Staging systems for hepatocellular carcinoma: Current status and future perspectives

Table 1 Okuda

Stage	Ascites		Tumor size		Albumin		Bilirubin
	(+)	(-)	> 50%	< 50%	< 3 g/dL	> 3 g/dL	> 3 mg/dL
			(+)	(-)	(+)	(-)	(+)
I(mildly advanced)	(-)		(-)		(-)		(-)
II (moderately advanced)	One or two (+)
III (very advanced)	Three or four (+)

Table 2 Cancer of the Liver Italian Program

Variables	Scores
	0	1	2
Child-Pugh stage	A	B	C
Tumor morphology	uninodular and extension ≤ 50%	multinodular and extension ≤ 50%	massive or extension > 50%
AFP (ng/dL)	< 400	≥ 400
Portal vein thrombosis	-	+

AFP: Alpha-fetoprotein.

Table 3 GRETCH

Weight	0	1	2	3
Karnofsky index (%)	≥ 80			< 80
Serum bilirubin (μmol/L)	< 50			≥ 50
Serum ALP	< 2 × ULN		≥ 2 × ULN
Serum AFP (μg/L)	< 35		≥ 35
Portal obstruction (US)	-		+

AFP: Alpha-fetoprotein; ALP: Alkaline phosphatase; US: Ultrasound.

Table 4 Chines University Prognostic Index

Variable	Weight
TNM stage
Iand II	-3
IIIa and IIIb	-1
IVa and IVb	0
Asymptomatic disease on presentation	-4
Presence of ascites	3
AFP ≥ 500 ng/mL	2
Total bilirubin (μmol/L)
< 34	0
34-51	3
≥ 52	4
ALP ≥ 200 (IU/L)	3

≤ 1: Low risk; 2-7: Intermediate risk; ≥ 8: High risk. AFP: Alpha-fetoprotein; ALP: Alkaline phosphatase.

Table 5 American Joint Committee on Cancer /TNM 7^th edition

Primary tumor	Description
T1	Single tumor without vascular invasion
T2	Single tumor with vascular invasion or multiple tumors, none > 5 cm
T3a	Multiple tumors, any > 5 cm
T3b	Single tumor or multiple tumors of any size involving a major branch of the portal vein or hepatic vein
T4	Tumors with direct invasion of adjacent organs or perforation of visceral peritoneum
Stage grouping
StageI	T1	N0	M0
Stage II	T2	N0	M0
Stage III A	T3a	N0	M0
Stage III B	T3b	N0	M0
Stage III C	T4	N0	M0
Stage IV A	Any T	N1	M0
Stage IV B	Any T	Any N	M1

Table 6 Japan Integrated Staging Score

T factors I: Single; II: Size < 2 cm; III: No vascular invasion
T1	Fulfilling 3 factors
T2	Fulfilling 2 factors
T3	Fulfilling 1 factors
T4	Fulfilling 0 factors
StageI	T1N0M0
Stage II	T2N0M0
Stage III	T3N0M0
Stage IVA	T4N0M0 or any TN1M0
Stage IVB	Any TN0-1M1
Scores
Variables	0	1	2	3
Child-Pugh grade	A	B	C
TNM stage by LCSGJ	I	II	III	IV

LCSGJ: Liver Cancer Study Group of Japan.

Table 7 Stage, Liver damage and des-gamma-carboxy prothrombinscore

Parameter/score	0	1	2	3
Liver damage by LCSGJ	A	B	C
Stage by LCSGJ	I	II	III	IVA or IVB
DCP (mAU/mL)	< 400	≥ 400

LCSGJ: Liver Cancer Study Group of Japan; DCP: Des-gamma-carboxy prothrombin.

Table 8 Tokyo score

	Score
	0	1	2
Albumin (g/dL)	> 3.5	2.8-3.5	< 2.8
Total bilirubin (mg/dL)	< 1	1-2	> 2
Tumor size (cm)	< 2	2-5	> 5
Tumor number	≤ 3		> 3

Table 9 BALAD score: Scoring of remnant liver function

	Score
	0	1	2
Serum bilirubin (mg/dL)	< 1.0	1.0-2.0	> 2.0
Serum albumin (g/dL)	> 3.5	2.8-3.5	< 2.8
	0	1	2	3
Bilirubin-albumin score	A	B	C
Number of elevated tumor markers	0	1	2	3

A: 0-1 points; B: 2-3 points; C: 4 points.

Table 10 Memorial Sloan-Kettering Cancer Center nomogram: Prognostic factors

Age

Estimated blood loss

Margin

Satelites

Vascular invasion

Size

Log (alpha-fetoprotein)

Table 11 Advanced liver cancer prognostic system

Characteristics		Points
Ascites	Yes	2
	No	0
Abdominal pain	Yes	2
	No	0
Weight loss	Yes	2
	No	0
Child-Pugh grade	A	0
	B	2
	C	5
ALP (IU/L)	> 200	3
	≤ 200	0
Total bilirubin (mmol/L)	> 50	3
	33-50	1
	≤ 33	0
Urea (mmol/L)	> 8.9	2
	≤ 8.9	0
Portal vein thrombosis	Yes	3
	No	0
Tumor size	Diffuse	4
	> 5 cm	3
	≤ 5 cm	0
Lung metastases	Yes	3
	No	0
AFP (ng/mL)	> 400	4
	≤ 400	0
Prognosis	Score	3-mo survival rate
Good	0-2	> 0.81
	3-6	0.72-0.8
	7-8	0.66-0.69
Intermediate	9	0.63
	10-12	0.51-0.59
	13-14	0.42-0.47
	15	0.38
Poor	16	0.33
	17-19	0.21-0.29
	20-22	0.1-0.17
	≥ 23	< 0.1

AFP: Alpha-fetoprotein; ALP: Alkaline phosphatase.

Table 12 China Integrated Score

Variables	Scores
	0	1	2
TNM stage	≤ III	IVA	IVB
Child–Pugh grade	A	B	C
AFP (mg/L)	≤ 400	> 400
CIS score	0	1-2	3	4	5
	PEI or TACE	Herbs + TACE	TACE with herbs RCT	Chemotherapy	Symptomatic

CIS: China Integrated Score; TACE: Transarterial chemoembolization; AFP: Alpha-fetoprotein; PEI: Percutaneous ethanol injection; RCT: Randomized controlled trials.

Table 13 Taipei Integrated System

Variables	Scores
	0	1	2	3
Total tumor volume (cm3)	< 50	50-250	250-500	> 500
Child-Pugh grade	A	B	C
AFP (ng/mL)	≤ 400	> 400

AFP: Alpha-fetoprotein.

Table 14 Eastern stage

Variables	Score
	0	1
Macroscopic vascular invasion	-	+
Tumor number	Solitary	Multiple
PS	0	1-2
Microscopic vascular invasion	-	+
Extrahepatic spread	-	+
Maximum tumor size (cm)	≤ 5	> 5
Albumin (g/L)	≥ 35	< 35
AST (U/L)	≤ 40	> 40
Total bilirubin (μmol/L)	≤ 17	> 17
Presence of cirrhosis	-	+
	Cumulative score
Stage I	0-1
Stage II	2-3
Stage III	4-5
Stage IV	6-7
Stage V	8-10

AST: Aspartate transaminase.

Table 15 Portal vein tumor thrombus classification

Types
TypeI0: Tumor thrombus formation found under microscopy
TypeI: Tumor thrombi involving segmental branches of portal vein or above
Type II: Tumor thrombi involving right/left portal vein
Type III: Tumor thrombi involving the main portal vein trunk
Type IV: Tumor thrombi involving the superior mesenteric artery

Table 16 A prognostic model for hepatocellular carcinoma patients within the Milan criteria undergoing non‐transplant therapies

Variables	Scores
	0	1	2
Total bilirubin (mg/dL)	< 1.5	≥ 1.5
AFP (ng/mL)	< 100	≥ 100
Ascites	-	Mild	Moderate to severe

AFP: Alpha-fetoprotein.

Table 17 Model to Estimate Survival in Ambulatory hepatocellular carcinoma patients score

MESIAH score
= 0.232 * (age in decades)
+ 0.099 * (MELD)
- 0.391 * (serum albumin level)
+ 0.290 * (tumor size)
+ 0.153 * (tumor number)
+ 1.122 * (vascular invasion)
+ 1.130 * (extrahepatic metastasis)
+ 0.082 * (serum AFP level)
+1

AFP: Alpha-fetoprotein. MESIAH: Model to Estimate Survival in Ambulatory HCC patients score; HCC: Hepatocellular carcinoma.

Table 18 Alpha-fetoprotein staging

AFP (ng/mL)	Stage
< 10	N (normal)
10-150	A
150-500	B
> 500	C

AFP: Alpha-fetoprotein.

Table 19 Hepatoma arterial-embolisation score

Variables	Points
Albumin < 36 g/dL	1
AFP > 400 ng/mL	1
Total bilirubin > 17 μmol/L	1
Maximum tumor diameter > 7 cm	1

AFP: Alpha-fetoprotein.

Table 20 Barcelona Clinic Liver Cancer B subclassification

Sub-Stage	B1	B2	B3	B4
Child-Pugh score	5-6-7	5-6	7	8-9 (with severe/refractory ascites and/or jaundice)
Beyond Milan and within Ut-7	In	Out	Out	Any
ECOG (tumor related) PS	0	0	0	0-1
Portal vein thrombosis	-	-	-	-
1st option Alternative	TACE Liver transplantaion TACE + ablation	TACE or TARE sorafenib	Research trials TACE sorafenib	BSC Liver transplantaion (only if Up-to-7 IN and PS0)

TACE: Transarterial chemoembolization; TARE: Transarterial radioembolization; BSC: Best supportive care.