A newly developed molecular test called BiliSeq detects bile duct cancer with about twice the sensitivity of conventional pathological findings. This is shown by the results of a large, six-year study involving more than 2,000 patients and nearly 3,000 bile duct samples, which was published today in the journal Gastroenterology.
Bile duct cancer (cholangiocarcinoma) is rare but aggressive. Strictures or blockages of the bile ducts present a major diagnostic challenge for physicians because conventional biopsies and cytological examinations often lead to false-negative results – especially when tumors are small, difficult to access, or surrounded by inflammation and scar tissue.
BiliSeq uses next-generation sequencing (NGS) to detect cancer-associated genetic mutations in bile duct tissue. The test works even when only a few or damaged tumor cells are present under the microscope. In the prospective, multicenter study, BiliSeq alone detected about 82 percent of bile duct cancers, compared to only 44 percent with standard pathology. The combination of BiliSeq and pathology increased the detection rate to almost 90 percent, while maintaining very high specificity (benign changes were rarely misclassified as malignant).
The test is particularly valuable in high-risk groups such as patients with primary sclerosing cholangitis (PSC) or Hispanic patients, where pathology alone can miss up to half of cancers. In combination with BiliSeq, the detection rate here increased to up to 86 percent.
In addition to cancer diagnosis alone, BiliSeq provides additional treatment-relevant genetic information for about one in five patients. In almost a third of these cases, the results led to a change in therapy management – for example, in the decision about a liver transplant. "This is where diagnostics truly becomes personalized medicine," said study author Prof. Dr. Adam Slivka of the University of Pittsburgh School of Medicine.
The study, titled "DNA/RNA-Based Next-Generation Sequencing (NGS) Improves the Early Diagnosis and Management of Neoplastic Bile Duct Strictures: A Six-Year, Prospective, Multi-Institutional, Real-Time Study," was conducted by researchers from UPMC Hillman Cancer Center and the University of Pittsburgh and funded in part by the National Institutes of Health.
BiliSeq is not a screening test for the general population, but is used specifically in patients with unclear bile duct strictures. The authors hope that the test will lead to fewer repeat examinations, shorter waiting times, and better treatment options for those affected in the future.
