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Multimodality Approach Improves Outcomes in Hepatocellular Carcinoma

With nationally and internationally recognized authorities in established modalities as well as experimental techniques, the treatment team for hepatocellular carcinoma and hilar cholangiocarcinoma at the Center for Liver Disease and Transplantation at NewYork-Presbyterian Hospital/Columbia University Medical Center is setting new standards for patient outcomes—including long-term survival—in resection, adjuvant therapies, and transplantation.

Robert S. Brown, Jr., MD, MPH

"It is natural for cancer centers to focus their attention toward what they do best at their center, but when you have a team with expertise on the full array of options, you can work together to do what is best for each patient," observed Robert S. Brown, Jr, MD, MPH. "This type of expertise also permits thinking that is outside of the box. In addition, with the team approach, it is simple to switch between modalities as the clinical situation changes."

Patients with liver and biliary tree cancers come to the Center through referrals from hepatologists, surgeons, oncologists, or other specialists; however, once they are referred, the case is automatically introduced into review by the multidisciplinary team that meets several times per week. Because of this collaboration, patients not only benefit from a group of experts agreeing on an optimal strategy from the perspective of very different disciplines, but there is also attention to the long-term implications of therapy. In liver cancer, successful downsizing of the tumor through adjunctive chemotherapy, radiation, or resection may mean a change in direction, such as liver transplant, in which the goal becomes cure rather than disease control.

"We have been able to consider transplant far outside of the traditional boundaries because the multimodality approach allows us to increase the proportion of liver cancer patients who are candidates for transplant," reported John F. Renz, MD, PhD. According to Dr. Renz, in unresectable but localized liver cancer, transplant may be the only way to prevent recurrence.

Among the innovative transplant programs currently being pursued at NewYork-Presbyterian/Columbia is one involving the treatment of hilar cholangiocarcinoma. Adapting an approach first pioneered at the Mayo Clinic, the protocol involves a regimen of chemoradiation to eliminate any systemic malignant cells, followed by transplant, which removes the primary tumor. The approach is experimental but promising, and it is expected to not only extend overall survival; it should also prevent late recurrence.

Transplant success at NewYork-Presbyterian/Columbia is not just a function of transplant skill. Drs. Brown and Renz credited the work of oncologists on the team, particularly Abby B. Siegel, MD. Dr. Siegel is involved in the design of numerous clinical trials with agents aimed at debulking cancers, which can render patients transplant candidates. Recently, she has been particularly active in studying anti-angiogenic agents, such as bevacizumab, which help deprive tumors of their blood supply.

"If you can provide a systemic therapy that ultimately permits the patient to undergo transplant, this is potentially lifesaving. Five-year survival in some series of patients with unresectable localized disease that have undergone transplantation has been 75% to 80%," Dr. Siegel observed. "We have been the primary study site or a participating study site in several trials with agents that act at the molecular level, which can mean shrinkage of tumor with relatively modest side effects relative to traditional chemotherapy agents."

Dr. Siegel has recently become interested in evidence that Caucasians with liver cancer are more likely than other racial groups to undergo transplant. Drawn from the United States Surveillance, Epidemiology, and End Results (SEER) registry, the data suggest that overall outcome could be improved by looking for opportunities to increase liver transplant in patient populations that now have low rates (Table). This is less likely to be the product of denying liver transplant in specific groups than more complex issues, such as delayed diagnosis that reduces the number of candidates for transplant. Addressing obstacles to transplant may have important ramifications for survival.

"Because we serve a large Hispanic population, we have been trying hard to understand and eliminate any barriers to transplant in this and other historically underserved populations," Dr. Siegel reported. There is a particular opportunity for improving this record in a system in which the multimodality approach to care is exercised in every patient. Dr. Brown also emphasized the importance of providing the same high standard of care to every patient.

"The Hospital is a one-stop exposure to specialists from multiple fields, allowing every option to be fully explored before the best approach is selected," Dr. Brown noted. "With advances in many fields being pursued simultaneously, this is the way care should be offered."