Yield of next-generation sequencing in diagnostic work up of suspicious biliary strictures

This study addressed the need for improved diagnostic tools to identify malignancy in suspicious biliary strictures. Traditional cytological morphology is often indecisive, prompting exploration of next-generation sequencing (NGS) for enhanced sensitivity. Our aim was to evaluate NGS's additional value in classifying biliary brushes and biopsies and its impact on clinical decision making (CDM).

In this retrospective single-center cohort study, patients were included from 2019 to 2022 in whom morphologic interpretation and NGS were performed on cytological or histological material from suspicious biliary strictures. Sensitivity and specificity of NGS were calculated for benign or atypical vs. suspicious for malignancy or malignant morphology in biliary brushes and biopsies. In addition, changes in CDM after NGS outcome were evaluated.

In total 109 samples from 106 patients were included in the study. NGS correctly identified 42 of 75 malignancies (56%). Sensitivity and specificity of morphology for brushes were 56% (95% confidence interval [CI] 43%-68%) and 94% (95% CI 79%-99%), respectively. Adding NGS resulted in sensitivity and specificity of 78% (95% CI 66%-87%) and 94% (95% CI 79%-99%). For biopsies, sensitivity and specificity of morphology were 67% (95% CI 35%-90%) and 67% (95% CI 9%-99%) and adding NGS did not alter these results. The outcome of NGS resulted in a change of classification of morphology in 36% and a change in CDM in 8%.

NGS in brushes contributed to more accurate/sensitive diagnoses of malignancy than morphology alone. There was a limited impact on CDM change, but in the future, NGS will undoubtedly play a bigger role when targeted therapy is incorporated in standard treatment and more sensitive NGS panels for cholangiocarcinoma are developed.