Clinical utility of incorporating next-generation sequencing results in the management algorithm of pancreatic cysts

Abstract

Background and Aims

Pancreatic cysts often pose challenges in predicting malignant progression. Next-generation sequencing (NGS) has become an appealing ancillary diagnostic test. The diagnostic performance is well characterized, but the impact on clinical management remains unclear. We evaluated the efficacy of integrating NGS into cyst management algorithms.

Methods

This single-center retrospective study included 441 adult patients who were seen at our high-risk pancreatic lesion clinic between 2016 and 2022 and had NGS data available. Performance characteristics of PancreaSeq (University of Pittsburgh Medical Center, Pittsburgh, Pa, USA) were calculated. The clinical utility of PancreaSeq in guiding surgical management and differentiating cyst type was evaluated.

Results

Twenty-five high-risk mutations demonstrated a sensitivity of 72.7% (95% confidence interval [CI], 49.8-89.3), a specificity of 97.8% (95% CI, 96-99), and an area under the receiver-operating characteristic curve of .85 (95% CI, .76-.95) in predicting advanced neoplasia. NGS detected KRAS or GNAS mutations in 179 of 324 patients (55.3%) and VHL mutations in 15 of 324 patients (3.4%) with unclear cyst types, facilitating the decision regarding surveillance versus clinic discharge. Among 27 patients with isolated pancreatic duct dilation, 12 (48.1%) had mutations consistent with mucinous neoplasms leading to a diagnosis of main duct intraductal papillary mucinous neoplasm. These findings resulted in surgical management for 6 patients. Overall, 115 of 441 patients (26.1%) had some management change after undergoing NGS.

Conclusions

NGS informed surgical decision-making, cyst type differentiation, and evaluation of pancreatic duct dilation, leading to changes in management. Indeed, NGS emerged as a useful tool in select patients with pancreatic lesions by improving diagnostic precision and guiding patient care paths.