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Table of Contents Purpose of This PDQ Summary
General Information
Cellular Classification
Stage Information
Localized Resectable Adult Primary Liver Cancer
Localized and Locally Advanced Unresectable Adult Primary Liver Cancer
Advanced Adult Primary Liver Cancer
Recurrent Adult Primary Liver Cancer
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Changes to This Summary (03/03/2008)
More Information
Purpose of This PDQ Summary
This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of adult primary liver cancer. This summary is reviewed regularly and updated as necessary by the PDQ Adult Treatment Editorial Board.
Information about the following is included in this summary:
- Prognostic factors.
- Cellular classification.
- Staging.
- Treatment options by cancer stage.
This summary 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.
Some of the reference citations in the 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. Based on the strength of the available evidence, treatment options are described as either “standard” or “under clinical evaluation.” These classifications should not be used as a basis for reimbursement determinations.
This summary is available in a patient version, written in less technical language, and in Spanish.
 Back to Top General Information
Note: A separate PDQ summary on Hepatocellular Cancer Screening is also available.
Note: Estimated new cases and deaths from liver and intrahepatic bile duct cancer in the United States in 2008:[1]
- New cases: 21,370.
- Deaths: 18,410.
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.)
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.
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.
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.[12,13] Other prognostic variables include performance status, liver
functions,[14] and the presence or absence of cirrhosis and its severity in
relation to the Child-Pugh classification.[15]
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.[16] Laparoscopic evaluation may detect
metastatic disease, bilobar disease, or inadequate liver remnant, and therefore
obviate the need for open surgical exploration.[17]
References
-
American Cancer Society.: Cancer Facts and Figures 2008. Atlanta, Ga: American Cancer Society, 2008. Also available online. Last accessed October 1, 2008.
-
El-Serag HB, Mason AC: Rising incidence of hepatocellular carcinoma in the United States. N Engl J Med 340 (10): 745-50, 1999.
[PUBMED Abstract]
-
Mor 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.
[PUBMED Abstract]
-
Klintmalm GB: Liver transplantation for hepatocellular carcinoma: a registry report of the impact of tumor characteristics on outcome. Ann Surg 228 (4): 479-90, 1998.
[PUBMED Abstract]
-
Jarnagin WR, Weber S, Tickoo SK, et al.: Combined hepatocellular and cholangiocarcinoma: demographic, clinical, and prognostic factors. Cancer 94 (7): 2040-6, 2002.
[PUBMED Abstract]
-
Blumberg 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.
[PUBMED Abstract]
-
Tsukuma 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.
[PUBMED Abstract]
-
Chiaramonte 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.
[PUBMED Abstract]
-
Tagger 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.
[PUBMED Abstract]
-
Yu 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.
[PUBMED Abstract]
-
Alpert ME, Hutt MS, Wogan GN, et al.: Association between aflatoxin content of food and hepatoma frequency in Uganda. Cancer 28 (1): 253-60, 1971.
[PUBMED Abstract]
-
Stillwagon 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.
[PUBMED Abstract]
-
Izumi 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.
[PUBMED Abstract]
-
Yamashita 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.
[PUBMED Abstract]
-
Nakakura EK, Choti MA: Management of hepatocellular carcinoma. Oncology (Huntingt) 14 (7): 1085-98; discussion 1098-102, 2000.
[PUBMED Abstract]
-
Karl RC, Morse SS, Halpert RD, et al.: Preoperative evaluation of patients for liver resection. Appropriate CT imaging. Ann Surg 217 (3): 226-32, 1993.
[PUBMED Abstract]
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Lo 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.
[PUBMED Abstract]
Back to Top Cellular Classification
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).
[Note: 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.
Back to Top Stage Information
The American Joint Committee on Cancer (AJCC) has designated TNM stages for
liver cancer as follows:[1]
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
[Note: 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
[Note: 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
Stage II
Stage IIIA
Stage IIIB
Stage IIIC
Stage IV
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.
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.[2-5] For other patients,
percutaneous ethanol injection, radiofrequency ablation, or chemoembolization may be options.[6]
Advanced Adult Primary Liver Cancer
(Any T, N1 or M1)
Advanced liver cancer is present in both lobes of the liveror
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]
References
-
Liver (including intrahepatic bile ducts). In: American Joint Committee on Cancer.: AJCC Cancer Staging Manual. 6th ed. New York, NY: Springer, 2002, pp 131-8.
-
Farmer DG, Rosove MH, Shaked A, et al.: Current treatment modalities for hepatocellular carcinoma. Ann Surg 219 (3): 236-47, 1994.
[PUBMED Abstract]
-
Ringe B, Wittekind C, Weimann A, et al.: Results of hepatic resection and transplantation for fibrolamellar carcinoma. Surg Gynecol Obstet 175 (4): 299-305, 1992.
[PUBMED Abstract]
-
Venook AP: Treatment of hepatocellular carcinoma: too many options? J Clin Oncol 12 (6): 1323-34, 1994.
[PUBMED Abstract]
-
Iwatsuki S, Starzl TE, Sheahan DG, et al.: Hepatic resection versus transplantation for hepatocellular carcinoma. Ann Surg 214 (3): 221-8; discussion 228-9, 1991.
[PUBMED Abstract]
-
Tanaka 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.
[PUBMED Abstract]
Back to Top 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.[4-7]
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 PDQ Cancer Clinical Trials Registry 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.
References
-
Fong 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.
[PUBMED Abstract]
-
Ohtsuka M, Ito H, Kimura F, et al.: Extended hepatic resection and outcomes in intrahepatic cholangiocarcinoma. J Hepatobiliary Pancreat Surg 10 (4): 259-64, 2003.
[PUBMED Abstract]
-
Karl 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.
[PUBMED Abstract]
-
Starzl TE, Koep LJ, Weil R 3rd, et al.: Right trisegmentectomy for hepatic neoplasms. Surg Gynecol Obstet 150 (2): 208-14, 1980.
[PUBMED Abstract]
-
Nagorney 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.
[PUBMED Abstract]
-
MacIntosh EL, Minuk GY: Hepatic resection in patients with cirrhosis and hepatocellular carcinoma. Surg Gynecol Obstet 174 (3): 245-54, 1992.
[PUBMED Abstract]
-
Hemming AW, Cattral MS, Reed AI, et al.: Liver transplantation for hepatocellular carcinoma. Ann Surg 233 (5): 652-9, 2001.
[PUBMED Abstract]
-
Pichlmayr 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.
[PUBMED Abstract]
-
Yamamoto J, Iwatsuki S, Kosuge T, et al.: Should hepatomas be treated with hepatic resection or transplantation? Cancer 86 (7): 1151-8, 1999.
[PUBMED Abstract]
-
Lau 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.
[PUBMED Abstract]
-
Takayama 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.
[PUBMED Abstract]
-
Nakajima Y, Ko S, Kanamura T, et al.: Repeat liver resection for hepatocellular carcinoma. J Am Coll Surg 192 (3): 339-44, 2001.
[PUBMED Abstract]
-
Neeleman N, Andersson R: Repeated liver resection for recurrent liver cancer. Br J Surg 83 (7): 893-901, 1996.
[PUBMED Abstract]
Back to Top 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
gelfoam powder or muscle fragments and chemotherapy, usually adriamycin. 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:
-
Radiofrequency ablation, chemoembolization, cryosurgery, or percutaneous ethanol injection: These techniques may be used in patients with small (<5 cm), localized, unresectable
tumors.[1,4-8]
-
Liver transplantation: For selected patients with localized unresectable hepatoma, particularly
patients with fibrolamellar hepatomas, liver transplantation may offer a
potentially curative treatment option.[9]
-
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,[10-12] as has regional chemotherapy with external-beam radiation
therapy.[13] Many patients are not candidates for these approaches, which
often require surgical intervention.
-
Systemic chemotherapy: Durable remissions have rarely been reported, and
no significant survival benefits have been conclusively demonstrated.
-
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.[14] However, the whole liver is not tolerant of large doses of radiation therapy.
-
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.[15]
Current Clinical Trials
Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry 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.
References
-
Zhou XD, Tang ZY: Cryotherapy for primary liver cancer. Semin Surg Oncol 14 (2): 171-4, 1998.
[PUBMED Abstract]
-
Lencioni 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.
[PUBMED Abstract]
-
A 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.
[PUBMED Abstract]
-
Livraghi T, Goldberg SN, Lazzaroni S, et al.: Small hepatocellular carcinoma: treatment with radio-frequency ablation versus ethanol injection. Radiology 210 (3): 655-61, 1999.
[PUBMED Abstract]
-
Tanaka 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.
[PUBMED Abstract]
-
Livraghi 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.
[PUBMED Abstract]
-
Livraghi 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.
[PUBMED Abstract]
-
Curley 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.
[PUBMED Abstract]
-
Hemming AW, Cattral MS, Reed AI, et al.: Liver transplantation for hepatocellular carcinoma. Ann Surg 233 (5): 652-9, 2001.
[PUBMED Abstract]
-
Ensminger 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.
[PUBMED Abstract]
-
Dakhil S, Ensminger W, Cho K, et al.: Improved regional selectivity of hepatic arterial BCNU with degradable microspheres. Cancer 50 (4): 631-5, 1982.
[PUBMED Abstract]
-
Choi 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.
[PUBMED Abstract]
-
Epstein B, Ettinger D, Leichner PK, et al.: Multimodality cisplatin treatment in nonresectable alpha-fetoprotein-positive hepatoma. Cancer 67 (4): 896-900, 1991.
[PUBMED Abstract]
-
Sitzmann JV, Abrams R: Improved survival for hepatocellular cancer with combination surgery and multimodality treatment. Ann Surg 217 (2): 149-54, 1993.
[PUBMED Abstract]
-
Di Bisceglie AM, Rustgi VK, Hoofnagle JH, et al.: NIH conference. Hepatocellular carcinoma. Ann Intern Med 108 (3): 390-401, 1988.
[PUBMED Abstract]
Back to Top 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 PDQ Cancer Clinical Trials Registry 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.
Back to Top 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 PDQ Cancer Clinical Trials Registry 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.
References
-
Shimada M, Takenaka K, Taguchi K, et al.: Prognostic factors after repeat hepatectomy for recurrent hepatocellular carcinoma. Ann Surg 227 (1): 80-5, 1998.
[PUBMED Abstract]
-
Poon 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.
[PUBMED Abstract]
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For more information, U.S. residents may call the National Cancer Institute's (NCI's) Cancer Information Service toll-free at 1-800-4-CANCER (1-800-422-6237) Monday through Friday from 9:00 a.m. to 4:30 p.m. Deaf and hard-of-hearing callers with TTY equipment may call 1-800-332-8615. The call is free and a trained Cancer Information Specialist is available to answer your questions.
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Find Publications
The NCI has booklets and other materials for patients, health professionals, and the public. These publications discuss types of cancer, methods of cancer treatment, coping with cancer, and clinical trials. Some publications provide information on tests for cancer, cancer causes and prevention, cancer statistics, and NCI research activities. NCI materials on these and other topics may be ordered online or printed directly from the NCI Publications Locator. These materials can also be ordered by telephone from the Cancer Information Service toll-free at 1-800-4-CANCER (1-800-422-6237), TTY at 1-800-332-8615.
Back to Top Changes to This Summary (03/03/2008)
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
Updated statistics with estimated new cases and deaths for 2008 (cited American Cancer Society).
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About PDQ
Additional PDQ Summaries
Important:
This information is intended mainly for use by doctors and other health care professionals. If you have questions about this topic, you can ask your doctor, or call the Cancer Information Service at 1-800-4-CANCER (1-800-422-6237).
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