When patients develop a narrowing or blockage in the bile ducts, physicians must determine whether the cause is cancer or a benign condition. The location of these blockages adds challenges to the diagnosis, and this uncertainty can delay treatment decisions for patients in the event they have this rare type of cancer.
A team of researchers has developed BiliSeq, a molecular test that, according to recent research, detected bile duct cancer with twice the sensitivity of the standard test, giving physicians a more accurate picture of the patient’s diagnosis.
Findings published by Das et al in Gastroenterology describe the evaluation of BiliSeq’s real-world performance over 6 years in more than 2,000 patients across the United States, analyzing nearly 3,000 bile duct specimens. BiliSeq detected approximately 82% of bile duct cancers compared to 44% with pathology alone. More importantly, when combined with pathology, BiliSeq increased cancer detection to nearly 90%—while rarely misclassifying benign disease as malignant.
Because bile duct tumors are often small, difficult to reach, and surrounded by inflammation or scar tissue, standard biopsy and cytology methods often fail to give doctors a clear diagnosis.
“For decades, in bile duct cancer, we’ve known that a negative biopsy doesn’t always rule out cancer,” said co-corresponding author Adam Slivka, MD, PhD, Professor of Medicine (Division of Gastroenterology, Hepatology, and Nutrition) at the University of Pittsburgh. “That uncertainty drives repeat testing and sometimes surgery without clear answers.”
BiliSeq addresses this limitation by detecting genetic mutations associated with cancer in bile duct tissue. The test functions even when tumor cells are sparse, damaged, or indistinguishable from inflammation under the microscope—a key limitation of traditional pathology, which can miss cancers and produce false-negative results.
BiliSeq is not a screening test for the general population. Instead, it is used for patients with bile duct narrowing or obstructions that need a clearer diagnosis.
One of the most important advantages of the test is that it provides more than a simple yes-or-no answer to patients waiting for a diagnosis. In the study, BiliSeq identified treatment-relevant genetic information in about one out of every five patients. In nearly one-third of those cases, that information led doctors to change how care was managed.
“That’s where this really becomes personalized medicine,” added Dr. Slivka, who also directs the gastroenterology service line at the University of Pittsburgh Medical Center (UPMC).
BiliSeq results are already being used alongside standard clinical evaluation to help inform liver transplant decision-making in select patients at UPMC.
The study also reported on BiliSeq’s detection performance across high-risk patient groups, including patients with primary sclerosing cholangitis and Hispanic patients. In these populations, pathology alone could miss up to half of cancers. However, when combined with BiliSeq, clinicians were able to identify up to 86% of cancer cases.
The large, prospective, multi-institutional design makes the findings representative of real-world clinical practice. “We receive and analyze samples from patients at medical centers across the country,” Dr. Slivka said. “For these patients, BiliSeq means less testing, less waiting, and more options.”
DISCLOSURE: This study was supported in part by the National Institutes of Health, Western PA Chapter-National Pancreas Foundation, the Sky Foundation, and the Pancreatic Cancer Action Network. For full disclosures of the study authors, visit gastrojournal.org.
