Finding More in Less: Precision Medicine for Pancreatic Cancer Using Residual Cytology Samples

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal tumours and its incidence is increasing. Definitive diagnosis requires pathological confirmation. Cytology samples are obtained using endoscopic ultrasound-guided fine needle aspiration (EUS-FNA). The utility and storage conditions of residual liquid-based cytology (LBC) for PDAC remain poorly defined. METHODS: From 2020 to 2024, 268 patients were diagnosed with PDAC using EUS-FNA and LBC. Cell blocks were prepared when possible, and residual LBC samples were stored. RESULTS: Molecular studies were requested for 54 patients. Residual LBC was the only sample available in eight patients. Molecular analyses were requested at more than 2 months and up to 27 months after diagnosis in 31.7% of patients and performed on residual LBC or cell block based on availability and quality. Samples were not analysed in parallel. DNA concentration was higher in LBC than cell blocks, and MAPD (median absolute pairwise difference) was lower. LBC storage time did not affect NGS validity. Residual LBC provided an adequate proportion of valid studies in NGS DNA and MSI RT-PCR, showing no difference to cell blocks. RNA provided fewer valid studies, with no differences between sample types. The most frequently detected mutations were KRAS (35/41) and TP53 (12/41). No fusions or MSI were detected. CONCLUSIONS: In a real clinical setting, we show that residual LBC samples from PDAC are valid for molecular analysis, preserving the quality of nucleic acids. Residual LBC may be the only available sample and should be preserved to ensure patient access to targeted therapies.