Liquid Biopsy Could Accelerate Precision Oncology in Advanced Biliary Tract Cancer: Clinical Cancer Research | October 2026

What Did the Study Find?

This study evaluated ctDNA next-generation sequencing (NGS) as an alternative to tissue profiling in advanced biliary tract cancer (aBTC), addressing a major practical problem: tissue is frequently inadequate or difficult to obtain.

• The global analysis included 10,937 patients, showing that ctDNA captured a molecular landscape broadly comparable with tissue sequencing, including clinically actionable ESCAT alterations.
• In an independent Spanish cohort of 126 patients, successful molecular profiling was available in 90% with ctDNA versus only 50% with tissue NGS.
• Results were substantially faster: median turnaround time was 8 days with ctDNA vs 27 days with tissue.
• Overall concordance for actionable ESCAT alterations was 83%.
• Importantly, concordance for FGFR2 fusions was 80%, supporting liquid biopsy even for therapeutically important structural alterations.
• ctDNA also carried prognostic information: median OS was 27.7 months with undetectable ctDNA, 18.5 months with low burden and 13.6 months with high ctDNA burden.
• A small subgroup receiving ESCAT-matched targeted therapy appeared to have longer survival, although the study was not designed to prove treatment benefit.

Why Does It Matter?

Advanced BTC has become an increasingly biomarker-driven disease, but precision treatment only works if molecular alterations are identified quickly enough for patients to receive targeted therapy. Waiting weeks for tissue, repeating biopsies or obtaining insufficient specimens can mean losing that therapeutic window.

GastroAGI Takeaway

In advanced biliary tract cancer, “no adequate tissue” should no longer mean “no molecular profiling.”

ctDNA NGS provided more frequent successful testing (90% vs 50%) and results about three times faster (8 vs 27 days) while maintaining good concordance with tissue for actionable alterations.

The practical implication is important: molecular profiling should be performed early in advanced BTC, and ctDNA can serve as a highly practical complementary—or when tissue is inadequate, alternative—NGS strategy.