology
  • Adenocarcinoma / therapy
  • Adult
  • Age of Onset
  • Aged
  • Bile Duct Neoplasms / mortality
  • Bile Duct Neoplasms / pathology
  • Bile Duct Neoplasms / therapy
  • Biliary Tract Neoplasms* / mortality
  • Biliary Tract Neoplasms* / pathology
  • Biliary Tract Neoplasms* / therapy
  • Cholangiocarcinoma* / mortality
  • Cholangiocarcinoma* / pathology
  • Cholangiocarcinoma* / therapy
  • Female
  • Gallbladder Neoplasms / mortality
  • Gallbladder Neoplasms / pathology
  • Gallbladder Neoplasms / therapy
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Prognosis
  • Progression-Free Survival
  • Retrospective Studies