UCLA’s Liver Transplant Program continues to see highly encouraging results through a protocol involving a combination of neoadjuvant chemotherapy and radiation followed by transplantation for patients with cholangiocarcinoma, or bile-duct cancer. The program has approximately 13 years of experience with the approach and remains one of only a few centers in the United States with a protocol for liver transplantation of patients with the otherwise lethal cancer — and among the only sites offering liver transplantation for intrahepatic cholangiocarcinoma, which occurs in the bile ducts within the liver.
“Cholangiocarcinoma is an insidious cancer that often affects patients in the prime of their lives,” says Sammy Saab, MD, MPH, chief of transplant hepatology and medical director of the UCLA Adult Liver Transplant Program. “It tends to develop without symptoms, and there are no standardized ways of screening for people at risk, so it’s often diagnosed very late in the disease course. Many physicians in the community have considered this to be a death sentence, but the therapy provided by the multidisciplinary team at UCLA has been a game changer, and we want referring physicians to know that there is an opportunity to improve these patients’ quality of life and survival.”
Fady Kaldas, MD, associate professor of surgery and director of the UCLA Liver Transplant Service, notes that historically, liver transplantation of cholangiocarcinoma patients has been associated with high rates of recurrence and overall outcomes so poor that they didn’t support doing the operation. That changed at UCLA with a comprehensive approach involving multidisciplinary care in which patients receive radiation therapy and chemotherapy prior to the transplant. This includes patients with intrahepatic cholangiocarcinoma as well as those with hilar cholangiocarcinoma, in which the tumor is in the bile ducts just outside the liver.
In September, the team led by Dr. Kaldas published in Liver Transplantation “A Three Decade Single Center Experience of Liver Transplantation for Cholangiocarcinoma; Impact of Era, Tumor Size, Location and Neoadjuvant Therapy,” covering UCLA’s experience with more than 50 intrahepatic and hilar cholangiocarcinoma patients who received transplants both before and after the current protocol was initiated. The results were striking — including a 100% survival in patients with intrahepatic cholangiocarcinoma treated with neoadjuvant chemo-radiotherapy followed by transplantation.
“We’ve learned that if patients are able to respond to chemo-radiotherapy before transplant, their outcomes are significantly better, certainly justifying the operation,” Dr. Kaldas says. “In fact, we have found that the tumor size is less relevant than previously suspected. If the patients are able to tolerate either chemotherapy or radiation — ideally both — and then get a liver transplant between six months and a little over a year after diagnosis, they tend to have the best outcomes. Obviously, this is a much less common cancer than hepatocellular carcinoma, so the numbers are small. But the outcomes continue to improve across the board.”
Drs. Saab and Kaldas believe a key to the protocol’s success is the comprehensive, multidisciplinary nature of the care, which involves experts in hepatology, medical oncology and radiation oncology working together in managing patients and tailoring treatment to their individual case — including not just transplantation but liver resections where appropriate. One of the challenges the UCLA team has faced is ensuring that cholangiocarcinoma patients can get a liver once listed for transplant. “Access for these patients tends to be limited because their liver continues to work, despite it having this terrible cancer in it, and within the transplant community most centers aren’t doing liver transplants for cholangiocarcinoma — or if they are, it’s with extremely rigid criteria,” Dr. Kaldas says. “We hope our experience will support moving these patients up on the list.”
The UCLA liver-transplant team also hopes to get the word out to physicians in the community that early referral of cholangiocarcinoma patients can save lives. “Unfortunately, many of these patients show no other liver disease when they get this problem, so we are advocating having a low threshold of suspicion before imaging patients and studying them if there is any concern, especially for high-risk patients — those with primary sclerosing cholangitis, for example, and those with a family history,” Dr. Kaldas explains. “We also need to change the thinking that there is no hope for these patients once diagnosed unless they have a small lesion that can be easily resected. We have incredible cases of survival involving patients who would have been considered untransplantable under protocols followed by most centers. Hearing from such patients who, years later, are living normal lives is what motivates us to continue doing what we do.”
“A Three Decade Single Center Experience of Liver Transplantation for Cholangiocarcinoma; Impact of Era, Tumor Size, Location and Neoadjuvant Therapy,” Liver Transplantation, September 5, 2021.