Combining radiation, chemotherapy and liver transplantation increases survival in bile duct cancer patients

A new treatment for patients with a type of bile duct cancer promises a greater chance at survival by combining radiation, chemotherapy and liver transplantation, Mayo Clinic physicians report in the September issue of the Annals of Surgery.

The five-year survival rate for patients who received a liver transplant after radiation and chemotherapy was 82 percent, significantly higher than for those who had a conventional operation. "With the combined benefits of radiation, chemotherapy and liver transplantation, our patients with bile duct cancer now have a much better chance to live longer and enjoy a good quality of life," says Charles Rosen, M.D., a Mayo Clinic transplant surgeon and co-author of the study.

Conventional therapy for hilar cholangiocarcinoma, a type of bile duct cancer, is to remove (resect) the tumor, which may require removing part of the liver. Survival for patients with this type of operation is only 25 to 35 percent, and many patients cannot be treated this way because the tumors can involve both sides of the liver. Combination therapy with liver transplantation is possible for more patients. Transplantation enables surgeons to remove the entire liver and obtain better tumor clearance. Patients treated with transplantation have enjoyed a higher likelihood of prolonged survival than those treated with the conventional operation.

To improve results of liver transplantation for unresectable hilar cholangiocarcinoma, Mayo Clinic physicians developed a treatment protocol combining radiation therapy, chemotherapy and liver transplantation. Patients receive high dose external beam radiation therapy, followed by high dose irradiation with iridium administered through a catheter passing through the bile duct and tumor. Chemotherapy starts during radiation treatment and continues until transplantation. Prior to transplantation, patients undergo a staging abdominal operation so surgeons can look for any spread of the tumor to lymph nodes or the abdomen that would prevent complete tumor removal.

Mayo Clinic's liver transplant team has treated over 90 patients with hilar cholangiocarcinoma. Approximately one-third of the patients have findings at the staging operation that preclude subsequent transplantation, but this number may be decreasing with earlier diagnosis and referral for treatment. Sixty patients have undergone liver transplantation -- many recently with living donors -- and results remain superb, says Dr. Rosen.

Cholangiocarcinoma is a relatively uncommon malignant tumor that is often found in the lining of the bile duct. In the United States, the most common risk factor is sclerosing cholangitis, a chronic liver disease characterized by inflammation, destruction and fibrosis of the bile ducts, often leading to cirrhosis of the liver. The cancer also is seen in patients with congenital bile duct cysts and bile duct stones. Most frequently, these tumors are located near the liver. Cholangiocarcinomas in this location are difficult to treat because the tumor often extends deep into the liver in a way that it cannot be completely removed with a conventional operation.

The incidence of bile duct cancer is increasing in the United States, according to Gregory Gores, M.D., Mayo Clinic liver transplant specialist and co-author of the study. Mayo Clinic has ongoing research into new tests to diagnose the tumor earlier, which could lead to even better results.

"The major problem is that we still don't have enough livers for everyone who needs one," says Dr. Rosen. "We feel that patients with cholangiocarcinoma should have equal access to donor organs, because the results are comparable to those achieved for other patients who undergo transplantation. Without a transplant, the outlook for these patients is fairly poor."

Other Mayo Clinic physician researchers involved with this study include: David Rea, M.D., Julie Heimbach, M.D., Michael Haddock, M.D., Steven Alberts, M.D., Walter Kremers, Ph.D., and David Nagorney, M.D.