Endoscopic Ultrasound Molecular Evaluation of Pancreatic Cancer Trial to profile molecular landscape of inoperable pancreatic ductal adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) is a poor prognostic malignancy. Comprehensive genomic profiling (CGP) has improved outcomes in many cancers, but widespread uptake in PDAC remains elusive. This study investigated the feasibility of using endoscopic ultrasound with fine-needle biopsy (EUS-FNB) for CGP in advanced PDAC. Patients and methods (Experimental Design): A multi-centre prospective cohort study was conducted to assess the feasibility of using DNA and RNA extracted from fresh frozen or archival formalin-fixed paraffin-embedded (FFPE) EUS-FNB for CGP on advanced PDAC using the TSO-500 gene panel testing. The results of the CGP were reviewed at a molecular tumour board (MTB) and subsequent treatment recommendations forwarded to the referring clinicians. Results CGP was successful in 129/143 (90%) patients enrolled between May 2020 to September 2023. Fresh frozen EUS-FNB provided suitable genetic material for CGP in 123/133 (92%) patients. Conversely, CGP was successful on FFPE biopsy blocks from only 6/16 (38%) patients. 52/143 (36%) patients had a potentially targetable mutation detected, and 8 (6%) of these patients were treated with targeted therapy based on their EUS-FNB-derived molecular profile. Patients who received personalised therapy had a significant (p<0.0001) increase in survival versus standard or no therapy at 12-months and 36-months. Median patient survival on standard therapy was 9.47 months versus >18-months for personalised therapy. Conclusion This real-world study confirms the feasibility and utility of CGP using EUS-FNB in advanced PDAC. It illustrates the importance of timely access to personalised therapy informed by CGP, which can impact the treatment pathway and improve survival outcomes.