UF researchers find transplantation effective for some liver cancer patients

Researchers from the University of Florida and the University of Toronto have found that liver transplantation appears to be a viable alternative for some patients with liver cancer, a group that historically has had few options.

Such patients have rarely received transplants because surgeons believed their prognosis was poor, but a new study suggests the treatment gives certain liver cancer patients a survival rate comparable to that of those who receive liver transplants for other liver diseases. At a time when liver cancer rates are set to skyrocket, UF and Toronto surgeons have more clearly defined which patients might actually benefit.

Interestingly, researchers found that tumor size or the number of tumors had no effect on how well patients fared after transplant. Instead, patients were likely to do well unless tumors had invaded blood vessels within the liver. Researchers reported their findings in the May issue of the Annals of Surgery.

“The good news is many people with tumors may be able to undergo transplantation very successfully, with about a 60 percent five-year survival overall,” said Dr. Alan W. Hemming, an assistant professor of surgery at UF’s College of Medicine and the UF Shands Cancer Center.

“That’s a cure rate that is better than surgically removing tumors and as good as results for anyone else we’re transplanting. In the more recent era that means that most people who receive transplants for primary liver cancer aren’t dying of tumors – they’re just dying of whatever else we all die of.”

Experts expect the number of patients diagnosed with liver cancer to soar in the next decade. That’s due to the increasing incidence of hepatitis C, a virus that permanently scars the liver and paves the way for the development of malignancies years after infection. More than 170 million people worldwide are infected with hepatitis C, which can silently attack the liver for decades before routine medical tests discover the damage. Up to half will develop cancer.

Hepatitis C, considered the most serious of the five viruses in the hepatitis family, typically causes chronic inflammation of the liver, leading to scarring, liver cancer or liver failure. The disease is the most common reason liver transplants are conducted in the United States, independent of its association with liver cancer.

“If you think of hepatitis C going through the population back in the mid-‘70s, predominantly due to intravenous drug use and, in some cases, blood transfusions, we’re just getting to the point where we’re starting to see all of the tumors,” Hemming said. “One mathematical model estimated that by the year 2010 the total number of tumor patients who could be treated by transplantation would exceed the number of donor livers currently available. Cancer patients alone could take up all the organs, never mind the rest of the folks who need a transplant to treat other diseases. That’s why it’s an important issue to come to grips with now.”

The new findings suggest surgeons need to reassess how patients are evaluated for transplantation, he said.

“A substantial number of practitioners out there might just write these patients off,” he said. “A lot of people think that if someone has cirrhosis and a primary liver tumor there’s no curative therapy for them. But transplantation should definitely be kept as an option, and transplant centers should see these patients.”

Historically, liver transplantation was attempted in patients with very large liver tumors. The results were dismal: Almost everybody suffered a recurrence in the first two or three years after the operation and then died, Hemming said. That led to a sharp decline in the number of transplants for these patients. While the UF/Toronto study found tumor size, when combined with other factors, did not appear to influence outcome, patients with large tumors may not have fared well years ago because tumor size is likely linked to a higher probability that the growths will have invaded nearby vessels.

Researchers studied 112 men and women ages 11 to 58 with a form of liver cancer known as hepatocellular carcinoma. All underwent a liver transplant between 1985 and 2000, half through the Shands Transplant Center at UF and half at Toronto Hospital.

Each year, hepatocellular liver cancer accounts for more than 1 million deaths worldwide. Without treatment, patients typically only survive six to nine months. Standard therapy is to surgically remove cancerous growths, but often they return with a vengeance. Some are unable to undergo standard surgery because of poor liver function, and the number of tumors or their location. Radiation and chemotherapy, meanwhile, are generally ineffective.

“Transplantation, in theory, is an ideal therapy, because by taking out the whole liver you not only remove the tumor with the widest possible surgical margin but also fix the underlying liver disease, ending up with a healthy, functioning liver,” Hemming said.

Seventy-eight percent of the study participants survived a year after the transplant, while 63 percent were alive three years after surgery and 57 percent five years after the operation – a survival rate comparable to that noted for patients who received liver transplants for other reasons. Those with the worst outcomes had tumors that invaded blood vessels within the liver. The rate of tumor recurrence at five years was 65 percent in these patients, compared with only 4 percent for those whose tumors had not infiltrated the vessels.

Unfortunately, a shortage of donors means there aren’t enough organs for everyone, Hemming said. Each year, more than 1,700 patients die awaiting a transplant, according to the United Network for Organ Sharing. Due to the scarcity of organs, current practice is to opt for standard surgery to remove the tumors, if a patient’s liver function is normal.

“(These findings) could indeed change our practice, specifically with respect to advocating live-donor liver transplantation for patients with larger tumors,” said Dr. Andrew S. Klein, chief of the division of transplantation at The Johns Hopkins University School of Medicine. “Although cadaveric organ donation rates have remained relatively static, a growing number of transplant programs...have developed the capacity to perform liver transplants utilizing a portion of the liver removed from a healthy volunteer donor.”