Overview

The following is a general overview of the treatment of hepatocellular carcinoma, the most common type of primary liver cancer. Choice of treatment will depend on the extent and location of the cancer, the health of the liver, and the overall health of the patient.

Circumstances unique to each patient’s situation influence which treatment or treatments are utilized. The potential benefits of combination treatment, participation in a clinical trial, or standard treatment must be carefully balanced with the potential risks. The information on this Web site is intended to help educate patients about their treatment options and to facilitate a mutual or shared decision-making process with their treating cancer physician.

Most new treatments are developed in clinical trials. Clinical trials are studies that evaluate the effectiveness of new drugs or treatment strategies. The development of more effective cancer treatments requires that new and innovative therapies be evaluated with cancer patients. Participation in a clinical trial may offer access to better treatments and advance the existing knowledge about treatment of this cancer. Clinical trials are available for most stages of cancer. Patients who are interested in participating in a clinical trial should discuss the risks and benefits of clinical trials with their physician. To ensure that you are receiving the optimal treatment of your cancer, it is important to stay informed and follow the cancer news in order to learn about new treatments and the results of clinical trials.

Surgical Treatment of Hepatocellular Carcinoma

For patients who are healthy enough to undergo surgery and who have early-stage cancer confined to the liver, treatment may involve surgical resection or liver transplantation.

Resection: Resection refers to surgical removal of the cancer and some surrounding normal tissue. This is often the treatment of choice in patients without cirrhosis.[1] Although resection is potentially curative, an estimated 70% of patients will develop a cancer recurrence during the first five years after treatment. Furthermore, resection is only possible when the remaining part of the liver is healthy enough to function on its own after surgery. For many patients with cirrhosis or other liver disease, this will not be the case and other treatment options will need to be considered.

Liver transplantation: For selected patients who have cancer that is confined to the liver but cannot be resected, liver transplantation may be an option. A benefit of liver transplantation is that it treats not only the cancer but also any underlying liver disease such as cirrhosis. Because the number of donor livers is limited, however, liver transplantation is generally reserved for those patients who are expected to have the best survival and the lowest risk of recurrence after transplantation. According to the commonly used “Milan criteria,” for example, transplant candidates should have a single liver nodule that measures no more than 5 cm or two or three nodules that measure no more than 3 cm each. These criteria are fairly restrictive, and the question of whether and how to expand the criteria to include more patients is currently being evaluated.[2]

Non-surgical Treatment of Hepatocellular Carcinoma

Even when the cancer is confined to the liver, not all patients will be candidates for surgery. Fortunately, there are several non-surgical treatment approaches available.

Ablation: Ablation refers to the destruction of the tumor using techniques such as injection of alcohol into the tumor (percutaneous ethanol injection) or use of electrical energy and heat (radiofrequency ablation). Ablation tends to be most effective when tumors are small and limited in numbers.[3]

Chemoembolization: Cancers rely on an adequate blood supply in order to grow and survive. The blood supply to liver tumors is provided primarily by the hepatic artery. In the process of transarterial chemoembolization (TACE), chemotherapy is injected into the branch of the hepatic artery that supplies the tumor. This allows the chemotherapy to concentrate in the area of the tumor. In addition, the hepatic artery is blocked (embolized) in order to reduce blood supply to the tumor. This procedure is not curative, but it can improve survival.[4] In general, patients must have adequate blood flow through the portal vein (the other main blood supply to the liver) in order to undergo TACE.[5]

Nexavar® (sorafenib): The targeted therapy Nexavar is the first systemic therapy to improve survival in hepatocellular carcinoma, and is now a standard approach to treatment among patients with advanced hepatocellular carcinoma. Nexavar inhibits biological pathways involved in cell proliferation and the development of new blood vessels. In a Phase III clinical trial among patients with advanced hepatocellular carcinoma and preserved liver function, median overall survival was 10.7 months among patients treated with Nexavar compared with 7.9 months among patients treated with placebo.[6] The most common side effects of Nexavar were diarrhea, weight loss, and hand-foot skin reaction. There is limited information about the safety and efficacy of Nexavar among patients with poor liver function.[7]

Strategies to Improve Treatment

The development of more effective cancer treatments requires that new and innovative therapies be evaluated with cancer patients. Clinical trials are studies that evaluate the effectiveness of new drugs or treatment strategies. Future progress in the treatment of hepatocellular carcinoma will result from the continued evaluation of new treatments in clinical trials. Participation in a clinical trial may offer patients access to better treatments and advance the existing knowledge about treatment of this cancer. Patients who are interested in participating in a clinical trial should discuss the risks and benefits of clinical trials with their physician.

Adjuvant therapy: Recurrence rates after treatment with resection or ablation are high, highlighting the importance of finding effective adjuvant treatments (treatments given after the primary treatment to reduce the risk of recurrence). Although the search for effective adjuvant therapy for hepatocellular carcinoma has been frustrating, planned studies of newer agents such as Nexavar may hold promise.

New targeted therapies: The approval of Nexavar for selected patients with hepatocellular carcinoma has prompted interest in the role of several other targeted therapies. Targeted therapies being evaluated in clinical trials among patients with hepatocellular carcinoma include Sutent® (sunitinib), Avastin® (bevacizumab), Tarceva® (erlotinib), and Tykerb® (lapatinib).

Treatment prior to liver transplantation: Due to the limited availability of donor livers, wait times for a liver transplant can be long. During the wait the cancer may progress to the extent that the patient is no longer eligible for transplantation. In order to control cancer growth during the wait for a donor liver, patients may receive treatment such as ablation or chemoembolization.[8] The effect of these treatments on the survival of transplant candidates remains uncertain.

Living donor liver transplantation: Liver transplantation from a living donor is one strategy to increase the availability of donor livers. In this procedure a living person donates part of their liver (usually the right hepatic lobe if the recipient is an adult).[9] The primary disadvantage of this procedure is the risk to the donor. 

Identifying candidates for liver transplantation: Identification of patients who are candidates for liver transplantation remains challenging. The goal is to identify those patients who are most likely to benefit. In part, this involves determining which patients are least likely to experience a cancer recurrence following transplantation. Traditional criteria consider factors such as the number and size of liver tumors, but it may be possible to improve upon these criteria by assessing specific biological characteristics of the tumor.[10] Research on this question is underway.

Radiation therapy: Historically, radiation therapy has played a limited role in the treatment of hepatocellular carcinoma because of the damage it caused to normal liver tissue. Advances in radiation therapy, however, have allowed for more targeted delivery of effective doses of radiation. These advances include newer approaches to the delivery of external radiation therapy, [11] as well as techniques such as TheraSphere® that deliver radiation directly to the liver. TheraSphere involves the use of microscopic glass beads that contain a radioactive material. The beads are delivered through a catheter into the hepatic artery. The beads become trapped in the blood vessels that feed the tumor and deliver radiation to the tumor.

References:


[1] Bruix J, Sherman M. Management of hepatocellular carcinoma. Hepatology. 2005;42:1208-1236.

[2] Mazzaferro V, Llovet JM, Miceli R et al. Predicting survival after liver transplantation in patients with hepatocellular carcinoma beyond the Milan criteria: a retrospective, exploratory analysis. Lancet Oncology. 2009;10:35-43.

[3] Llovet JM, Bruix J. Novel advances in the management of hepatocellular carcinoma in 2008. Journal of Hepatology. 2008;48:S20-S37.

[4] Llovet JM, Bruix J. Systematic review of randomized trials for unresectable hepatocellular carcinoma: chemoembolization improves survival. Hepatology. 2003;37:429-442.

[5] Bruix J, Sherman M. Management of hepatocellular carcinoma. Hepatology. 2005;42:1208-1236.

[6] Llovet JM, Ricci S, Mazzaferro V et al. Sorafenib in advanced hepatocellular carcinoma. New England Journal of Medicine. 2008;359:378-90.

[7] Kelley RK, Venook AP. Sorafenib in hepatocellular carcinoma: separating the hype from the hope. Journal of Clinical Oncology. 2008;26:5845-5848.

[8] Llovet JM, Schwartz M, Mazzaferro V. Resection and liver transplantation for hepatocellular carcinoma. Seminars in Liver Disease. 2005;25:181-200.

[9] Trotter JF, Wachs M, Everson GT, Kam I. Adult-to-adult transplantation of the right hepatic lobe from a living donor. New England Journal of Medicine. 2002;346:1074-1082.

[10] Neuberger J. Liver-cell cancer and transplantation. Lancet Oncology. 2009;10:5-7.

[11] Hawkins MA, Dawson LA. Radiation therapy for hepatocellular carcinoma: from palliation to cure. Cancer. 2006;106:1653-63.

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