Hepatocellular Carcinoma Staging
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Staging systems for hepatocellular carcinoma (HCC) have not been universally adopted. One system implemented is the American Joint Committee on Cancer (AJCC) tumor/node/metastasis (TNM) classification system. The TNM classification system takes into account tumor characteristics including size, number, and vascular invasion, as well as lymph node involvement and metastatic disease. [1, 2]
Table 1. TNM Classification for Hepatocellular Carcinoma (Open Table in a new window)
Primary tumor (T)
TX
Primary tumor cannot be assessed
T0
No evidence of primary tumor
T1
Solitary tumor 2 cm without vascular invasion
T1a
Solitary tumor <2 cm
T1b
Solitary tumor >2 cm without vascular invasion
T2
Solitary tumor >2 cm with vascular invasion; or multiple tumors, none >5 cm
T3
Multiple tumors, at least one of which is >5 cm
T4
Single tumor or tumors of any size involving a major branch of the portal vein or hepatic vein, or tumor(s) with direct invasion of adjacent organs other than the gallbladder or with perforation of visceral peritoneum
Regional lymph nodes (N)
NX
Regional lymph nodes cannot be assessed
N0
No regional lymph node metastasis
N1
Regional lymph node metastasis
Distant metastasis (M)
M0
No distant metastasis
M1
Distant metastasis
Table 2. Anatomic stage/prognostic groups (Open Table in a new window)
Stage
T
N
M
IA
T1a
N0
M0
IB
T1b
N0
M0
II
T2
N0
M0
IIIA
T3
N0
M0
IIIB
T4
N0
M0
IVA
Any T
N1
M0
IVB
Any T
Any N
M1
Table 3. Histologic grade (Open Table in a new window)
Histologic grade (G)
GX
Grade cannot be accessed
G1
Well differentiated
G2
Moderately differentiated
G3
Poorly differentiated
G4
Undifferentiated
In addition to the TNM staging for HCC, other systems have been proposed to help guide therapeutic strategies. One of these validated systems is the Barcelona-Clinic Liver Cancer staging system (BCLC). The BCLC system stratifies HCC patients based on tumor size, extent, liver function, and performance status. The BCLC staging system is thought to be better than other staging systems for determining prognosis, given the inclusion of liver function and performance status. [3, 4]
Table 4. Barcelona-Clinic Liver Cancer staging system (Open Table in a new window)
Stage
Performance Status
Tumor Stage
Okuda Stage
Liver function
A: Early HCC
A1
0
Single, < 5 cm
I
No portal hypertension, normal bilirubin
A2
0
Single, < 5 cm
I
Portal hypertension, normal bilirubin
A3
0
Single, < 5 cm
I
Portal hypertension, abnormal bilirubin
A4
0
3 tumors, < 3 cm
I-II
Child-Pugh A-B
Stage B: Intermediate HCC
0
Large, multinodular
I-II
Child-Pugh A-B
Stage C: Advanced HCC
1-2
Vascular invasion or extrahepatic spread
I-II
Child-Pugh A-B
Stage D: End-Stage HCC
3-4
Any
I-II
Child-Pugh C
Stage A and B: All criteria need to be fulfilled
Stage C: At least one of the following criteria needs to be filled: performance status 1-2 or vascular invasion/extrahepatic spread.
Stage D: At least one of the following criteria needs to be filled: performance status 3-4 or Okuda Stage III/Child Pugh C.
Cirrhosis is an important component of HCC staging. Cirrhosis is not only an independent predictor of survival but also guides management decisions and determines candidacy for different therapies. The Child-Pugh score can be used to classify the prognosis based on the degree of cirrhosis and therefore can help in determining operative risk
Another consideration in determining stage and prognosis in patients with HCC is the degree of liver fibrosis. There are many different scoring systems used to determine the degree of liver fibrosis. With one such scoring system, the Ishak fibrosis staging system, stages 1 through 5 had no direct correlation with survival, however, stage 6 was associated with poor overall survival [5]
Table 5. Ishak fibrosis score (Open Table in a new window)
Architectural Change
Score
No fibrosis
0
Fibrous expansion of some portal areas, with or without short fibrous septa
1
Fibrous expansion of most portal areas, , with or without short fibrous septa
2
Fibrous expansion of most portal areas, with occasional portal-to-portal bridging
3
Fibrous expansion of portal areas with marked bridging as well as portal-central
4
Marked bridging (portal-to-portal and/or portal-central) with occasional nodule (incomplete cirrhosis)
5
Cirrhosis, probable or definite
6
[Guideline] National Comprehensive Cancer Network. NCCN Hepatobiliary Cancers Clinical Practice Guidelines in Oncology. Available at http://www.nccn.org/professionals/physician_gls/pdf/hepatobiliary.pdf. Version 1.2018 — February 14, 2018; Accessed: April 2, 2018.
American Joint Committee on Cancer. Liver. Amin MB, Edge S, Greene F, Byrd DR, Brookland RK, et al, eds. AJCC Cancer Staging Manual. 8th edition. New York: Springer; 2016.
Llovet JM, Brú C, Bruix J. Prognosis of hepatocellular carcinoma: the BCLC staging classification. Semin Liver Dis. 1999. 19 (3):329-38. [Medline].
Subramaniam S, Kelley RK, Venook AP. A review of hepatocellular carcinoma (HCC) staging systems. Chin Clin Oncol. 2013 Dec. 2 (4):33. [Medline]. [Full Text].
Wang Q, Fiel MI, Blank S, Luan W, Kadri H, Kim KW, et al. Impact of liver fibrosis on prognosis following liver resection for hepatitis B-associated hepatocellular carcinoma. Br J Cancer. 2013 Aug 6. 109 (3):573-81. [Medline]. [Full Text].
Primary tumor (T)
TX
Primary tumor cannot be assessed
T0
No evidence of primary tumor
T1
Solitary tumor 2 cm without vascular invasion
T1a
Solitary tumor <2 cm
T1b
Solitary tumor >2 cm without vascular invasion
T2
Solitary tumor >2 cm with vascular invasion; or multiple tumors, none >5 cm
T3
Multiple tumors, at least one of which is >5 cm
T4
Single tumor or tumors of any size involving a major branch of the portal vein or hepatic vein, or tumor(s) with direct invasion of adjacent organs other than the gallbladder or with perforation of visceral peritoneum
Regional lymph nodes (N)
NX
Regional lymph nodes cannot be assessed
N0
No regional lymph node metastasis
N1
Regional lymph node metastasis
Distant metastasis (M)
M0
No distant metastasis
M1
Distant metastasis
Stage
T
N
M
IA
T1a
N0
M0
IB
T1b
N0
M0
II
T2
N0
M0
IIIA
T3
N0
M0
IIIB
T4
N0
M0
IVA
Any T
N1
M0
IVB
Any T
Any N
M1
Histologic grade (G)
GX
Grade cannot be accessed
G1
Well differentiated
G2
Moderately differentiated
G3
Poorly differentiated
G4
Undifferentiated
Stage
Performance Status
Tumor Stage
Okuda Stage
Liver function
A: Early HCC
A1
0
Single, < 5 cm
I
No portal hypertension, normal bilirubin
A2
0
Single, < 5 cm
I
Portal hypertension, normal bilirubin
A3
0
Single, < 5 cm
I
Portal hypertension, abnormal bilirubin
A4
0
3 tumors, < 3 cm
I-II
Child-Pugh A-B
Stage B: Intermediate HCC
0
Large, multinodular
I-II
Child-Pugh A-B
Stage C: Advanced HCC
1-2
Vascular invasion or extrahepatic spread
I-II
Child-Pugh A-B
Stage D: End-Stage HCC
3-4
Any
I-II
Child-Pugh C
Stage A and B: All criteria need to be fulfilled
Stage C: At least one of the following criteria needs to be filled: performance status 1-2 or vascular invasion/extrahepatic spread.
Stage D: At least one of the following criteria needs to be filled: performance status 3-4 or Okuda Stage III/Child Pugh C.
Architectural Change
Score
No fibrosis
0
Fibrous expansion of some portal areas, with or without short fibrous septa
1
Fibrous expansion of most portal areas, , with or without short fibrous septa
2
Fibrous expansion of most portal areas, with occasional portal-to-portal bridging
3
Fibrous expansion of portal areas with marked bridging as well as portal-central
4
Marked bridging (portal-to-portal and/or portal-central) with occasional nodule (incomplete cirrhosis)
5
Cirrhosis, probable or definite
6
Anand D Patel, MD Hematologist/Oncologist, Ascension Wisconsin
Anand D Patel, MD is a member of the following medical societies: American College of Physicians, American Medical Association, Student National Medical Association
Disclosure: Nothing to disclose.
Amber Lynn Sobuto, DO Fellow, Department of Hematology and Medical Oncology, Lankenau Medical Center
Amber Lynn Sobuto, DO is a member of the following medical societies: American College of Physicians, American Osteopathic Association, American Society of Clinical Oncology, American Society of Hematology, American Thoracic Society
Disclosure: Nothing to disclose.
Erik L Zeger, MD Consulting Staff, Main Line Oncology Hematology Associates
Erik L Zeger, MD is a member of the following medical societies: Alpha Omega Alpha, American Association for Cancer Research, American Society of Hematology
Disclosure: Nothing to disclose.
Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference
Disclosure: Nothing to disclose.
Christopher D Braden, DO Hematologist/Oncologist, Chancellor Center for Oncology at Deaconess Hospital; Medical Director, Deaconess Hospital Outpatient Infusion Centers; Chairman, Deaconess Hospital Cancer Committee
Christopher D Braden, DO is a member of the following medical societies: American Society of Clinical Oncology, American Society of Hematology
Disclosure: Nothing to disclose.
N Joseph Espat, MD, MS, FACS Harold J Wanebo Professor of Surgery, Assistant Dean of Clinical Affairs, Boston University School of Medicine; Chairman, Department of Surgery, Director, Adele R Decof Cancer Center, Roger Williams Medical Center
N Joseph Espat, MD, MS, FACS is a member of the following medical societies: Alpha Omega Alpha, American Association for Cancer Research, American College of Surgeons, American Medical Association, American Society for Parenteral and Enteral Nutrition, American Society of Clinical Oncology, Americas Hepato-Pancreato-Biliary Association, Association for Academic Surgery, Central Surgical Association, Chicago Medical Society, International Hepato-Pancreato-Biliary Association, Pancreas Club, Sigma Xi, Society for Leukocyte Biology, Society for Surgery of the Alimentary Tract, Society of American Gastrointestinal and Endoscopic Surgeons, Society of Surgical Oncology, Society of University Surgeons, Southeastern Surgical Congress, Southern Medical Association, Surgical Infection Society
Disclosure: Nothing to disclose.
Terence D Rhodes, MD, PhD Medical Oncologist, Intermountain Medical Group
Terence D Rhodes, MD, PhD is a member of the following medical societies: American Association for Cancer Research, American Society of Clinical Oncology
Disclosure: Nothing to disclose.
Hepatocellular Carcinoma Staging
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