Staging systems of hepatocellular carcinoma: A review of literature

Table 1 Comparison of classifications

Okuda staging system[13]
	Score
	0			1
Tumor size	≤ 50% of the liver			> 50% of the liver
Albumin (g/dL)	≥ 3			< 3
Bilirubin (mg/dL)	< 3			≥ 3
Ascites	Absent			Present
CLIP score[14]
	Score
	0		1		2
Tumour morphology	Uninodular and extension ≤ 50%		Multinodular and extension ≤ 50%		Massive or extension > 50%
Child–Pugh score	A		B		C
Alpha-fetoprotein (ng ⁄ mL)	< 400		≥ 400		-
Portal vein thrombosis	Absent		Present		-
GRETCH score[21]
	Score
	0	1	2	3
Karnofsky index	≥ 80%			< 80%
Bilirubin (μmol ⁄ L)	< 50			≥ 50
Alkaline phosphatase	< 2 X ULN		≥ 2 X ULN
Alpha-fetoprotein (μg⁄L)	< 35		≥ 35
Portal vein thrombosis	Absent	Present
BCLC[16]
	Stage
	0 (very early)	A (early)		B (intermediate)	C (advanced)		D (end stage)
ECOG Performance Status	0	0		0	1-2		3-4
Liver function	Child-Pugh A-B	Child-Pugh A-B		Child-Pugh A-B	Child-Pugh A-B		Child-Pugh C
Tumor stage	Single	Single or 3 nodules < 3 cm		Multinodular	Vascular invasion or extrahepatic spread		Any
CUPI[23]
VARIABLE		Weight
TNM stage	I and II	-3
	III	-1
	IV	0
Total Bilirubin (μmol ⁄ L)	< 34	0
	34-51	3
	≥ 52	4
Ascites		3
Alpha-fetoprotein > 500 ng/mL		2
Alkaline phosphatase > 200 IU/L		3
Asymptomatic disease on presentation		-4
JIS[24]
	Score
	0	1	2	3
Child-Pugh score	A	B	C
TNM stage by LCSGJ	I	II	III	IV
Tokyo[22]
	Score
	0	1	2
Albumin (g/dL)	> 3.5	2.8-3.5	< 2.8
Bilirubin (mg/dL)	< 1	1-2	> 2
Tumor size (cm)	< 2	2-5	> 5
Numbers of nodules	≤ 3	-	> 3
AJCC/UICC TNM staging system 7th ed[12]
Group	Description			Stage grouping
T1	Single tumor without vascular invasion			STAGE I	T1	N0	M0
T2	Single tumor with vascular invasion or multiple tumors, none > 5 cm			STAGE II	T2	N0	M0
T3a	Multiple tumors, any > 5 cm			STAGE IIIA	T3a	N0	M0
T3b	Single tumor or multiple tumors of any size involving a major branch of portal or hepatic vein(s)			STAGE IIIB	T3b	N0	M0
T4	Tumors with direct invasion of adjacent organs other than the gallbladder, or perforation of visceral peritoneum			STAGE IIIC	T4	N0	M0
N1	Regional lymph node metastasis			STAGE IVA	Any T	N1	M0
M1	Distant metastasis			STAGE IVB	Any T	Any N	M1

AJCC: American Joint Committee on Cancer; UICC: International Union Against Cancer; CLIP: Cancer of the Liver Italian Program; GRETCH: Groupe d’Etude et de Traitement du Carcinome Hépatocellulaire; BCLC: Barcelona clinic liver cancer; CUPI: Chinese University Prognostic Index for hepatocellular carcinoma; JIS: Japan Integrated Staging Score; TNM: Tumor Node Metastasis; ECOG: Eastern Cooperative Oncology Group; LCSGJ: Liver Cancer Study Group of Japan.

Table 2 Variables included in the main prognostic systems

Variables	Prognostic scores
	Okuda[13]	CLIP[14]	GRETCH[21]	BCLC[16]	CUPI[23]	JIS[24]	Tokyo[22]
Child-Pugh score		X		X		X
Ascites	X				X
Albumin	X						X
Total Bilirubin	X		X		X		X
Alkaline phosphatase			X		X
Alpha-fetoprotein		X	X		X
Tumor size	X	X		X			X
Numbers of nodules		X		X			X
TNM stage					X	X
Portal vein thrombosis		X	X	X
Metastasis				X
Portal hypertension				X
Presence of symptoms and/or General Status			X	X	X

CLIP: Cancer of the Liver Italian Program; GRETCH: Groupe d’Etude et de Traitement du Carcinome Hépatocellulaire; BCLC: Barcelona Clinic Liver Cancer; CUPI: Chinese University Prognostic Index; JIS: Japan Integrated Staging Score; TNM: Tumor Node Metastasis.

Table 3 Comparison of different hepatocellular carcinoma staging system in the literature

Ref.	Country	Year	Case number	Patient population	The best
Levy et al[58]	Canada	2002	257	All	CLIP
Kudo et al[59]	Japan	2004	4525	All	JIS
Cillo et al[41]	Italy	2004	187	All	BCLC
Grieco et al[39]	Italy	2005	268	Early to intermediate	BCLC
Marrero et al[34]	United States	2005	244	All	BCLC
Nanashima et al[60]	Japan	2005	210	Surgery	CLIP
Huang et al[61]	Taiwan	2005	599	Surgery	TNM
Toyoda et al[62]	Japan	2005	1508	All	JIS
Pascual et al[63]	Spain	2006	115	All	BCLC
Georgiades et al[42]	United States	2006	172	TACE	Child-Pugh
Cillo et al[64]	Italy	2006	195	All	BCLC
Nanashima et al[65]	Japan	2006	230	Surgery	Modified JIS
Kondo et al[66]	Japan	2007	235	Surgery	JIS
Seong et al[67]	South Korea	2007	305	Radiotherapy	TNM
Chen et al[40]	Taiwan	2007	382	Surgery	CLIP
Huo et al[68]	Taiwan	2007	430	All	CLIP
Cammà et al[37]	Italy	2008	406	All	CLIP
Guglielmi et al[69]	Italy	2008	112	RFA	BCLC
Collette et al[70]	French	2008	538	Advanced	CLIP
Lu et al[71]	China	2008	234	Surgery	TNM
Chung et al[72]	Japan	2008	290	All	JIS
Lin et al[38]	Taiwan	2009	3668	All	CLIP
Hsu et al[36]	Taiwan	2010	1713	All	CLIP
Op den Winkel et al[73]	German	2012	405	Non-surgical	CLIP
Kim et al[35]	South Korea	2012	1717	All	BCLC

CLIP: Cancer of the Liver Italian Program; GRETCH: Groupe d’Etude et de Traitement du Carcinome Hépatocellulaire; BCLC: Barcelona Clinic Liver Cancer; CUPI: Chinese University Prognostic Index; JIS: Japan Integrated Staging Score; TNM: Tumor Node Metastasis.