Utility of archived EUS-guided fine-needle biopsy samples for next-generation sequencing in pancreatic adenocarcinoma

Background and Objectives: Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy with limited treatment options. Comprehensive molecular profiling with next-generation sequencing (NGS) may enable personalized therapies, but its feasibility using EUS-guided fine-needle biopsy (EUS-guided FNB) and broad panels in routine practice remains unclear. This study aimed to assess the feasibility of NGS using residual diagnostic tissue from EUS-guided FNB in PDAC, without dedicated sampling. Methods: We performed a retrospective single-center study of patients with PDAC who underwent EUS-guided FNB, analyzing residual paraffin-embedded tissue blocks for NGS using a 63-gene panel. Samples required a minimum tumor cellularity of 20% and tumor area ≥10 mm 2 . Baseline, procedural, and genomic data were compared between NGS-feasible and NGS-unfeasible groups. The primary endpoint was technical success. Results: Thirty-five patients were included. NGS was successful in 74.3% of cases (26/35) using residual diagnostic material without additional biopsy passes. No significant baseline or procedural differences were observed between groups, except for metastatic disease, which was more frequent in the NGS-unfeasible group (55.6% vs . 11.5%, P = 0.029). KRAS mutations were identified in 73.1% of sequenced cases, predominantly at codon 12. Conclusion: EUS-guided FNB samples can support NGS from residual diagnostic tissue with high feasibility, avoiding dedicated sampling. This pragmatic approach may streamline molecular profiling and expand access to precision oncology in PDAC.