Stage Information for Adult Primary Liver Cancer

TNM Definitions
AJCC Stage Groupings
Localized Resectable Adult Primary Liver Cancer
Localized and Locally Advanced Unresectable Adult Primary Liver Cancer
Advanced 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

 [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

• 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.[2-4] 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]

References

1. Mazzaferro 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.  [PUBMED Abstract]
   
   
2. Llovet JM, Burroughs A, Bruix J: Hepatocellular carcinoma. Lancet 362 (9399): 1907-17, 2003.  [PUBMED Abstract]
   
   
3. Bruix J, Sherman M; Practice Guidelines Committee, American Association for the Study of Liver Diseases.: Management of hepatocellular carcinoma. Hepatology 42 (5): 1208-36, 2005.  [PUBMED Abstract]
   
   
4. Bruix 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.  [PUBMED Abstract]
   
   
5. Pawlik 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.  [PUBMED Abstract]
   
   
6. 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]