LA JOLLA, CALIF. — Improvements in the short- and long-term survival of hepatocellular carcinoma patients are being realized through liver transplantation, surgical resection, and several new therapies, Dr. Donald J. Hillebrand said at a meeting on chronic liver disease sponsored by Scripps Clinic.
Even so, the incidence of hepatocellular carcinoma (HCC) has increased from 1.4 per 100,000 patients in the mid-1970s to 3.3 per 100,000 in 2000–2002. “This disease is on the rise, which is in contrast to most of the abdominal cancers that we deal with on a day-to-day basis,” said Dr. Hillebrand, medical director of liver transplantation for the Scripps Center for Organ and Cell Transplantation in La Jolla, Calif.
At the same time, the prognosis for patients with HCC remains dismal. An estimated 90% of all patients with the diagnosis succumb to the disease. “Roughly half of these patients will die of the tumor,” he said. “The other half will die from progression of their liver disease. So the more aggressive we are with therapy, the more we push them, but the closer we are to helping them achieve locoregional control.”
Dr. Hillebrand emphasized the need for a multidisciplinary approach to HCC. “It can't be just a liver transplant program, because many individuals will benefit from resection,” he said. “The hallmark in the middle of all this is the role of the hepatologist. I probably see more HCC than our oncologists, because they come to us in the liver clinic. In general we don't send an individual to an oncologist unless we've exhausted all of the other locoregional treatment options.”
The best prognostic group includes patients with a performance status of zero and no constitutional symptoms, Child-Pugh class A cirrhosis, no vascular invasion, and no extrahepatic spread.
Liver transplant “by far achieves the best outcome in patients with decompensated cirrhosis who meet criteria,” Dr. Hillebrand said. “Unfortunately, there is a shortage of organ donors available. We can't transplant everybody with HCC.”
Surgical resection can be effective in patients without cirrhosis if there is no vascular involvement, because they don't have portal hypertension or hepatic insufficiency. Resection can also be effective in patients with cirrhosis and preserved liver function and relatively early-stage liver cancer. Patients with Child-Pugh class A cirrhosis who have a peripherally located single lesion “can do quite well, with 60% long-term survival,” he said.
Dr. Hillebrand noted that candidates for surgical resection should be stratified based on their ability to survive the procedure. “So if the patient has clinically significant portal hypertension or increased serum bilirubin, those are two hallmarks against the ability to tolerate resection,” he said.
Indications for surgical resection in patients with no cirrhosis include tumors of any size, as long as there is no microvascular, lymph node, or extrahepatic spread, and resection is technically feasible.
Indications for surgical resection in patients with cirrhosis include having Child-Pugh class A disease, no clinically significant portal hypertension, and a bilirubin level of less than 1 mg/dL. With these criteria, “probably no more than 5% of the HCC that we see in the Western world would be eligible for resection,” he said.
Some transplant surgeons are performing portal vein embolization ipsilateral to the tumor to promote hypertrophy of the contralateral lobe. Although this procedure is rare, “there are some data that suggest this may improve the resectability of these tumors,” Dr. Hillebrand said. “Usually it's done at major centers that have a tremendous experience with hepatic resection and are more willing to push the envelope.”
He pointed out that 50%–75% of patients who undergo surgical resection for HCC will develop a local recurrence or a second primary tumor.
Dr. Hillebrand went on to highlight the following new therapies for HCC:
▸ Ablative therapies. These include chemically mediated forms, such as percutaneous ethanol injection and acetic acid injection, as well as energy-mediated forms, such as cryoablation, microwave ablation, and radiofrequency ablation.
Ablative therapies “can serve as a bridge to transplant,” while avoiding upper abdominal scarring. They “provide effective control of the tumor for up to 1–2 years while patients wait for a liver transplant,” Dr. Hillebrand said. “For select patients, ablation may offer the same 5-year survival results as surgical resection. The question that hasn't fully been answered yet is, is there initial benefit to tumor reduction, the so-called concept of downstaging?”
▸ Locoregional therapies. These include transarterial chemoembolization, radioactive yttrium-impregnated class microspheres, targeted radiation therapies, laser beam therapies, and cisplatinum gel injection.
One phase II trial of proton beam therapy in 34 patients with HCC and an average tumor size of 5.7 cm demonstrated a 75% local tumor control rate at 2 years (Gastroenterology 2004;127:S189–93).