New options for patients with bile duct cancer

Hilar cholangiocarcinoma, which affects 2,000 to 3,000 Americans each year, is notoriously difficult to treat. Surgical resection, once the only potentially curative approach, is technically challenging and results have generally been disappointing.

But since the late 1990s, Mayo Clinic has had remarkable success treating bile duct cancer with liver transplantation using a protocolized approach and strict selection criteria.

"Mayo has taken the world lead in creating a protocol for liver transplantation for bile duct cancer," says Denise M. Harnois, D.O., of Mayo Clinic in Florida. "Although a few centers reported excellent results using our program, the generalizability of the results had never been established. There is always some concern that a protocol may not be as effective when applied universally."

To investigate the efficacy of the Mayo Clinic treatment in institutions with varying neoadjuvant protocols, Dr. Harnois and colleagues invited large-volume transplant centers across the United States to take part in a multicenter study.

"Twelve institutions met our criteria of having a UNOS-approved protocol for neoadjuvant therapy and experience transplanting at least three patients with hilar cholangiocarcinoma from 1993 to 2010," Dr. Harnois explains.

In all, 287 patients participated. The median age was 59 years, the majority of patients were male and more than half had primary sclerosing cholangitis.

The Mayo Clinic protocol

"Primary sclerosing cholangitis is the main risk factor for hilar cholangiocarcinoma, and unfortunately, in many of these patients, the cancer has spread," Dr. Harnois says. "Our protocol is targeted at a select group of patients without extrahepatic disease, including regional nodal metastasis, and a single lesion of 1.18 inches (3 centimeters) or less."

The selection criteria also exclude people who have previously undergone treatment — chemotherapy, radiotherapy, operative biopsy or resection — have been diagnosed with cancer other than skin cancer in the past five years, or have a comorbid condition or uncontrolled infection.

Methods and results

Patients in the current study underwent exploratory laparotomy to check for metastases before entering the transplant treatment protocol. All 287 then completed various combinations of neoadjuvant therapy, including external radiation, brachytherapy and chemotherapy boost.

Ultimately, 71 patients did not undergo liver transplantation due to disease progression, death or treatment intolerance. For those who did, recurrence-free rates at two and five years were 79 percent and 66 percent, respectively, with no difference between people treated at Mayo Clinic in Rochester, which had the largest number of patients, and those treated at other centers.

Patients treated outside UNOS selection criteria had significantly worse five-year recurrence-free rates.


"This study confirms that a combination of neoadjuvant therapy and liver transplantation leads to excellent outcomes, despite differing protocols," Dr. Harnois says. "It's encouraging that that the program can be successful outside Mayo Clinic."

She adds, "Before our protocol was widely accepted, it was difficult to list patients for this procedure. But because of its success, regional review boards have agreed that patients who follow the Mayo protocol and meet the criteria will automatically be granted exception points. So we can now offer options to people who otherwise would have none."

Dr. Harnois says that problems with organ availability can often be overcome with living related transplants, noting that many patients at Mayo Clinic in Rochester receive such transplants.

But despite the success of the protocol at Mayo Clinic and elsewhere, Dr. Harnois cautions that it isn't appropriate for all institutions.

"A large, established transplantation program is critical to protocol success," she says. "It requires a strong team that not only includes the medical hepatologist and transplant surgeon but also extends to oncology, radiation oncology and nutrition. Not all centers can develop that expertise. And strict patient criteria are critical."

Dr. Harnois says that she and her colleagues in Florida continue to work with the oncology team to develop protocols for patients who don't qualify for transplantation.

"We're working on innovative approaches that we hope will offer options to every patient. Most involve new chemotherapy agents. We're currently treating a patient in his 20s with systemic chemotherapy, and he's doing very well."