June 10, 2025
Cholangiocarcinoma is a rare and difficult-to-treat cancer of the bile duct. Its silent presentation often results in delayed diagnosis and a poor outlook.
Surgery and liver transplant have the potential to cure the disease. However, less than half of patients are eligible for surgery, and only a fraction qualifies for transplant. Even when these procedures are possible, they are complex and risky.
The overall five-year survival rate for cholangiocarcinoma is less than 10%, but there are glimmers of hope, says Rory L. Smoot, M.D., a hepatobiliary and pancreas surgeon at Mayo Clinic Comprehensive Cancer Center in Rochester, Minnesota.
"If we can establish clear margins with resection and the lymph nodes are not involved, the median survival is around 4 to 5 years. These patients have a 20% to 30% chance of a cure," says Dr. Smoot. "I tell patients we'll strive for a cure. But even if we can't get that, we may be able to prolong survival for new therapies to come along."
Reaching an optimal treatment path with a multidisciplinary team
Cholangiocarcinoma care begins with an evaluation by a multidisciplinary team. Mayo Clinic team members work together to review cases as a tumor board.
During team discussions, the team considers all treatment options. Hepatobiliary and transplant surgeons determine whether the patient is a candidate for surgery or liver transplant. Endoscopists, interventional radiologists, medical oncologists and radiation oncologists review adjuvant therapies that can increase the success of surgery.
Determining the right surgical approach depends on a wide range of factors, for example, if a patient has distal cholangiocarcinoma and primary sclerosing cholangitis (PSC). "Our initial thought might be to consider a Whipple procedure," says Dr. Smoot. "Given the known risk of disease involving multiple areas of the bile duct in patients with PSC, we typically perform diagnostic brushings of the entire biliary tract. If the results suggest multiple areas of tumor development in the liver, resection alone would not be able to remove all the disease."
In this scenario, the patient might then be evaluated for a transplant plus a Whipple procedure — an operation available in only a few centers nationwide.
Preoperative strategies to improve the safety of cholangiocarcinoma surgery
Achieving better surgical outcomes starts before surgery. Many patients with cholangiocarcinoma require stents to open bile ducts and improve liver function. Surgeons also need to ensure there are no signs of infection, which can cause liver failure after surgery.
Another critical aspect of preoperative care is the timing of surgery with respect to other therapies since many patients receive neoadjuvant chemotherapy to reduce tumor size. Systemic therapies also can be used when surgery isn't possible and after surgery.
When determining whether surgery is an option for cholangiocarcinoma, the most important considerations include:
- Absence of metastatic disease.
- Patient is medically able to undergo a major operation.
- Surgeon has a viable approach based on a review of the imaging.
It's also critical for team members to be able to recognize and manage complications so they don't become life-threatening. "Despite the complexity and danger of cholangiocarcinoma surgery, most of our patients don't spend any time in the intensive care unit," says Dr. Smoot. "This reduced need for ICU care is just one benefit of having surgery at a high-volume center."
Liver transplant protocols for cholangiocarcinoma
The protocol for liver transplant in patients with early-stage perihilar cholangiocarcinoma was developed in 1993 at Mayo Clinic in Rochester, Minnesota. Patients must meet strict criteria to be eligible and undergo additional therapies, such as chemotherapy and radiation, as part of the treatment protocol.
Some patients who come to Mayo Clinic looking for a transplant are disqualified due to a prior procedure. If a patient might be a candidate for transplant, Dr. Smoot recommends avoiding:
- Attempt at resection.
- Metal stent placement (plastic stents are acceptable).
- Percutaneous needle biopsy (for patients with perihilar cholangiocarcinoma).
Developing novel systemic therapies for cholangiocarcinoma
Systemic therapies are on the leading edge of cholangiocarcinoma care. "Our team works with referring providers so patients can get approved treatments close to home," says Dr. Smoot.
Although Dr. Smoot is a surgeon, his research focuses on finding new drugs for cholangiocarcinoma. "I do this work because the overall outlook for this cancer is unlikely to improve with surgery alone," he says. "I also see a need to find targets for all the different mutations that occur — even within a single tumor."
Mayo Clinic continues to support cholangiocarcinoma research and open clinical trials to make new treatments available to patients who need them.
For more information
A collaborative approach using liver transplant for perihilar cholangiocarcinoma treatment. Mayo Clinic; 2025.
Treating early stage bile duct cancer with chemoradiation, liver transplant. Mayo Clinic; 2022.
Refer a patient to Mayo Clinic.