Researchers at the University of Pittsburgh have developed a next-generation sequencing (NGS) test that can significantly improve the accuracy of bile duct cancer diagnoses. In a study published today in the Gastroenterology journal, the molecular test correctly detected bile duct cancer in 82% of patients compared to 44% when using conventional pathology-based diagnostics.
Bile duct cancer remains difficult to detect in the early stages, since symptoms can be similar to those of other conditions and the tumors are small and located deep within the body. In patients with narrowing or blockage of the bile ducts, cancer can often be indistinguishable from inflammation and scarring surrounding the tissue, leading traditional diagnostics to often produce false negative results.
“For decades in bile duct cancer we’ve known that a negative biopsy doesn’t always rule out cancer,” said Adam Slivka, MD, PhD, professor of medicine in the division of gastroenterology, hepatology, and nutrition at Pitt School of Medicine. “That uncertainty drives repeat testing and sometimes surgery without clear answers.”
To overcome this challenge, Slivka and colleagues developed an NGS test that detects both DNA and RNA in a biopsy sample to determine whether a malignant tumor is present. Named BiliSeq, the test looks at hundreds of cancer-associated genes and fusion genes to improve detection rates of bile duct cancer.
In the current study, BiliSeq was used to evaluate over 2,800 samples from more than 2,000 patients across 28 medical institutions who were scheduled to undergo a bile duct biopsy. The molecular test achieved 82% sensitivity when diagnosing bile duct cancer, whereas standard pathology methods only reached 44%. When combining both pathology and NGS testing, sensitivity was increased to 88% while maintaining high specificity.
In 20% of patients with positive results, BiliSeq was also able to identify actionable molecular alterations. In 30% of these cases, these results led physicians to modify the treatment course.
“That’s where this really becomes personalized medicine,” said Slivka. “For these patients, BiliSeq means less testing, less waiting, and more options.”
Importantly, the test also showed a significant increase in bile duct cancer detection rates among patients belonging to high-risk populations. These included Hispanic patients, who are 50% more likely to develop bile duct cancer, as well as individuals carrying genetic mutations linked to a higher cancer risk and patients with primary sclerosing cholangitis (PSC).
Among these groups, the largest effect was seen in PSC patients, for whom cancer can be particularly difficult to distinguish from inflamed tissue. In this high-risk group, BiliSeq increased sensitivity from 26% to 85%.
“Treating these patients was my biggest motivation,” said Slivka. “Seeing young patients with PSC develop bile duct cancer and die underscored the need for a better way to identify cancer earlier in the diagnostic process or detect high-risk genetic changes when standard testing falls short.”
At the University of Pittsburgh Medical Center, patients whose cancers are diagnosed using BiliSeq may be eligible for a living-donor liver transplant program, which can significantly shorten the wait time to access a life-saving transplant. “This diagnostic test has become invaluable in our novel transplant program for patients with early-stage bile duct cancer,” said Slivka. “Time is always critical when dealing with lethal cancers.”
