Liver Transplant Ups Survival in Hepatocellular Carcinoma

SAN FRANCISCO—Liver transplantation is lifesaving in patients with localized hepatocellular carcinoma, with some 75% of transplant recipients still alive 5 years later, compared with only 12% of other patients, finds the first large population-based study of this treatment for this disease. However, African-American, Hispanic, and Asian patients are only about half as likely to undergo transplant as their white counterparts.

Liver cancer has not received much attention in the United States until recently, said lead author Abby Siegel, MD, assistant professor of medicine, Columbia University. "We think, primarily because of the hepatitis C epidemic, the incidence has actually doubled in the United States over the last 30 years," she said at the 2006 Gastrointestinal Cancers Symposium (abstract 163).

Kaplan-Meier survival curves for transplant vs other treatment for hepatocellular carcinoma.

She noted that in mainly single-institution studies conducted among highly selected patients with hepatocellular carcinoma, namely, those meeting the Milan criteria (one tumor measuring 5 cm or less in diameter or three tumors each measuring less than 3 cm), the 5-year survival with transplantation is fairly high, about 75%, but it is unknown if this outcome bears out in broader populations.

To determine if the Milan criteria hold true among the general US population with hepatocellular cancer and also to assess predictors of liver transplantation among potentially eligible patients, Dr. Siegel and her colleagues analyzed Surveillance, Epidemiology, and End Results (SEER) data. "At the time that we did the study, SEER accounted for about 14% of the US population," she noted.

Analyses were based on 1,156 adults in the database who had nonmetastatic hepatocellular carcinoma measuring 5 cm or less in diameter that was diagnosed during the years 1998-2002. The SEER data align generally well though not perfectly with Milan criteria, providing only extent of disease (localized, regional, or distant) and tumor size, Dr. Siegel noted.

Patients were classified as to whether they received liver transplant; the nontransplanted group included patients who underwent resection or ablation, had chemotherapy or other therapies, or received only palliative care.

The patients' median age was 61 years, and nearly three-fourths were men, Dr. Siegel said. Some 45% were white, 29% were Asian, 17% Hispanic, and 9% African American. All of the patients had localized disease; 48% had low-grade tumors, and 81% did not have any vascular invasion.

Overall, 21% of the patients underwent transplantation, while the rest received some other treatment or only palliative care. The 5-year survival was 75% in the former group, compared with only about 12% in the latter one (see Figure).

Commenting on the excellent outcome obtained with transplantation, Dr. Siegel noted that the patients studied probably had features even less favorable than those of the Milan criteria. "They could perhaps have had more than three tumors as long as they were all localized to the liver, for instance," she explained.

Predictors of Transplant

In a multivariate analysis, several social and demographic factors significantly predicted transplantation:

Compared with white patients, black, Asian, and Hispanic patients had lower odds of transplantation (odds ratios, 0.48, 0.50, and 0.61, respectively).

Relative to patients aged 65 years or older, younger patients had markedly higher odds of transplant (5.79).

Married patients were about twice as likely as their single counterparts to undergo transplant (2.16), a finding likely related to greater social support.

Compared with patients in the western states, those in the northeastern and southern ones had lower odds of receiving a transplant (0.20 and 0.28).

As tumor size increased, the likelihood of transplantation decreased (0.47 with each 1-cm increase).

Year of diagnosis and sex did not significantly affect patients' chances of transplantation.

"Transplanted patients with nonmetastatic hepatocellular carcinoma have excellent long-term survival equaling that of the best single-institution studies, but we did find marked ethnic differences in receipt of transplants," she said. "We feel that these should be examined further—we should try to find out why these disparities exist and try to rectify them."

Racial Disparities

Commenting on factors that may contribute to the observed racial disparities, she noted that black patients typically have more advanced cancer by the time they are referred for evaluation for transplant. In addition, black patients more often have blood type B, making it harder to find a matching liver, although campaigns have succeeded in increasing organ donation among this racial group.

Looking at the broader picture, Dr. Siegel noted that about 17,000 people are currently on the waiting list for a liver transplant (for any reason), but the number of people donating livers has plateaued at a much lower value—about 5,000 per year. "This is a very scarce resource, and we need to try to allocate it as ethically as we can," she commented.

In concluding, Dr. Siegel offered advice for physicians who care for patients with hepatocellular carcinoma: "If there is any chance that a person could be a transplant candidate, it is important to have them evaluated at a center that offers transplant because it's clearly lifesaving for those who qualify and meet these criteria, and, as you can see, other treatment options are less than ideal."