Cancer Information

Adult Primary Liver Cancer Treatment (PDQ®)


General Information About Adult Primary Liver Cancer

Note: Some citations in the text of this section are followed by a level of evidence. The PDQ editorial boards use a formal ranking system to help the reader judge the strength of evidence linked to the reported results of a therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence for more information.)

Incidence and Mortality

Estimated new cases and deaths from liver and intrahepatic bile duct cancer in the United States in 2012:[1]

  • New cases: 28,720.
  • Deaths: 20,550.

Hepatocellular carcinoma is a tumor that is relatively uncommon in the United States, although its incidence is rising, principally in relation to the spread of hepatitis C infection.[2] It is the most common cancer in some parts of the world, with more than 1 million new cases diagnosed each year. Hepatocellular carcinoma is potentially curable by surgical resection, but surgery is the treatment of choice for only the small fraction of patients with localized disease.[3] Prognosis depends on the degree of local tumor replacement and the extent of liver function impairment. Therapy other than surgical resection is best administered as part of a clinical trial. Such trials evaluate the efficacy of systemic or infusional chemotherapy, hepatic artery ligation or embolization, percutaneous ethanol injection, radiofrequency ablation, cryotherapy, and radiolabeled antibodies, often in conjunction with surgical resection and/or radiation therapy. In some studies of these approaches, long remissions have been reported.[3] A few patients may be candidates for liver transplantation, but the limited availability of livers for transplantation restricts the use of this approach.[4] Hepatocellular carcinoma can coexist with bile duct cancer (cholangiocarcinoma).[5]

Risk factors

Hepatocellular carcinoma is associated with cirrhosis in 50% to 80% of patients; 5% of cirrhotic patients eventually develop hepatocellular cancer, which is often multifocal.

Hepatitis B infection [3][6] and hepatitis C infection [7] appear to be the most significant causes of hepatocellular carcinoma worldwide, particularly in patients with continuing antigenemia and in those who have chronic active hepatitis. A series found that male patients older than 50 years who have both hepatitis B and hepatitis C infection may be at particularly high risk for hepatocellular cancer.[8][Level of evidence: 3iiiDiv] There is evidence that patients with both hepatitis B and hepatitis C infection who consume more than 80 grams of alcohol per day have an increased risk of developing cancer (odds ratio [OR] = 7.3) when compared to patients who abstain from alcohol.[9] Additionally, having a first-degree relative with hepatitis B plus hepatocellular carcinoma is associated with an increased risk (OR = 2.41) for family members who are hepatitis B carriers.[10]

Aflatoxin has also been implicated as a factor in the etiology of primary liver cancer in parts of the world where this mycotoxin occurs in high levels in ingested food.[6][11] Workers who were exposed to vinyl chloride before controls on vinyl chloride dust were instituted developed sarcomas in the liver, most commonly angiosarcomas. Other sarcomas of smooth muscular and vascular origin are also found.

In the United States, obesity has emerged as a very important risk factor for hepatocellular carcinoma and is the main contributor of nonalcoholic steatohepatitis, which may be related to an increase in the rate of hepatocellular carcinoma.[12]

The primary symptoms of hepatocellular carcinoma are those of a hepatic mass. Among patients with underlying cirrhotic disease, a progressive increase in alpha-fetoprotein (AFP) and/or in alkaline phosphatase or a rapid deterioration of hepatic function may be the only clue to the presence of the neoplasm. Infrequently, patients with this disease have polycythemia, hypoglycemia, hypercalcemia, or dysfibrinogenemia. (For more information on Hypercalcemia, refer to the PDQ summary of the same name.)

Prognostic factors

The biologic marker AFP is useful for the diagnosis of this neoplasm. By a radioimmunoassay technique, 50% to 70% of patients in the United States who have hepatocellular carcinoma have elevated levels of AFP. However, patients with other malignancies (germ cell carcinoma and, rarely, pancreatic and gastric carcinoma) also demonstrate elevated serum levels of this protein. AFP levels have been shown in studies such as RTOG-8301 to be prognostically important, with the median survival of AFP-negative patients significantly longer than that of AFP-positive patients.[13][14] Other prognostic variables include performance status, liver functions,[15] and the presence or absence of cirrhosis and its severity in relation to the Child-Pugh classification.[16]

Patients scheduled for possible resection require preoperative assessment with angiography in conjunction with helical computed tomographic (CT) scan or magnetic resonance imaging (MRI) with magnetic resonance angiography; these scans have obviated the need for angiography in most patients. Information on the arterial anatomy is helpful for the operating surgeon and may eliminate some patients from consideration for resection. The presence of tumor thrombi in the hepatic veins, the inferior vena cava, or the portal vein can significantly alter treatment approaches. Dynamic CT and MRI scans can document the relationship of the tumor to the hepatic and portal veins (and, on occasion, involvement of these structures), delineating tumors for which the chances for surgical cure are remote.[17] Laparoscopic evaluation may detect metastatic disease, bilobar disease, or inadequate liver remnant, and therefore obviate the need for open surgical exploration.[18]

Related Summaries

Other PDQ summaries containing information related to adult primary liver cancer include the following:

  • Childhood Liver Cancer
  • Liver (Hepatocellular) Cancer Screening
1American Cancer Society.: Cancer Facts and Figures 2012. Atlanta, Ga: American Cancer Society, 2012. Available online. Last accessed January 4, 2013.2El-Serag HB, Mason AC: Rising incidence of hepatocellular carcinoma in the United States. N Engl J Med 340 (10): 745-50, 1999.3Mor E, Kaspa RT, Sheiner P, et al.: Treatment of hepatocellular carcinoma associated with cirrhosis in the era of liver transplantation. Ann Intern Med 129 (8): 643-53, 1998.4Klintmalm GB: Liver transplantation for hepatocellular carcinoma: a registry report of the impact of tumor characteristics on outcome. Ann Surg 228 (4): 479-90, 1998.5Jarnagin WR, Weber S, Tickoo SK, et al.: Combined hepatocellular and cholangiocarcinoma: demographic, clinical, and prognostic factors. Cancer 94 (7): 2040-6, 2002.6Blumberg BS, Larouzé B, London WT, et al.: The relation of infection with the hepatitis B agent to primary hepatic carcinoma. Am J Pathol 81 (3): 669-82, 1975.7Tsukuma H, Hiyama T, Tanaka S, et al.: Risk factors for hepatocellular carcinoma among patients with chronic liver disease. N Engl J Med 328 (25): 1797-801, 1993.8Chiaramonte M, Stroffolini T, Vian A, et al.: Rate of incidence of hepatocellular carcinoma in patients with compensated viral cirrhosis. Cancer 85 (10): 2132-7, 1999.9Tagger A, Donato F, Ribero ML, et al.: Case-control study on hepatitis C virus (HCV) as a risk factor for hepatocellular carcinoma: the role of HCV genotypes and the synergism with hepatitis B virus and alcohol. Brescia HCC Study. Int J Cancer 81 (5): 695-9, 1999.10Yu MW, Chang HC, Liaw YF, et al.: Familial risk of hepatocellular carcinoma among chronic hepatitis B carriers and their relatives. J Natl Cancer Inst 92 (14): 1159-64, 2000.11Alpert ME, Hutt MS, Wogan GN, et al.: Association between aflatoxin content of food and hepatoma frequency in Uganda. Cancer 28 (1): 253-60, 1971.12El-Serag HB: Hepatocellular carcinoma. N Engl J Med 365 (12): 1118-27, 2011.13Stillwagon GB, Order SE, Guse C, et al.: Prognostic factors in unresectable hepatocellular cancer: Radiation Therapy Oncology Group Study 83-01. Int J Radiat Oncol Biol Phys 20 (1): 65-71, 1991.14Izumi R, Shimizu K, Kiriyama M, et al.: Alpha-fetoprotein production by hepatocellular carcinoma is prognostic of poor patient survival. J Surg Oncol 49 (3): 151-5, 1992.15Yamashita Y, Takahashi M, Koga Y, et al.: Prognostic factors in the treatment of hepatocellular carcinoma with transcatheter arterial embolization and arterial infusion. Cancer 67 (2): 385-91, 1991.16Nakakura EK, Choti MA: Management of hepatocellular carcinoma. Oncology (Huntingt) 14 (7): 1085-98; discussion 1098-102, 2000.17Karl RC, Morse SS, Halpert RD, et al.: Preoperative evaluation of patients for liver resection. Appropriate CT imaging. Ann Surg 217 (3): 226-32, 1993.18Lo CM, Lai EC, Liu CL, et al.: Laparoscopy and laparoscopic ultrasonography avoid exploratory laparotomy in patients with hepatocellular carcinoma. Ann Surg 227 (4): 527-32, 1998.

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Cellular Classification of Adult Primary Liver Cancer

Malignant tumors of the liver are primarily adenocarcinomas, with two major cell types: hepatocellular and cholangiocarcinoma.

Histologic classification is as follows:

  • Hepatocellular carcinoma (liver cell carcinoma).
  • Hepatocellular carcinoma (fibrolamellar variant). The fibrolamellar variant is important because an increased proportion of these patients may be cured if the tumor can be resected. It is more frequent in young women. It also generally exhibits a slower clinical course than the more common hepatocellular carcinoma.
  • Cholangiocarcinoma (intrahepatic bile duct carcinoma).
  • Mixed hepatocellular cholangiocarcinoma.
  • Undifferentiated.

Hepatoblastoma rarely occurs in adults.

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Stage Information for Adult Primary Liver Cancer

Note: The American Joint Committee on Cancer has recently published a new edition of the AJCC Cancer Staging Manual, which includes revisions to the staging for this disease. The PDQ Adult Treatment Editorial Board, which is responsible for maintaining this summary, is currently reviewing the new staging to determine the changes that need to be made in the summary. In addition to updating this Stage Information section, additional changes may need to be made to other parts of this summary to ensure that it is up-to-date. The changes will be made as soon as possible.

TNM Definitions

    Primary tumor (T)
  • TX: Primary tumor cannot be assessed
  • T0: No evidence of primary tumor
  • T1: Solitary tumor without vascular invasion
  • T2: Solitary tumor with vascular invasion or multiple tumors none more than 5 cm
  • T3: Multiple tumors more than 5 cm or tumor involving a major branch of the portal or hepatic vein(s)
  • T4: Tumor(s) with direct invasion of adjacent organs other than the gallbladder or with perforation of the visceral peritoneum
    Regional lymph nodes (N)
  • NX: Regional lymph nodes cannot be assessed
  • N0: No regional lymph node metastasis
  • N1: Regional lymph node metastasis

The regional lymph nodes are the hilar (i.e., those in the hepatoduodenal ligament, hepatic, and periportal nodes). Regional lymph nodes also include those along the inferior vena cava, hepatic artery, and portal vein. Any lymph node involvement beyond these nodes is considered distant metastasis and should be coded as M1. Involvement of the inferior phrenic lymph nodes should also be considered M1.

    Distant metastasis (M)
  • MX: Distant metastasis cannot be assessed
  • M0: No distant metastasis
  • M1: Distant metastasis

Metastases occur most frequently in bones and lungs. Tumors may extend through the capsule to adjacent organs (adrenal glands, diaphragm, and colon) or may rupture, causing acute hemorrhage and peritoneal carcinomatosis.

The T classification is based on the results of multivariate analyses of factors affecting prognosis after resection of liver carcinomas. The classification considers the presence or absence of vascular invasion (as assessed radiographically or pathologically), the number of tumor nodules (single vs. multiple), and the size of the largest tumor (≤ 5 cm vs. > 5 cm). For pathologic classification, vascular invasion includes gross as well as microscopic involvement of vessels. Major vascular invasion (T3) is defined as invasion of the branches of the main portal vein (right or left portal vein; this does not include sectoral or segmental branches) or as invasion of one or more of the 3 hepatic veins (right, middle, or left). Multiple tumors include satellitosis, multifocal tumors, and intrahepatic metastases. Invasion of adjacent organs other than the gallbladder or with perforation of the visceral peritoneum is considered T4.

AJCC Stage Groupings

    Stage I
  • T1, N0, M0
    Stage II
  • T2, N0, M0
    Stage IIIA
  • T3, N0, M0
    Stage IIIB
  • T4, N0, M0
    Stage IIIC
  • Any T, N1, M0
    Stage IV
  • Any T, any N, M1

For purposes of treatment, patients with liver cancer are grouped into 1 of 3 groups: localized resectable, localized unresectable, or advanced disease. These groups are described with the following AJCC stage groupings:

Localized Resectable Adult Primary Liver Cancer

(Selected T1 and T2; N0; M0)

Localized resectable liver cancer is confined to a solitary mass in a portion of the liver, or a limited number of tumors confined to one lobe, that allows the possibility of complete surgical removal of the tumor with a margin of normal liver. Liver function tests are usually normal or minimally abnormal, and there should be no evidence of cirrhosis beyond Child class A or chronic hepatitis. Only a small percentage of liver cancer patients will prove to have such localized resectable disease. Preoperative assessment that includes 3-phase helical computed tomography and/or magnetic resonance scanning should be directed toward determining the presence of extension of tumor across interlobar planes, involvement of the hepatic hilus, or encroachment on the vena cava. A resected specimen should ideally contain a 1 cm margin of normal liver. Patients with cirrhosis and resectable tumors are also eligible for liver transplantation;[1] if eligible, sometimes other measures are instituted until liver transplantation becomes available.

Localized and Locally Advanced Unresectable Adult Primary Liver Cancer

(Selected T1, T2, T3, and T4; N0; M0)

Localized and locally advanced unresectable liver cancer appears to be confined to the liver, but surgical resection of the entire tumor is not appropriate because of location within the liver or concomitant medical conditions (such as cirrhosis). These patients may be considered for liver transplantation.[2][3][4] For other patients, percutaneous or intraoperative radiofrequency ablation (RFA) or other forms of ablation of small (<3 cm) appropriately located tumors, or transarterial chemoembolization (TACE) may be options.[5]

Advanced Adult Primary Liver Cancer

(Any T, N1 or M1)

Advanced liver cancer is present in both lobes of the liver or has metastasized to distant sites. Median survival is usually 2 to 4 months. The most common metastatic sites of hepatocellular cancer are the lungs and bone. Multifocal disease in the liver is common, particularly when cirrhosis or chronic hepatitis is present. Chemoembolization has been beneficial in selected patients who have no extrahepatic metastases.[6]

1Mazzaferro V, Regalia E, Doci R, et al.: Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis. N Engl J Med 334 (11): 693-9, 1996.2Llovet JM, Burroughs A, Bruix J: Hepatocellular carcinoma. Lancet 362 (9399): 1907-17, 2003.3Bruix J, Sherman M; Practice Guidelines Committee, American Association for the Study of Liver Diseases.: Management of hepatocellular carcinoma. Hepatology 42 (5): 1208-36, 2005.4Bruix J, Sherman M, Llovet JM, et al.: Clinical management of hepatocellular carcinoma. Conclusions of the Barcelona-2000 EASL conference. European Association for the Study of the Liver. J Hepatol 35 (3): 421-30, 2001.5Pawlik TM, Reyes DK, Cosgrove D, et al.: Phase II trial of sorafenib combined with concurrent transarterial chemoembolization with drug-eluting beads for hepatocellular carcinoma. J Clin Oncol 29 (30): 3960-7, 2011.6Tanaka K, Nakamura S, Numata K, et al.: The long term efficacy of combined transcatheter arterial embolization and percutaneous ethanol injection in the treatment of patients with large hepatocellular carcinoma and cirrhosis. Cancer 82 (1): 78-85, 1998.

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Localized Resectable Adult Primary Liver Cancer

Note: Some citations in the text of this section are followed by a level of evidence. The PDQ editorial boards use a formal ranking system to help the reader judge the strength of evidence linked to the reported results of a therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence for more information.)

For patients with selected T1 or T2; N0; M0 disease.

Standard treatment options:

  • Surgery: Resection of localized hepatocellular cancer varies from segmental resection to trisegmental (80% of liver) resection. In series of carefully selected patients, partial hepatectomy has resulted in a 5-year survival of 30% to 40%, with median survivals approaching 3 years.[1] In a retrospective study of patients with intrahepatic cholangiocarcinoma, hepatic resection demonstrated a 5-year survival of 23% and a tumor-free survival of 11%.[2][Level of evidence: 3iiiDii] Hepatic carcinoma is frequently multifocal and may involve multiple sites throughout the liver at the time of exploration, even when a dominant mass is found on preoperative assessment. Preoperative assessment should also include a search for extrahepatic metastases, since this condition will also preclude the planned hepatic resection. Intraoperative ultrasound assessment of the liver often finds satellite or second lesions.[3] Resection that involves more than a nonanatomic wedge of liver is poorly tolerated and leads to a high mortality rate in patients with severe cirrhosis. Severe cirrhosis may be a contraindication to major hepatic resection but may not contraindicate hepatic transplantation.[4][5][6][7] Hepatic transplantation for hemangioendothelioma, fibrolamellar hepatocellular carcinoma, and small (<5 cm) hepatocellular carcinoma in patients with or without cirrhosis has been associated with 5-year survivals of 20% to 30%.[8][Level of evidence: 3iiiA];[9]

Treatment options under clinical evaluation:

  • Chemotherapy or biologic therapy: Because of the high proportion of patients who experience relapse following surgery for localized hepatic cancer, adjuvant approaches have been employed using chemoembolization, regional arterial infusion of the liver or systemic therapy with chemotherapeutic agents. One randomized trial of 43 patients suggested improved survival with adjuvant injection of a single dose (1,850 MBq) of I-131 lipiodol via the hepatic artery. Median disease-free survival in the treatment group was 57 months compared to 13.6 months in the group that did not receive treatment beyond resection (P = .037).[10][Level of evidence: 1iiA,1iiB] Lipiodol was nontoxic, but required thyroid suppression before and after surgery. Enrollment in this trial was prematurely terminated because of early differences in survival between the treatment and control arms. Therefore, the results must be considered preliminary and will require confirmation. Adoptive immunotherapy with interleukin-2 and anti-CD3 activated autologous lymphocytes was found to have lengthened recurrence-free survival, but not overall survival, in one study.[11][Level of evidence: 1iiDiv] Localized recurrences in the liver may occasionally be successfully treated by re-resection.[12][13]

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with localized resectable adult primary liver cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

1Fong Y, Sun RL, Jarnagin W, et al.: An analysis of 412 cases of hepatocellular carcinoma at a Western center. Ann Surg 229 (6): 790-9; discussion 799-800, 1999.2Ohtsuka M, Ito H, Kimura F, et al.: Extended hepatic resection and outcomes in intrahepatic cholangiocarcinoma. J Hepatobiliary Pancreat Surg 10 (4): 259-64, 2003.3Karl RC, Choi J, Yeatman TJ, et al.: Role of Computed Tomographic Arterial Portography and Intraoperative Ultrasound in the Evaluation of Patients for Resectability of Hepatic Lesions. J Gastrointest Surg 1 (2): 152-158, 1997.4Starzl TE, Koep LJ, Weil R 3rd, et al.: Right trisegmentectomy for hepatic neoplasms. Surg Gynecol Obstet 150 (2): 208-14, 1980.5Nagorney DM, van Heerden JA, Ilstrup DM, et al.: Primary hepatic malignancy: surgical management and determinants of survival. Surgery 106 (4): 740-8; discussion 748-9, 1989.6MacIntosh EL, Minuk GY: Hepatic resection in patients with cirrhosis and hepatocellular carcinoma. Surg Gynecol Obstet 174 (3): 245-54, 1992.7Hemming AW, Cattral MS, Reed AI, et al.: Liver transplantation for hepatocellular carcinoma. Ann Surg 233 (5): 652-9, 2001.8Pichlmayr R, Weimann A, Oldhafer KJ, et al.: Appraisal of transplantation for malignant tumours of the liver with special reference to early stage hepatocellular carcinoma. Eur J Surg Oncol 24 (1): 60-7, 1998.9Yamamoto J, Iwatsuki S, Kosuge T, et al.: Should hepatomas be treated with hepatic resection or transplantation? Cancer 86 (7): 1151-8, 1999.10Lau WY, Leung TW, Ho SK, et al.: Adjuvant intra-arterial iodine-131-labelled lipiodol for resectable hepatocellular carcinoma: a prospective randomised trial. Lancet 353 (9155): 797-801, 1999.11Takayama T, Sekine T, Makuuchi M, et al.: Adoptive immunotherapy to lower postsurgical recurrence rates of hepatocellular carcinoma: a randomised trial. Lancet 356 (9232): 802-7, 2000.12Nakajima Y, Ko S, Kanamura T, et al.: Repeat liver resection for hepatocellular carcinoma. J Am Coll Surg 192 (3): 339-44, 2001.13Neeleman N, Andersson R: Repeated liver resection for recurrent liver cancer. Br J Surg 83 (7): 893-901, 1996.

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Localized and Locally Advanced Unresectable Adult Primary Liver Cancer

Note: Some citations in the text of this section are followed by a level of evidence. The PDQ editorial boards use a formal ranking system to help the reader judge the strength of evidence linked to the reported results of a therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence for more information.)

For selected patients with T1, T2, T3, or T4; N0; M0 disease.

Patients whose tumors are localized but unresectable due to location in the liver, concomitant medical considerations (such as cirrhosis), or even limited bilateral tumors, may be candidates for chemoembolization, cryosurgery, percutaneous ethanol injection, or radiofrequency ablation for cancers smaller than 5 cm. Survivals equivalent to resection have been reported.[1] One randomized trial in cirrhosis patients with small hepatocellular carcinomas demonstrated improved local recurrence-free survival in patients who underwent radiofrequency ablation as compared to percutaneous ethanol injections as their only form of treatment,[2][Level of evidence: 1iiDiii] but overall survival was not changed.[2][Level of evidence: 1iiA]

Clinical trials that use systemic chemotherapy, regional chemotherapy, and/or labeled or radiolabeled antibodies have demonstrated remission of unresectable hepatoma. Other approaches include embolization of the hepatic artery with gelatin foam powder or muscle fragments and chemotherapy, usually doxorubicin. These approaches often produce central tumor necrosis, reduction in tumor size, and relief of pain, but the benefits are usually transient. Any interference with arterial blood supply (including infusion chemotherapy) may be associated with significant morbidity and is contraindicated in the presence of portal hypertension, portal vein thrombosis, or clinical jaundice. A randomized study of chemoembolization versus conservative treatment found no survival advantage for chemoembolization.[3] This study was terminated early and was underpowered to detect any but large survival differences.

Standard treatment options:

  1. Radiofrequency ablation, chemoembolization, cryosurgery, or percutaneous ethanol injection: These techniques may be used in patients with small (<5 cm), localized, unresectable tumors.[1][4][5][6][7][8]
  2. Liver transplantation: For selected patients with localized unresectable hepatoma, particularly patients with fibrolamellar hepatomas, liver transplantation may offer a potentially curative treatment option.[9]
  3. Chemotherapy (regional infusion of the liver): Chemotherapeutic agents may be infused with a subcutaneous portal or implantable pump via a catheter placed in the hepatic artery. Older studies that use standard agents have demonstrated responses in 15% to 30% of such cases, but newer agents and techniques (i.e., biodegradable microspheres) have been evaluated in pilot trials,[10][11][12] as has regional chemotherapy with external-beam radiation therapy.[13] Many patients are not candidates for these approaches, which often require surgical intervention.
  4. Systemic chemotherapy and/or targeted therapy: Prior to the SHARP trial (NCT00105443), durable remissions had rarely been reported, and randomized series had shown no significant survival benefits when compared with no treatment. In the SHARP trial, 602 patients with advanced hepatocellular carcinoma (slightly less than 50% of the patients in each group had carcinomas that were confined to the liver but were unresectable and had extrahepatic spread) who had not received prior systemic treatment were assigned to receive either sorafenib 400 mg twice daily or placebo.[14] All but 20 patients had Childs-Pugh A liver disease score; 13% were women. After 321 deaths, the median survival was significantly longer in the sorafenib group (10.7 months vs. 7.9 months on placebo; hazard ratio [HR] favoring sorafenib = 0.69; 95% confidence interval [CI], 0.55–0.87; P < .001).[14][Level of evidence: 1iA] While median time to symptoms was not significantly different, the percent achieving radiologic responses was higher in the sorafenib group. A subsequent similar trial conducted with 271 patients from 23 centers in China, South Korea, and Taiwan with a 2:1 randomization on sorafenib achieved a median overall survival rate of 6.5 months on sorafenib versus 4.2 months on placebo (HR = 0.68; 95% CI, 0.50–0.93; P = .014).[15] Adverse events attributed to sorafenib in both of these trials included hand-foot skin reactions and diarrhea. These studies establish a role for sorafenib in locally advanced as well as advanced hepatocellular cancers extending beyond the liver, which are not amenable to regional modalities. Studies are ongoing to evaluate the role of sorafenib after transarterial chemoembolization (TACE), with chemotherapy, or in the presence of more advanced liver disease.
  5. Surgery, chemotherapy, and radiation therapy: These modalities may be combined in clinical trials for patients with a dominant hepatic mass and multifocal involvement with small amounts of tumor; surgical resection, radiofrequency ablation, or cryosurgery of the mass may be followed by hepatic infusion of the remaining liver with chemotherapeutic agents alone or in combination with hyperthermia, radiation, or radiation with radiosensitizers.[1] Chemotherapy plus radiation has also been used to shrink tumors prior to resection.[16] However, the whole liver is not tolerant of large doses of radiation therapy.
  6. Radiosensitizers and external-beam radiation therapy without chemotherapy: The relative radiosensitivity of normal liver tissue compared with tumor tissue must always be considered when radiation therapy is contemplated.[17]

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with localized unresectable adult primary liver cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

1Zhou XD, Tang ZY: Cryotherapy for primary liver cancer. Semin Surg Oncol 14 (2): 171-4, 1998.2Lencioni RA, Allgaier HP, Cioni D, et al.: Small hepatocellular carcinoma in cirrhosis: randomized comparison of radio-frequency thermal ablation versus percutaneous ethanol injection. Radiology 228 (1): 235-40, 2003.3A comparison of lipiodol chemoembolization and conservative treatment for unresectable hepatocellular carcinoma. Groupe d'Etude et de Traitement du Carcinome Hépatocellulaire. N Engl J Med 332 (19): 1256-61, 1995.4Livraghi T, Goldberg SN, Lazzaroni S, et al.: Small hepatocellular carcinoma: treatment with radio-frequency ablation versus ethanol injection. Radiology 210 (3): 655-61, 1999.5Tanaka K, Nakamura S, Numata K, et al.: The long term efficacy of combined transcatheter arterial embolization and percutaneous ethanol injection in the treatment of patients with large hepatocellular carcinoma and cirrhosis. Cancer 82 (1): 78-85, 1998.6Livraghi T, Bolondi L, Lazzaroni S, et al.: Percutaneous ethanol injection in the treatment of hepatocellular carcinoma in cirrhosis. A study on 207 patients. Cancer 69 (4): 925-9, 1992.7Livraghi T, Benedini V, Lazzaroni S, et al.: Long term results of single session percutaneous ethanol injection in patients with large hepatocellular carcinoma. Cancer 83 (1): 48-57, 1998.8Curley SA, Izzo F, Delrio P, et al.: Radiofrequency ablation of unresectable primary and metastatic hepatic malignancies: results in 123 patients. Ann Surg 230 (1): 1-8, 1999.9Hemming AW, Cattral MS, Reed AI, et al.: Liver transplantation for hepatocellular carcinoma. Ann Surg 233 (5): 652-9, 2001.10Ensminger W, Niederhuber J, Dakhil S, et al.: Totally implanted drug delivery system for hepatic arterial chemotherapy. Cancer Treat Rep 65 (5-6): 393-400, 1981 May-Jun.11Dakhil S, Ensminger W, Cho K, et al.: Improved regional selectivity of hepatic arterial BCNU with degradable microspheres. Cancer 50 (4): 631-5, 1982.12Choi BI, Kim HC, Han JK, et al.: Therapeutic effect of transcatheter oily chemoembolization therapy for encapsulated nodular hepatocellular carcinoma: CT and pathologic findings. Radiology 182 (3): 709-13, 1992.13Epstein B, Ettinger D, Leichner PK, et al.: Multimodality cisplatin treatment in nonresectable alpha-fetoprotein-positive hepatoma. Cancer 67 (4): 896-900, 1991.14Llovet JM, Ricci S, Mazzaferro V, et al.: Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 359 (4): 378-90, 2008.15Cheng AL, Kang YK, Chen Z, et al.: Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial. Lancet Oncol 10 (1): 25-34, 2009.16Sitzmann JV, Abrams R: Improved survival for hepatocellular cancer with combination surgery and multimodality treatment. Ann Surg 217 (2): 149-54, 1993.17Di Bisceglie AM, Rustgi VK, Hoofnagle JH, et al.: NIH conference. Hepatocellular carcinoma. Ann Intern Med 108 (3): 390-401, 1988.

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Advanced Adult Primary Liver Cancer

For patients with any T, N1, M1 disease.

There is no standard therapy for patients with advanced metastatic liver cancer. Such patients should be considered candidates for clinical trials exploring the usefulness of new biologicals or antitumor drugs (phase I and II studies) or combinations of existing drugs, radiosensitizers, and radiation therapy. Palliation may sometimes be achieved in such studies.

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with advanced adult primary liver cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

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Recurrent Adult Primary Liver Cancer

Note: Some citations in the text of this section are followed by a level of evidence. The PDQ editorial boards use a formal ranking system to help the reader judge the strength of evidence linked to the reported results of a therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence for more information.)

The prognosis for any treated primary liver cancer patient with progressing, recurring, or relapsing disease is poor. The question and selection of further treatment depends on many factors, including prior treatment, site of recurrence, presence of cirrhosis, and hepatic function as well as individual patient considerations. Re-resection should be considered when feasible, but most patients experience recurrence, typically in the liver.[1] When re-resection is not possible, treatment options for patients with recurrent hepatocellular cancer may include the use of transarterial oily chemoembolization (TOCE), percutaneous ethanol injection therapy (PEIT), chemotherapy, or liver transplantation.[2] At a single institution in Hong Kong, 244 consecutive patients treated with curative resection were followed for intrahepatic recurrence. Of the 244 patients followed, 139 patients did not develop intrahepatic recurrence and had 1-, 3-, and 5-year survival rates of 87%, 79%, and 74%, respectively. Of the 105 patients who developed subsequent intrahepatic recurrences, 11 patients were treated with re-resection and had 1-, 3-, and 5-year survival rates of 81%, 70%, and 69%, respectively; 71 patients were treated with TOCE and had 1-, 3-, and 5-year survival rates of 72%, 38%, and 20%, respectively; 6 patients were treated with PEIT and had 1-, 3-, 5-year survival rates of 67%, 22%, and 0%, respectively; the remaining 17 patients had either systemic chemotherapy or conservative treatment, and had no survivors at 3 years.[2][Level of evidence: 3iiA] Clinical trials are appropriate and should be considered whenever possible.

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with recurrent adult primary liver cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

1Shimada M, Takenaka K, Taguchi K, et al.: Prognostic factors after repeat hepatectomy for recurrent hepatocellular carcinoma. Ann Surg 227 (1): 80-5, 1998.2Poon RT, Fan ST, Lo CM, et al.: Intrahepatic recurrence after curative resection of hepatocellular carcinoma: long-term results of treatment and prognostic factors. Ann Surg 229 (2): 216-22, 1999.

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Changes to This Summary (02/23/2012)

The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.

General Information About Adult Primary Liver Cancer

Updated statistics with estimated new cases and deaths for 2012 (cited American Cancer Society as reference 1).

This summary is written and maintained by the PDQ Adult Treatment Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ NCI's Comprehensive Cancer Database pages.

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About This PDQ Summary

Purpose of This Summary

This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of adult primary liver cancer. It is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.

Reviewers and Updates

This summary is reviewed regularly and updated as necessary by the PDQ Adult Treatment Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).

Board members review recently published articles each month to determine whether an article should:

  • be discussed at a meeting,
  • be cited with text, or
  • replace or update an existing article that is already cited.

Changes to the summaries are made through a consensus process in which Board members evaluate the strength of the evidence in the published articles and determine how the article should be included in the summary.

The lead reviewers for Adult Primary Liver Cancer Treatment are:

  • Russell S. Berman, MD (New York University School of Medicine)
  • Giuseppe Giaccone, MD, PhD (National Cancer Institute)
  • Franco M. Muggia, MD (New York University Medical Center)

Any comments or questions about the summary content should be submitted to Cancer.gov through the Web site's Contact Form. Do not contact the individual Board Members with questions or comments about the summaries. Board members will not respond to individual inquiries.

Levels of Evidence

Some of the reference citations in this summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Adult Treatment Editorial Board uses a formal evidence ranking system in developing its level-of-evidence designations.

Permission to Use This Summary

PDQ is a registered trademark. Although the content of PDQ documents can be used freely as text, it cannot be identified as an NCI PDQ cancer information summary unless it is presented in its entirety and is regularly updated. However, an author would be permitted to write a sentence such as “NCI’s PDQ cancer information summary about breast cancer prevention states the risks succinctly: [include excerpt from the summary].”

The preferred citation for this PDQ summary is:

National Cancer Institute: PDQ® Adult Primary Liver Cancer Treatment. Bethesda, MD: National Cancer Institute. Date last modified <MM/DD/YYYY>. Available at: http://cancer.gov/cancertopics/pdq/treatment/adult-primary-liver/HealthProfessional. Accessed <MM/DD/YYYY>.

Images in this summary are used with permission of the author(s), artist, and/or publisher for use within the PDQ summaries only. Permission to use images outside the context of PDQ information must be obtained from the owner(s) and cannot be granted by the National Cancer Institute. Information about using the illustrations in this summary, along with many other cancer-related images, is available in Visuals Online, a collection of over 2,000 scientific images.

Disclaimer

Based on the strength of the available evidence, treatment options may be described as either “standard” or “under clinical evaluation.” These classifications should not be used as a basis for insurance reimbursement determinations. More information on insurance coverage is available on Cancer.gov on the Coping with Cancer: Financial, Insurance, and Legal Information page.

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More information about contacting us or receiving help with the Cancer.gov Web site can be found on our Contact Us for Help page. Questions can also be submitted to Cancer.gov through the Web site’s Contact Form.

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This information was last updated on 2012-02-23