Abstract
Introduction Indeterminate cytology occurs in a significant number of patients with solid pancreaticobiliary lesion that undergo endoscopic ultrasonography fine needle aspiration or endoscopic retrograde cholangio-pancreatography and can incur further expensive testing and inappropriate surgical intervention. Mutation profiling improves diagnostic accuracy and yield but the impact on clinical management is uncertain. We determined the performance of mutation profiling in clinical practice and its impact on management in solid pancreaticobiliary patients with indeterminate cytology. Methods Solid pancreaticobiliary patients with non-diagnostic, benign, atypical or suspicious cytology who had past mutation profiling testing were included. Mutation profiling examined KRAS mutation and a tumor suppressor gene associated loss of heterozygosity mutation panel covering 10 genomic loci. Two endosonographers made management recommendations without and then with mutation profiling results, indicating their level of confidence. Results Mutation profiling improved diagnostic accuracy in 232 patients with indeterminate cytology. Among patients with non-diagnostic cytology, low risk mutation profiling provided high specificity and negative predictive value for the absence of malignancy while high risk mutation profiling identified malignancies otherwise undetected. Mutation profiling increased clinician confidence in management recommendations and resulted in more conservative management in 10% of patients. Mutation profiling increased the rate of benign disease in patients recommended for conservative management (84% to 92%, p<0.05) and the rate of malignant disease in patients recommended for aggressive treatment (53% to 71%, p<0.05). Discussion Mutation profiling improved diagnostic accuracy and significantly impacted management decisions. Low risk mutation profiling results increased recommendations for conservative management and increased the rate of benign outcomes those patients, helping to avoid unnecessary aggressive interventions and improve patient outcomes.