Next-generation sequencing improves the detection of malignant biliary strictures and changes management

Background and Aims: Malignant biliary strictures (MBSs) pose diagnostic and therapeutic challenges due to the frequent indeterminate results after initial sampling. A next-generation sequencing (NGS) panel (BiliSeq) offers promise in MBS detection, but real-world performance remains uncertain. This study aimed to assess standard sampling techniques alone and with BiliSeq for malignancy detection in biliary strictures and to evaluate management changes based on NGS. Methods: This retrospective cohort study included 77 patients with biliary strictures undergoing BiliSeq during ERCP. Sensitivity, specificity, positive predictive values, and negative predictive values were calculated, and sensitivity was compared between tests by using the McNemar test. Clinical impact was defined by identifying MBS patients with negative cytology/pathology correctly identified by BiliSeq. Results: Among 77 patients (28 malignant, 49 benign) who underwent BiliSeq testing during ERCP, primary sclerosing cholangitis was present in 24 patients (31.2%). A mass was detected in 35.7% of MBS cases versus 6.1% of benign cases (P = .001). BiliSeq sensitivity for malignancy was 75% (95% CI, 55.1%-89.3%), surpassing the combination of cytology and biopsy (42.9%; 95% CI, 24.5%-62.8%; P = .03). Combining BiliSeq with cytology/biopsy improved sensitivity from 42.9% to 85.7% (P < .001). Among MBS patients with negative cytology/biopsy findings (n = 16), BiliSeq altered management in 75%. Conclusions: NGS and pathologic evaluation enhanced MBS detection sensitivity, leading to management changes in 75% of cases when pathology test results were negative.