Staging of hepatocellular carcinoma

Abstract

Hepatocellular carcinoma (HCC) is the third leading cause of cancer deaths in the world. In contrast to other cancers, survival of patients with HCC is determined by the extent of the tumor in addition to underlying liver disease and its functional reserve. From risk factors to management, HCC reveals a considerable geographic and institutional variation throughout the world. Although many staging and/or scoring systems have been proposed, each prognostic system has several benefits and limitations on its own. Therefore, there is currently no globally accepted system for HCC due to the extreme heterogeneity of the disease. In this review, currently available staging systems for assessing the prognosis of HCC, their uses, limitations, and future prospects are revisited.

Keywords

Hepatocellular cancer / staging and scoring systems / risk factors / survival

References

[1] Bruix J.Prognostic prediction and treatment strategy in hepatocellular carcinoma.Hepatology2002;35:519-24

[2] Marrero JA,Barrat A,Conjeevaram HS,Lok AS.Prognosis of hepatocellular carcinoma: comparison of 7 staging systems in an American cohort.Hepatology2005;41:707-16

[3] Llovet JM,Bruix J.Prognosis of hepatocellular carcinoma: the BCLC staging classification.Semin Liver Dis1999;19:329-38

[4] Yau T,Yao TJ,Lo CM.Development of Hong Kong Liver Cancer staging system with treatment stratification for patients with hepatocellular carcinoma.Gastroenterology2014;146:1691-700.e3

[5] Edge S,Compton CC,Greene FL.AJCC cancer staging manual..7th ed.2010;New YorkSpringer

[6] Okuda K,Obata H,Okazaki N,Nakajima Y.Natural history of hepatocellular carcinoma and prognosis in relation to treatment.Study of 850 patients. Cancer1985;56:918-28

[7] A new prognostic system for hepatocellular carcinoma: a retrospective study of 435 patients: the Cancer of the Liver Italian Program (CLIP) investigators. Hepatology 1998;28:751-5

[8] Chevret S,Mathieu D,Beaugrand M.A new prognostic classification for predicting survival in patients with hepatocellular carcinoma.Groupe d'Etude et de Traitement du Carcinome Hepatocellulaire. J Hepatol1999;31:133-41

[9] Leung TW,Zee B,Lai PB,Lau JT,Johnson PJ.Construction of the Chinese University Prognostic Index for hepatocellular carcinoma and comparison with the TNM staging system, the Okuda staging system, and the Cancer of the Liver Italian Program staging system: a study based on 926 patients.Cancer2002;94:1760-9

[10] Kudo M,Osaki Y.Prognostic staging system for hepatocellular carcinoma (CLIP score): its value and limitations, and a proposal for a new staging system, the Japan Integrated Staging Score (JIS score).J Gastroenterol2003;38:207-15

[11] Tateishi R,Shiina S,Hasegawa K,Obi S,Koike Y,Makuuchi M.Proposal of a new prognostic model for hepatocellular carcinoma: an analysis of 403 patients.Gut2005;54:419-25 PMCID:PMC1774402

[12] Yang JD,Park KW,Kim B,Larson JJ,Therneau TM,Roberts LR.Model to estimate survival in ambulatory patients with hepatocellular carcinoma.Hepatology2012;56:614-21 PMCID:PMC3564594

[13] Schütte K,Link A.Current biomarkers for hepatocellular carcinoma: surveillance, diagnosis and prediction of prognosis.World J Hepatol2015;7:139-49 PMCID:PMC4342597

[14] Shouval D.HCC: what's the score?.Gut2002;50:749-50 PMCID:PMC1773236

[15] Cillo U,Vitale A,Burra P,D'Amico F,Boccagni P,Zanus G.The critical issue of hepatocellular carcinoma prognostic classification: which is the best tool available?.J Hepatol2004;40:124-31

[16] Rabe C,Schmitz V,Fimmers R,Caselmann WH.An independent evaluation of modern prognostic scores in a central European cohort of 120 patients with hepatocellular carcinoma.Eur J Gastroenterol Hepatol2003;15:1305-15

[17] Giannini E,Botta F,Malfatti F,Testa E,Chiarbonello B,Testa R.Prognosis of hepatocellular carcinoma in anti-HCV positive cirrhotic patients: a single-centre comparison amongst four different staging systems.J Intern Med2004;255:399-408

[18] Ueno S,Sako K,Hokotate H,Baba Y,Aikou T.Discrimination value of the new western prognostic system (CLIP score) for hepatocellular carcinoma in 662 Japanese patients.Hepatology2001;34:529-34

[19] Farinati F,Gianni S.How should patients with hepatocellular carcinoma be staged? Validation of a new staging system.Cancer2000;89:2266-73

[20] Prospective validation of the score: a new prognostic system for patients with cirrhosis and hepatocellular carcinoma CLIP.The Cancer of the Liver Italian Program (CLIP) Investigators.Hepatology2000;31:840-5

[21] Levy I.Staging of hepatocellular carcinoma: assessment of the CLIP, Okuda, and Child-Pugh staging systems in a cohort of 257 patients in Toronto.Gut2002;50:881-5 PMCID:PMC1773247

[22] Liu PH,Hsia CY,Su CW,Lee FY,Huo TI.Prognosis of hepatocellular carcinoma: assessment of eleven staging systems.J Hepatol2016;64:601-8

[23] Cillo U,Grigoletto F,Brolese A,Neri D,Srsen N,Ciarleglio FA,D'Amico DF.Prospective validation of the Barcelona Clinic Liver Cancer staging system.J Hepatol2006;44:723-31

[24] Marrero JA,Bronowicki JP.The challenge of prognosis and staging for hepatocellular carcinoma.Oncologist2010;15 Suppl 4:23-33

[25] Olthoff KM,Hübscher S.What is the best staging system for hepatocellular carcinoma in the setting of liver transplantation?.Liver Transpl2011;17 Suppl 2:S26-33

[26] Maida M,Cammà C.Staging systems of hepatocellular carcinoma: a review of literature.World J Gastroenterol2014;20:4141-50 PMCID:PMC3989950

[27] Subramaniam S,Ap Venook.A review of hepatocellular carcinoma (HCC) staging systems.Chin Clin Oncol2013;2:33

[28] Llovet JM,Bruix J.Hepatocellular carcinoma.Lancet2003;362:1907-17

[29] Cancer European Organisation for Research and Treatment of.EASLEORTC clinical practice guidelines: management of hepatocellular carcinoma.J Hepatol2012;56:908-43

[30] Bruix J.Management of hepatocellular carcinoma: an update.Hepatology2011;53:1020-2 PMCID:PMC3084991

[31] Oken MM,Tormey DC,Davis TE,Carbone PP.Toxicity and response criteria of the Eastern Cooperative Oncology Group.Am J Clin Oncol1982;5:649-55

[32] Forner A,Bruix J.Hepatocellular carcinoma.Lancet2012;379:1245-55

[33] Befeler AS.Hepatocellular carcinoma: diagnosis and treatment.Gastroenterology2002;122:1609-19

[34] Huitzil-Melendez FD,O'Reilly EM,Gansukh B,Abou-Alfa GK.Advanced hepatocellular carcinoma: which staging systems best predict prognosis?.J Clin Oncol2010;28:2889-95 PMCID:PMC3651603

[35] Zhang JF,Xie CY,Jin XH,Jiang FJ.Prognosis of unresectable hepatocellular carcinoma: comparison of seven staging systems (TNM, Okuda, BCLC, CLIP, CUPI, JIS, CIS) in a Chinese cohort.PLoS One2014;9:e88182 PMCID:PMC3946426

[36] Guglielmi A,Pachera S,Sandri M,Iacono C.Comparison of seven staging systems in cirrhotic patients with hepatocellular carcinoma in a cohort of patients who underwent radiofrequency ablation with complete response.Am J Gastroenterol2008;103:597-604

[37] Kim BK,Park JY,Ahn SH,Kim EH,Lee DY.Applicability of BCLC stage for prognostic stratification in comparison with other staging systems: single centre experience from long term clinical outcomes of 1717 treatment-naive patients with hepatocellular carcinoma.Liver Int2012;32:1120-7

[38] Bolondi L,Dufour JF,Mazzaferro V,Raoul JL.Heterogeneity of patients with intermediate (BCLC B) hepatocellular carcinoma: proposal for a subclassification to facilitate treatment decisions.Semin Liver Dis2012;32:348-59

[39] Chang WT,Chau GY,Lei HJ,Hsia CY,King KL.Hepatic resection can provide long-term survival of patients with non-early-stage hepatocellular carcinoma: extending the indication for resection?.Surgery2012;152:809-20

[40] Torzilli G,Kokudo N,Capussotti L,Vauthey JN,De Santibanes E,Morenghi E.A snapshot of the effective indications and results of surgery for hepatocellular carcinoma in tertiary referral centers: is it adherent to the EASL/AASLD recommendations? An observational study of the HCC East-West study group.Ann Surg2013;257:929-37

[41] Vitale A,Frigo AC,Farinati F,Volk M,Ciccarese F,Rapaccini GL,Caturelli E,Borzio F,Felder M,Sacco R,Missale G,Svegliati Baroni G,Cillo U.LI.CA) group. Survival benefit of liver resection for patients with hepatocellular carcinoma across different Barcelona Clinic Liver Cancer stages: a multicentre study; Italian Liver Cancer (ITA.LI.CA) group. J Hepatol2015;62:617-24

[42] Xu L,Chen MS,Zhang YJ,Lin XJ.Prognostic nomogram for patients with unresectable hepatocellular carcinoma after transcatheter arterial chemoembolization.J Hepatol2015;63:122-30

[43] Xue TC,Zhang L,Zhang BH.Transarterial chemoembolization for hepatocellular carcinoma with portal vein tumor thrombus: a meta-analysis.BMC Gastroenterol2013;13:60 PMCID:PMC3626696

[44] Center National Cancer.2014 KLCSG-NCC Korea practice guideline for the management of hepatocellular carcinoma.Gut Liver2015;9:267-317 PMCID:PMC4413964

[45] Hsu CY,Hsia CY,Su CW,Lee RC,Lee FY.Performance status in patients with hepatocellular carcinoma: determinants, prognostic impact, and ability to improve the Barcelona Clinic Liver Cancer system.Hepatology2013;57:112-9

[46] Huitzil-Melendez FD,O'Reilly EM,Gansukh B,Abou-Alfa GK.Advanced hepatocellular carcinoma: which staging systems best predict prognosis?.J Clin Oncol2010;28:2889-95 PMCID:PMC3651603

[47] Collette S,Paoletti X,Bouché O,Rougier P,Bedenne L.Prognosis of advanced hepatocellular carcinoma: comparison of three staging systems in two French clinical trials.Ann Oncol2008;19:1117-26

[48] Yau T,Chan P,Fan ST.A new prognostic score system in patients with advanced hepatocellular carcinoma not amendable to locoregional therapy: implication for patient selection in systemic therapy trials.Cancer2008;113:2742-51

[49] Marsh JW,Bonham CA.Is the pathologic TNM staging system for patients with hepatoma predictive of outcome?.Cancer2000;88:538-43

[50] Llovet JM,Fuster J,Garcia-Valdecasas JC,Franca A,Navasa M,Solé M,Vilana R,Visa J.Liver transplantation for small hepatocellular carcinoma: the tumor-node-metastasis classification does not have prognostic power.Hepatology1998;27:1572-7

[51] Vauthey JN,Esnaola NF,Belghiti J,Curley SA,Regimbeau JM,Cleary KR.Simplified staging for hepatocellular carcinoma.J Clin Oncol2002;20:1527-36

[52] Durand F,Belghiti J,Vilgrain V,Moutardier V,Valla D.Assessment of the benefits and risks of percutaneous biopsy before surgical resection of hepatocellular carcinoma.J Hepatol2001;35:254-58

[53] Chun YH,Park JY,Han KH,Kim BK,Kim KS,Ahn SH.Prognostic value of the 7th edition of the AJCC staging system as a clinical staging system in patients with hepatocellular carcinoma.Eur J Cancer2011;47:2568 75

[54] Makuuchi M,Belli G,Lau JW,Strasberg SM,Yamaoka Y.IHPBA concordant classification of primary liver cancer: working group report.J Hepatobiliary Pancreat Surg2003;10:26-30

[55] Kudo M,Haji S,Oka H,Kasugai H,Matsunaga T.Validation of a new prognostic staging system for hepatocellular carcinoma: the JIS score compared with the CLIP score.Hepatology2004;40:1396-405

[56] Toyoda H,Kiriyama S,Tanikawa M,Yamaguchi A,Kaneoka Y.Comparison of the usefulness of three staging systems for hepatocellular carcinoma (CLIP, BCLC, and JIS) in Japan.Am J Gastroenterol2005;100:1764-71

[57] Ikai I,Omata M,Nakanuma Y,Makuuchi M,Ichida T,Yamaoka Y.A modified Japan Integrated Stage score for prognostic assessment in patients with hepatocellular carcinoma.J Gastroenterol2006;41:884-92

[58] Kitai S,Minami Y,Chung H,Inoue T,Takahashi S,Haji S,Oka H,Kasugai H,Matsunaga T.A new prognostic staging system for hepatocellular carcinoma: value of the biomarker combined Japan integrated staging score.Intervirology2008;86-94

[59] Chan SL,Johnson PJ,Chan TC,Ma BB,Lai PB,Mok TS.Prospective validation of the Chinese University Prognostic Index and comparison with other staging systems for hepatocellular carcinoma in an Asian population.J Gastroenterol Hepatol2011;26:340-7

[60] Toyoda H,Osaki Y,Urano F,Matsunaga T.Staging hepatocellular carcinoma by a novel scoring system (BALAD score) based on serum markers.Clin Gastroenterol Hepatol2006;4:1528-36

[61] Fox R,Teng M,Tada T,Kumada T,Satomura S.Biomarker-based prognosis in hepatocellular carcinoma: validation and extension of the BALAD model.Br J Cancer2014;110:2090-8 PMCID:PMC3992496

[62] Chan SL,Johnson P,Tang N,Chan AW,Chan AT.Applicability of BALAD score in prognostication of hepatitis B-related hepatocellular carcinoma.J Gastroenterol Hepatol2015;30:1529-35

[63] Hsu CY,Hsia CY,Lin HC,Chiou YY,Lee PC,Lee SD.A new prognostic model for hepatocellular carcinoma based on total tumor volume: the Taipei Integrated Scoring System.J Hepatol2010;53:108-17

[64] Kamath PS.The model for end-stage liver disease (MELD).Hepatology2007;45:797-805

[65] Kim BH,Nam BH,Kim WR.Validation of a model to estimate survival in ambulatory patients with hepatocellular carcinoma: a single-centre cohort study.Liver Int2014;34:e317-23 PMCID:PMC4551431

[66] Adhoute X,Bronowicki JP.Usefulness of the HKLC vs.the BCLC staging system in a European HCC cohort. J Hepatol2015;62:492-3

[67] Kolly P,Sangro B,Candinas D.Assessment of the Hong Kong Liver Cancer Staging System in Europe.Liver Int2016;36:911-7

[68] Farinati F,Spolverato G,Huo TL,Frigo AC,Giannini EG,Piscaglia F,Di Marco M,Zoli M,Cabibbo G,Sacco R,Biasini E,Gasbarrini A,Virdone R,Trevisani F,ITA.LI.CA study group.Development and validation of a new prognostic system for patients with hepatocellular carcinoma.PLoS Med2016;13:e1002006 PMCID:PMC4846017

[69] Daniele B,Megna AS.Alpha-fetoprotein and ultrasonography screening for hepatocellular carcinoma.Gastroenterology2004;127:S108-12

[70] Yi X,Bao Y.Alpha-fetoprotein-L3 in hepatocellular carcinoma: a meta-analysis.Clin Chim Acta2013;425:212-20

[71] Zhao Y,Cui C,Liao F,Wu X.Significance of combined tests of serum golgi glycoprotein 73 and other biomarkers in diagnosis of small primary hepatocellular carcinoma.Cancer Biomark2015;15:677-83

[72] Caviglia GP,Petrini E,Rizzetto M.Highly sensitive alpha-fetoprotein, lens culinaris agglutinin-reactive fraction of alpha-fetoprotein and des-gamma-carboxyprothrombin for hepatocellular carcinoma detection.Hepatol Res2016;46:E130-5

[73] Poon RT,Tong CS,Ng IO.Prognostic significance of serum vascular endothelial growth factor and endostatin in patients with hepatocellular carcinoma.Br J Surg2004;91:1354-60

[74] Zhan P,Yu LK.Serum VEGF level is associated with the outcome of patients with hepatocellular carcinoma: a metaanalysis.Hepatobiliary Surg Nutr2013;2:209-15 PMCID:PMC3924686

[75] Yuen MF.Serological markers of liver cancer.Best Pract Res Clin Gastroenterol2005;19:91-9

[76] Hu J,Shen ZZ,Lu Q,Ding ZB,Zhou J.High expressions of vascular endothelial growth factor and platelet-derived endothelial cell growth factor predict poor prognosis in alpha-fetoprotein-negative hepatocellular carcinoma patients after curative resection.J Cancer Res Clin Oncol2009;135:1359-67