Immunotherapy and precision medicine are offering new hope against one of the most challenging cancers.

Cholangiocarcinoma, or bile duct cancer, is one of the most difficult cancers to diagnose and treat.

This rare and aggressive malignancy typically doesn’t cause noticeable symptoms until more advanced stages. The American Cancer Society says the average five-year survival is about 10%, depending on the size of the tumor and whether the cancer has spread.

However, for the first time in more than a decade, new treatment innovations are demonstrating potential to improve patient outcomes and survival.

Why is cholangiocarcinoma hard to detect and treat?

Cholangiocarcinoma affects the biliary system and the digestive system. It forms in the tubes that carry bile from the liver and gallbladder to the small intestine.

“It’s an area of the body where it’s very inaccessible, with two separate organ systems that are completely intertwined,” says Robert Selby, MD, a hepatobiliary and pancreatic surgeon with the USC Hepatobiliary Surgery Program, part of Keck Medicine of USC. Selby also specializes in liver transplants at Keck Medicine’s USC Transplant Institute.

“You’ve got a convergence of artery, vein and bile duct in a tiny nook, and they’re all very close to each other,” he continues. “The bile duct apparatus is not easy to image or operate on, and tumors don’t need to be very big to impact the surrounding vessels.”

Due to a lack of known biomarkers, there isn’t currently a way to screen patients and detect bile duct cancer early, Selby adds. Due to the lack of screening options, bile duct cancer is often more locally advanced or has metastasized by the time it’s detected.

When is surgery a viable option for cholangiocarcinoma?

Removing the tumor can lead to a potential cure for cholangiocarcinoma. Throughout the 1990s and 2000s, surgical resection followed by chemotherapy provided the best chance for longer-term survival, although disease recurrence remains high.

Only about 20%-30% of patients are even eligible for surgical resection, however. The tumor’s location, poor liver function and metastasized disease can make resection impossible or too dangerous.

One promising surgical advancement has been liver transplantation. Studies show that living donor transplants can significantly extend survival rates.

However, less than 5% of patients qualify for a liver transplant. To be eligible for liver transplant, the tumor must be unresectable and small, and the cancer must be non-metastasized and localized to the liver.

Selby says he has successfully performed transplants on patients with perihilar cholangiocarcinoma. He theorizes that as medical therapies continue to improve, and if these treatments can successfully shrink bile duct tumors, then liver transplantation could be a viable option for more patients in the future.

How are systemic therapies improving?

In the 2010s, the combination of two chemotherapy drugs (gemcitabine and cisplatin) became a standard treatment for cholangiocarcinoma and extended average survival rates.

Today, advancements in immunotherapy are shifting treatment approaches. The standard first-line treatment for advanced or metastatic bile duct cancer is now a combination of chemotherapy and immunotherapy.

“I think it’ll probably be immunotherapy that allows for downstaging or even cure,” Selby says.

Immune checkpoint inhibitors are among the most common forms of immunotherapy used for bile duct cancer. These lab-made proteins ensure the immune system’s T cells continue to fight and kill cancer cells. Research shows adding immune checkpoint inhibitors can increase survival more than chemotherapy alone.

Precision medicine is also leading to promising advancements. With molecular profiling, physician-scientists can identify genetic mutations on tumor tissue and then use that information to more precisely target the cancer.

Selby says these therapies could be especially beneficial for patients with inoperable tumors. “I suspect the advancement would really be for patients who have more extensive local disease and trying to downstage it to where they only have minimal local disease.”

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