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Adult Primary Liver Cancer Treatment (PDQ®)

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Stage Information for Adult Primary Liver Cancer

Prognostic modeling in hepatocellular carcinoma (HCC) is complex because cirrhosis is involved in as many as 80% of the cases. Tumor features and the factors related to functional hepatic reserve must be taken into account. The key prognostic factors are only partially known and vary at different stages of the disease.

More than ten classifications are used throughout the world, but no system is accepted worldwide. New classifications have been proposed in an effort to overcome the difficulties of having several staging systems.

This summary discusses the following three staging systems:

Barcelona Clinic Liver Cancer (BCLC) Staging System

Currently, the BCLC staging classification is the most accepted staging system for HCC and is useful in the staging of early tumors. Evidence from an American cohort has shown that BCLC staging offers better prognostic stratification power than other staging systems.[1]

The BCLC staging system attempts to overcome the limitations of previous staging systems by including variables related to the following:[2]

  • Tumor stage.
  • Functional status of the liver.
  • Physical status.
  • Cancer-related symptoms.

Five stages (0 and A through D) are identified based on the variables mentioned above. The BCLC staging system links each HCC stage to appropriate treatment modalities as follows:

  • Patients with early-stage HCC may benefit from curative therapies (i.e., liver transplantation, surgical resection, and radiofrequency ablation).
  • Patients with intermediate-stage or advanced-stage disease may benefit from palliative treatments (i.e., transcatheter arterial chemoembolization and sorafenib).
  • Patients with end-stage disease who have a very poor life expectancy are offered supportive care and palliation.

Okuda Staging System

The Okuda staging system has been extensively used in the past and includes variables related to tumor burden and liver function, such as bilirubin, albumin, and ascites. However, many significant prognostic tumor factors confirmed in both surgical and nonsurgical series (e.g., unifocal or multifocal, vascular invasion, portal venous thrombosis, or locoregional lymph node involvement) are not included.[3,4] As a result, Okuda staging is unable to stratify prognosis for early-stage cancers and mostly serves to recognize end-stage disease.

American Joint Committee on Cancer (AJCC) Staging System

Definitions of TNM

The TNM (tumor, node, and metastasis) classification for staging, proposed by the AJCC, is not widely used for liver cancer. Clinical use of TNM staging is limited because liver function is not considered. It is also difficult to use this system to select treatment options because TNM staging relies on detailed histopathological examination available only after tumor excision. TNM may be useful in prognostic prediction after liver resection.[5]

The AJCC has designated staging by TNM to define liver cancer as shown in tables 1, 2, 3, and 4.[5]

Table 1. Definitions of TNM Stage I
StageTNMDescription
T = primary tumor; N = regional lymph nodes; M = distant metastasis.
Reprinted with permission from AJCC: Liver. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual, 7th ed. New York, NY: Springer, 2010, pp 191-9.
IT1, N0, M0T1 = Solitary tumor without vascular invasion.
N0 = No regional lymph node metastasis.
M0 = No distant metastasis.
Table 2. Definitions of TNM Stage II
StageTNMDescription
T = primary tumor; N = regional lymph nodes; M = distant metastasis.
Reprinted with permission from AJCC: Liver. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual, 7th ed. New York, NY: Springer, 2010, pp 191-9.
IIT2, N0, M0T2 = Solitary tumor with vascular invasion or multiple tumors, none larger than 5 cm.
N0 = No regional lymph node metastasis.
M0 = No distant metastasis.
Table 3. Definitions of TNM Stage III
StageTNMDescription
T = primary tumor; N = regional lymph nodes; M = distant metastasis.
Reprinted with permission from AJCC: Liver. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual, 7th ed. New York, NY: Springer, 2010, pp 191-9.
IIIAT3a, N0, M0T3a = Multiple tumors larger than 5 cm.
N0 = No regional lymph node metastasis.
M0 = No distant metastasis.
IIIBT3b, N0, M0T3b = Single tumor or multiple tumors of any size involving a major branch of the portal vein or hepatic vein.
N0 = No regional lymph node metastasis.
M0 = No distant metastasis.
IIICT4, N0, M0T4 = Tumor(s) with direct invasion of adjacent organs other than the gallbladder or with perforation of visceral peritoneum.
N0 = No regional lymph node metastasis.
M0 = No distant metastasis.
Table 4. Definitions of TNM Stage IV
StageTNMDescription
T = primary tumor; N = regional lymph nodes; M = distant metastasis.
Reprinted with permission from AJCC: Liver. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual, 7th ed. New York, NY: Springer, 2010, pp 191-9.
IVAAny T, N1, M0TX = 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 larger than 5 cm.
T3a = Multiple tumors larger than 5 cm.
T3b = Single tumor or multiple tumors of any size involving a major branch of the portal vein or hepatic vein.
T4 = Tumor(s) with direct invasion of adjacent organs other than the gallbladder or with perforation of visceral peritoneum.
N1 = Regional lymph node metastasis.
M0 = No distant metastasis.
IVBAny T, Any N, M1TX = 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 larger than 5 cm.
T3a = Multiple tumors larger than 5 cm.
T3b = Single tumor or multiple tumors of any size involving a major branch of the portal vein or hepatic vein.
T4 = Tumor(s) with direct invasion of adjacent organs other than the gallbladder or with perforation of visceral peritoneum.
NX = Regional lymph nodes cannot be assessed.
N0 = No regional lymph node metastasis.
N1 = Regional lymph node metastasis.
M1 = Distant metastasis.

References

  1. Marrero JA, Fontana RJ, Barrat A, et al.: Prognosis of hepatocellular carcinoma: comparison of 7 staging systems in an American cohort. Hepatology 41 (4): 707-16, 2005. [PUBMED Abstract]
  2. Llovet JM, Brú C, Bruix J: Prognosis of hepatocellular carcinoma: the BCLC staging classification. Semin Liver Dis 19 (3): 329-38, 1999. [PUBMED Abstract]
  3. Poon RT, Ng IO, Fan ST, et al.: Clinicopathologic features of long-term survivors and disease-free survivors after resection of hepatocellular carcinoma: a study of a prospective cohort. J Clin Oncol 19 (12): 3037-44, 2001. [PUBMED Abstract]
  4. Pompili M, Rapaccini GL, Covino M, et al.: Prognostic factors for survival in patients with compensated cirrhosis and small hepatocellular carcinoma after percutaneous ethanol injection therapy. Cancer 92 (1): 126-35, 2001. [PUBMED Abstract]
  5. Liver. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 191-5.
  • Updated: January 20, 2015