PancreaSeq Genomic Classifier (PancreaSeq GC) Improves Pancreatic Cyst Classification and Detection of Advanced Neoplasia: A Multi-institutional Validation Study.

Abstract

The preoperative classification of pancreatic cysts and detection of advanced neoplasia (high-grade dysplasia/pancreatic ductal adenocarcinoma [PDAC]) represents a significant diagnostic challenge. A prospective, multi-institutional study found that DNA-based testing (PancreaSeq) of pancreatic cyst fluid (PCF) improved the assessment of pancreatic cysts. Notable imitations to PancreaSeq necessitated the development of a DNA/RNA-based panel called PancreaSeq Genomic Classifier (GC). We validated PancreaSeq GC on a prospective patient cohort. PancreaSeq GC was blindly tested on a prospective cohort of 241 patients with diagnostic follow-up. The performance of PancreaSeq GC in this cohort, which included 186 mucinous cysts (97 with advanced neoplasia), was benchmarked against traditional diagnostics and its DNA-only predecessor, PancreaSeq. PancreaSeq GC achieved 94.6% sensitivity and 96.4% specificity (area under the curve [AUC] of 0.955) for mucinous cysts. In comparison, increased fluid viscosity, elevated carcinoembryonic antigen (CEA), and PancreaSeq testing had lower sensitivities (71.4-88.2%) and lower AUC (0.824-0.941); however, PancreaSeq specificity was 100%. McNemar's test demonstrated higher sensitivity of PancreaSeq GC versus PancreaSeq for mucinous cysts (p < 0.001). For advanced neoplasia, PancreaSeq GC had 86.6% sensitivity and 97.9% specificity (AUC of 0.923), with McNemar's test confirming improved sensitivity over PancreaSeq (p = 0.031). Worrisome features, malignant cytopathology, and high-risk stigmata had lower sensitivities (44.3-84.5%) and lower AUC (0.604-0.892), while PancreaSeq had identical specificity to PancreaSeq GC. PancreaSeq GC had high accuracy in classifying intraductal oncocytic papillary neoplasms (IOPNs), intraductal tubulopapillary neoplasms (ITPNs), and cystic pancreatic neuroendocrine tumors (cPanNETs), with 97.1-100% sensitivity and 100% specificity. This validation study demonstrates statistically significant improvements in PancreaSeq GC for mucinous cysts and advanced neoplasia, establishing it as a clinically valuable tool for the preoperative evaluation of pancreatic cysts.