Young-onset biliary tract cancers: Characteristics, treatment patterns, and patient outcomes

The incidence of biliary tract cancers (BTC) among young individuals (≤50 years) is currently rising. We aimed to investigate the clinical, therapeutic and molecular characteristics and outcomes of young-onset BTC (YO-BTC).

Patients with histologically confirmed BTC treated at Gustave Roussy (France) and Vall d'Hebron Institute of Oncology (Spain) were categorized as YO-BTC (≤50 years old), average-onset (AO-BTC; 51-69 years old), and late-onset (LO-BTC; ≥70 years old). The primary endpoint was overall survival (OS). The secondary endpoint was the growth modulation index (GMI), e.g., the ratio of progression-free survival (PFS) with the targeted therapy line to the PFS of the n-1 line.

Among 1,023 patients with BTC, 184 (18%) had YO-BTC, 561 (54.8%) had AO-BTC, and 278 (27.2%) had LO-BTC. Median OS in metastatic patients was longer in the YO group (22 months; 95% CI 18-26) than in the AO group (18 months; 95% CI 17-20; p = 0.010) or LO group (15 months; 95% CI 13-17; p <0.001), despite a higher tumor burden in YO-BTC. FGFR2 fusions were more frequent in YO-BTC (12% vs. 5.7% AO and 4.3% LO; p = 0.038). Patients with YO-BTC received more targeted therapies as second or later lines (48%, 37%, and 29% for YO, AO, and LO; p = 0.020). Among patients receiving molecular-matched treatments, GMI >1.33 was more frequent in YO-BTC (61.1%, 39.2%, and 33.3% for YO, AO, and LO; p = 0.044), although no differences in PFS or OS were observed.

Patients with YO-BTC have improved outcomes in the metastatic setting. The YO-BTC group is enriched for FGFR2 fusions, highlighting opportunities for precision oncology-based approaches.

The study underscores the scientific justification for investigating age-related differences in biliary tract cancers, revealing that patients with young-onset biliary tract cancer have improved survival outcomes and a higher prevalence of actionable molecular alterations, particularly FGFR2 fusions. Physicians can apply these results by incorporating molecular profiling and targeted therapies earlier in the treatment plan for younger patients, potentially improving their prognosis and quality of life. However, it is crucial to consider the study's limitations, such as the retrospective design and potential selection bias, to avoid overgeneralization and ensure appropriate application of the findings in clinical practice and future research.