Staging Strategy and Treatment for Patients With HCC

Liver transplant RFA/PEI

Curative treatments

TACE

Single

Increased Associateddiseases

Normal No Yes

Terminalstage

PST 0-2, Child-Pugh A-B

Multinodular, PST 0

Sorafenib

Portal pressure/bilirubin

3 nodules ≤ 3 cm

N1, M1, PST 1-2≤ 3 cm, PST 0

Intermediate stage

PST > 2,Child-Pugh C

Very early stageSingle < 2 cm

Early stageSingle or 3 nodules

Advanced stagePortal invasion,

PST 0, Child-Pugh A

Resection

Symptomatic

HCC

Palliative treatments

Forner A, Reig ME, de Lope CR, Bruix J. Current strategy for staging and treatment: the BCLC update and future prospects.Semin Liver Dis. 2010;30(1):61-74

Liver transplantation RFA/PEI

Curative treatments (30%); 5-yr survival: 40%-70%

TACE

Single

Increased Associateddiseases

Normal No Yes

Sorafenib

Portal pressure/bilirubin

3 nodules ≤ 3 cm

Resection Symptomatic (20%); survival <

3 mosRCTs (50%); 3-yr survival: 10%-40%

Terminalstage (D)

Okuda 1-2, PS 0-2, Child-Pugh A-B

Multinodular, PS 0 N1, M1, PS 1-2< 3 cm, PS 0

Intermediate stage (B)

Okuda 3, PS > 2,Child-Pugh C

Very early stage (0)Single < 2 cmCarcinoma in situ

Early stage (A)Single or 3 nodules

Advanced stage (C)Portal invasion,

PS 0, Child-Pugh AHCC

BCLC Staging and Treatment Strategy

Llovet JM, et al. Design and endpoints of clinical trials in hepatocellular carcinoma. Journal of the National Cancer Institute. 2008;100(10):698-711, by permission of Oxford University Press.

BCLC Staging System

Terminalstage (D)

Okuda 1-2, PS 0-2, Child-Pugh A-B

Multinodular, PS 0 N1, M1, PS 1-2< 3 cm, PS 0

Intermediate stage (B)

Okuda 3, PS > 2,Child-Pugh C

Very early stage (0)Single < 2 cmCarcinoma in situ

Early stage (A)Single or 3 nodules

Advanced stage (C)Portal invasion,

PS 0, Child-Pugh A

HCC

Llovet JM, et al. Design and endpoints of clinical trials in hepatocellular carcinoma. Journal of the National Cancer Institute. 2008;100(10):698-711, by permission of Oxford University Press.

Stage 0 Stage A-C Stage D

Liver Transplantation for HCC:Milan Criteria (Stage 1 and 2)

• 5-yr survival with transplantation: ~ 70%• 5-yr recurrent rates: < 15%

+Absence of macroscopic vascular invasion,

absence of extrahepatic spread

Single tumor, not > 5 cm Up to 3 tumors, none > 3 cm

Mazzaferro V, et al. N Engl J Med. 1996;334:693-699.Llovet JM. J Gastroenterol Hepatol. 2002;17(suppl 3):S428-S433.

Candidates for RFA/PEI

• Includes individuals who are not candidates for surgery

• Radiofrequency ablation generally preferred over percutaneous ethanol injection– Necrotic effect more predictable across tumor

sizes– Meta-analyses suggest survival benefit with

radiofrequency ablation vs percutaneous ethanol injection

Bruix J, et al. AASLD HCC guidelines. July 2010.

Liver transplantation RFA/PEI

Curative treatments (30%); 5-yr survival: 40%-70%

TACE

Single

Increased Associateddiseases

Normal No Yes

Sorafenib

Portal pressure/bilirubin

3 nodules ≤ 3 cm

Resection Symptomatic (20%); survival <

3 mosRCTs (50%); 3-yr survival: 10%-40%

Terminalstage (D)

Okuda 1-2, PS 0-2, Child-Pugh A-B

Multinodular, PS 0 N1, M1, PS 1-2< 3 cm, PS 0

Intermediate stage (B)

Okuda 3, PS > 2,Child-Pugh C

Very early stage (0)Single < 2 cmCarcinoma in situ

Early stage (A)Single or 3 nodules

Advanced stage (C)Portal invasion,

PS 0, Child-Pugh AHCC

Unresectable HCC

BCLC Staging and Treatment Strategy

Llovet JM, et al. Design and endpoints of clinical trials in hepatocellular carcinoma. Journal of the National Cancer Institute. 2008;100(10):698-711, by permission of Oxford University Press.

Llovet JM, et al. Hepatology. 2003;37:429-442.

Arterial Embolization for HCCMeta-analysis of 6 RCTs (2-Yr Survival)

Random Effects Model,OR (95% CI)

Author, Journal Yr Patients, n

Lin, Gastroenterology 1988 63

GETCH, NEJM 1995 96

Bruix, Hepatology 1998 80

Pelletier, J Hepatol 1998 73

Lo, Hepatology 2002 79

Llovet, Lancet 2002 112

Overall 503

Median survival: ~ 20 mos

0.01 0.1 0.5 1 2 10 100

Z = -2.3P = .017

Favors Treatment Favors Control

Contraindications to TACE

• Extrahepatic tumor spread• Lack of portal blood flow

– Portal vein thrombosis, portosystemic anastomoses or hepatofugal flow

• Advanced liver disease (Child-Pugh Class B or C)

• Clinical symptoms of end-stage cancer

Bruix J, et al. AASLD HCC guidelines. July 2010.

Liver transplantation RFA/PEI

Curative treatments (30%); 5-yr survival: 40%-70%

TACE

Single

Increased Associateddiseases

Normal No Yes

Sorafenib

Portal pressure/bilirubin

3 nodules ≤ 3 cm

Resection Symptomatic (20%); survival <

3 mosRCTs (50%); 3-yr survival: 10%-40%

Terminalstage (D)

Okuda 1-2, PS 0-2, Child-Pugh A-B

Multinodular, PS 0 N1, M1, PS 1-2< 3 cm, PS 0

Intermediate stage (B)

Okuda 3, PS > 2,Child-Pugh C

Very early stage (0)Single < 2 cmCarcinoma in situ

Early stage (A)Single or 3 nodules

Advanced stage (C)Portal invasion,

PS 0, Child-Pugh AHCC

BCLC Staging and Treatment Strategy

Llovet JM, et al. Design and endpoints of clinical trials in hepatocellular carcinoma. Journal of the National Cancer Institute. 2008;100(10):698-711, by permission of Oxford University Press.