A new staging system for resectable hepatocellular carcinoma: comparison with six existing staging systems in a large Chinese cohort

  • Tian Yang
  • Jin Zhang
  • Jun-Hua Lu
  • Li-Qun Yang
  • Guang-Shun Yang
  • Meng-Chao Wu
  • Wei-Feng Yu
Original Paper



Surgical resection remains the gold standard for hepatocellular carcinoma (HCC). Although various staging systems have been developed in recent years, the best tool for staging of HCC remains controversial. The aims of this study were to establish a new staging for patients with HCC undergoing surgical resection and to indentify whether this staging is superior to other staging systems in predicting survival of resectable HCC.


The subjects of this retrospective study were 958 consecutive HCC patients who underwent surgical resection between 2000 and 2006. Predictors of survival were identified using the Kaplan–Meier method and the Cox model. The disease state was staged by our proposed Eastern staging system by integrating independent risk predictors, as well as six existing staging systems. The accuracy of prediction of 1-, 3-, and 5-year mortality for each system was evaluated by the area under the receiver operating characteristic curve (AUC).


Macroscopic vascular invasion, multiple tumors, performance status 1–2, microscopic vascular invasion, extrahepatic spread, tumor size > 5 cm, albumin < 35 g/L, aspartate aminotransferase > 40 U/L, total bilirubin > 17 μmol/L, and presence of cirrhosis were identified as independent risk factors of survival after resection by multivariate analysis. The comparison of the results of the different staging systems showed that our Eastern staging had the best homogeneity (likelihood ratio χ2 test 543.51, P < 0.001), monotonicity of gradients (linear trend χ2 test 414.97, P < 0.001), and discriminatory ability (the highest AUCs for 1-, 3-, and 5-year mortality).


Compared with other existing staging systems, our proposed Eastern staging system shows a superior predictive ability in a Chinese cohort of patients with resectable HCC, and it can give important prognostic information after surgery.


Hepatocellular carcinoma Staging Surgical resection 



Hepatocellular carcinoma


Hepatitis B virus


American Joint Committee on Cancer Staging


Tumor node metastasis


Cancer of Liver Italian Program


Barcelona Clinic Liver Cancer


Chinese University Prognostic Index


Japanese Integrated System


Eastern Cooperative Oncology Group


Percutaneous ethanol injection




Transarterial chemoembolization


Receiver operating characteristic


Area under curve


Hepatitis C virus


Portal vein thrombosis


Total bilirubin




Aspartate aminotransferase


Likelihood ratio


  1. Bruix J, Llovet JM (2009) Major achievements in hepatocellular carcinoma. Lancet 373:614–616PubMedCrossRefGoogle Scholar
  2. Bruix J, Sherman M (2005) Management of hepatocellular carcinoma. Hepatology 42:1208–1236PubMedCrossRefGoogle Scholar
  3. Bruix J, Sherman M, Llovet JM, Beaugrand M, Lencioni R, Burroughs AK, Christensen E, Pagliaro L, Colombo M, Rodes J (2001) Clinical management of hepatocellular carcinoma. Conclusions of the Barcelona-2000 EASL conference. European Association for the Study of the Liver. J Hepatol 35:421–430PubMedCrossRefGoogle Scholar
  4. Chen MF, Tsai HP, Jeng LB, Lee WC, Yeh CN, Yu MC, Hung CM (2003) Prognostic factors after resection for hepatocellular carcinoma in noncirrhotic livers: univariate and multivariate analysis. World J Surg 27:443–447PubMedCrossRefGoogle Scholar
  5. Chen TW, Chu CM, Yu JC, Chen CJ, Chan DC, Liu YC, Hsieh CB (2007) Comparison of clinical staging systems in predicting survival of hepatocellular carcinoma patients receiving major or minor hepatectomy. Eur J Surg Oncol 33:480–487PubMedCrossRefGoogle Scholar
  6. Chen CH, Hu FC, Huang GT, Lee PH, Tsang YM, Cheng AL, Chen DS, Wang JD, Sheu JC (2009) Applicability of staging systems for patients with hepatocellular carcinoma is dependent on treatment method–analysis of 2010 Taiwanese patients. Eur J Cancer 45:1630–1639PubMedCrossRefGoogle Scholar
  7. Cillo U, Bassanello M, Vitale A, Grigoletto FA, Burra P, Fagiuoli S, D’Amico F, Ciarleglio FA, Boccagni P, Brolese A, Zanus G, D’Amico DF (2004) The critical issue of hepatocellular carcinoma prognostic classification: which is the best tool available. J Hepatol 40:124–131PubMedCrossRefGoogle Scholar
  8. Cillo U, Vitale A, Grigoletto F, Farinati F, Brolese A, Zanus G, Neri D, Boccagni P, Srsen N, D’Amico F, Ciarleglio FA, Bridda A, D’Amico DF (2006) Prospective validation of the Barcelona Clinic Liver Cancer staging system. J Hepatol 44:723–731PubMedCrossRefGoogle Scholar
  9. Feinstein AR (1972) Clinical biostatistics. XVI. The process of prognostic stratification. 2. Clin Pharmacol Ther 13:609–624PubMedGoogle Scholar
  10. Grazi GL, Cescon M, Ravaioli M, Ercolani G, Gardini A, Del GM, Vetrone G, Cavallari A (2003) Liver resection for hepatocellular carcinoma in cirrhotics and noncirrhotics. Evaluation of clinicopathologic features and comparison of risk factors for long-term survival and tumour recurrence in a single centre. Aliment Pharmacol Ther 17(Suppl 2):119–129PubMedCrossRefGoogle Scholar
  11. Greene FL, Page DL, Fleming ID, Fritz AG, Balch CM, Haller DG, Morrow M (2002) AJCC Cancer staging manual, 6th edn. Springer, New YorkCrossRefGoogle Scholar
  12. Hanley JA, McNeil BJ (1982) The meaning and use of the area under a receiver operating characteristic (ROC) curve. Radiology 143:29–36PubMedGoogle Scholar
  13. Hanley JA, McNeil BJ (1983) A method of comparing the areas under receiver operating characteristic curves derived from the same cases. Radiology 148:839–843PubMedGoogle Scholar
  14. Hosmer DW, Hosmer T, Le CS, Lemeshow S (1997) A comparison of goodness-of-fit tests for the logistic regression model. Stat Med 16:965–980PubMedCrossRefGoogle Scholar
  15. Investigators TC (1998) A new prognostic system for hepatocellular carcinoma: a retrospective study of 435 patients: the Cancer of the Liver Italian Program (CLIP) investigators. Hepatology 28:751–755Google Scholar
  16. Investigators TC (2000) Prospective validation of the CLIP score: a new prognostic system for patients with cirrhosis and hepatocellular carcinoma. The Cancer of the Liver Italian Program (CLIP) Investigators. Hepatology 31:840–845CrossRefGoogle Scholar
  17. Kudo M, Chung H, Osaki Y (2003) 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 Gastroenterol 38:207–215PubMedCrossRefGoogle Scholar
  18. Lei HJ, Chau GY, Lui WY, Tsay SH, King KL, Loong CC, Wu CW (2006) Prognostic value and clinical relevance of the 6th Edition 2002 American Joint Committee on Cancer staging system in patients with resectable hepatocellular carcinoma. J Am Coll Surg 203:426–435PubMedCrossRefGoogle Scholar
  19. Leung TW, Tang AM, Zee B, Lau WY, Lai PB, Leung KL, Lau JT, Yu SC, Johnson PJ (2002) 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. Cancer 94:1760–1769PubMedCrossRefGoogle Scholar
  20. Levy I, Sherman M (2002) Staging of hepatocellular carcinoma: assessment of the CLIP, Okuda, and Child-Pugh staging systems in a cohort of 257 patients in Toronto. Gut 50:881–885PubMedCrossRefGoogle Scholar
  21. Llovet JM, Bru C, Bruix J (1999a) Prognosis of hepatocellular carcinoma: the BCLC staging classification. Semin Liver Dis 19:329–338PubMedCrossRefGoogle Scholar
  22. Llovet JM, Bustamante J, Castells A, Vilana R, Ayuso MC, Sala M, Bru C, Rodes J, Bruix J (1999b) Natural history of untreated nonsurgical hepatocellular carcinoma: rationale for the design and evaluation of therapeutic trials. Hepatology 29:62–67PubMedCrossRefGoogle Scholar
  23. Llovet JM, Di BAM, Bruix J, Kramer BS, Lencioni R, Zhu AX, Sherman M, Schwartz M, Lotze M, Talwalkar J, Gores GJ (2008a) Design and endpoints of clinical trials in hepatocellular carcinoma. J Natl Cancer Inst 100:698–711PubMedCrossRefGoogle Scholar
  24. Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF, de Oliveira AC, Santoro A, Raoul JL, Forner A, Schwartz M, Porta C, Zeuzem S, Bolondi L, Greten TF, Galle PR, Seitz JF, Borbath I, Haussinger D, Giannaris T, Shan M, Moscovici M, Voliotis D, Bruix J (2008b) Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 359:378–390PubMedCrossRefGoogle Scholar
  25. Luo KZ, Itamoto T, Amano H, Oshita A, Ushitora Y, Tanimoto Y, Ohdan H, Tashiro H, Asahara T (2008) Comparative study of the Japan Integrated Stage (JIS) and modified JIS score as a predictor of survival after hepatectomy for hepatocellular carcinoma. J Gastroenterol 43:369–377PubMedCrossRefGoogle Scholar
  26. Markovic S, Gadzijev E, Stabuc B, Croce LS, Masutti F, Surlan M, Berden P, Brencic E, Visnar-Perovic A, Sasso F, Ferlan-Marolt V, Mucelli FP, Cesar R, Sponza M, Tiribelli C (1998) Treatment options in Western hepatocellular carcinoma: a prospective study of 224 patients. J Hepatol 29:650–659PubMedCrossRefGoogle Scholar
  27. Marrero JA, Fontana RJ, Barrat A, Askari F, Conjeevaram HS, Su GL, Lok AS (2005) Prognosis of hepatocellular carcinoma: comparison of 7 staging systems in an American cohort. Hepatology 41:707–716PubMedCrossRefGoogle Scholar
  28. Noda T, Sasaki Y, Yamada T, Eguchi H, Yano M, Ohigashi H, Ishikawa O, Imaoka S (2009) Usefulness of the CLIP scoring system for prediction of postoperative prognosis of patients with large hepatocellular carcinoma. J Hepatobiliary Pancreat SurgGoogle Scholar
  29. Okuda K, Ohtsuki T, Obata H, Tomimatsu M, Okazaki N, Hasegawa H, Nakajima Y, Ohnishi K (1985) Natural history of hepatocellular carcinoma and prognosis in relation to treatment. Study of 850 patients. Cancer 56:918–928PubMedCrossRefGoogle Scholar
  30. Parkin DM (1998) The global burden of cancer. Semin Cancer Biol 8:219–235PubMedCrossRefGoogle Scholar
  31. Poon RT, Fan ST (2003) Evaluation of the new AJCC/UICC staging system for hepatocellular carcinoma after hepatic resection in Chinese patients. Surg Oncol Clin N Am 12:35–50 viiiPubMedCrossRefGoogle Scholar
  32. Poon RT, Fan ST, Lo CM, Liu CL, Ng IO, Wong J (2000a) Long-term prognosis after resection of hepatocellular carcinoma associated with hepatitis B-related cirrhosis. J Clin Oncol 18:1094–1101PubMedGoogle Scholar
  33. Poon RT, Fan ST, Ng IO, Wong J (2000b) Significance of resection margin in hepatectomy for hepatocellular carcinoma: a critical reappraisal. Ann Surg 231:544–551PubMedCrossRefGoogle Scholar
  34. Poon D, Anderson BO, Chen LT, Tanaka K, Lau WY, Van Cutsem E, Singh H, Chow WC, Ooi LL, Chow P, Khin MW, Koo WH (2009) Management of hepatocellular carcinoma in Asia: consensus statement from the Asian Oncology Summit 2009. Lancet Oncol 10:1111–1118PubMedCrossRefGoogle Scholar
  35. Ryder S (2005) Predicting survival in early hepatocellular carcinoma. Gut 54:328–329PubMedCrossRefGoogle Scholar
  36. Tarao K, Rino Y, Ohkawa S, Tamai S, Miyakawa K, Takakura H, Endo O, Yoshitsugu M, Watanabe N, Matsuzaki S (2002) Close association between high serum alanine aminotransferase levels and multicentric hepatocarcinogenesis in patients with hepatitis C virus-associated cirrhosis. Cancer 94:1787–1795PubMedCrossRefGoogle Scholar
  37. Ueno S, Tanabe G, Sako K, Hiwaki T, Hokotate H, Fukukura Y, Baba Y, Imamura Y, Aikou T (2001) Discrimination value of the new western prognostic system (CLIP score) for hepatocellular carcinoma in 662 Japanese patients. Cancer of the Liver Italian Program. Hepatology 34:529–534PubMedCrossRefGoogle Scholar
  38. Ueno S, Tanabe G, Nuruki K, Oketani M, Komorizono Y, Hokotate H, Fukukura Y, Baba Y, Imamura Y, Aikou T (2002) Prognosis of hepatocellular carcinoma associated with Child class B and C cirrhosis in relation to treatment: a multivariate analysis of 411 patients at a single center. J Hepatobiliary Pancreat Surg 9:469–477PubMedCrossRefGoogle Scholar
  39. Vauthey JN, Lauwers GY, Esnaola NF, Do KA, Belghiti J, Mirza N, Curley SA, Ellis LM, Regimbeau JM, Rashid A, Cleary KR, Nagorney DM (2002) Simplified staging for hepatocellular carcinoma. J Clin Oncol 20:1527–1536PubMedCrossRefGoogle Scholar
  40. Villa E, Colantoni A, Camma C, Grottola A, Buttafoco P, Gelmini R, Ferretti I, Manenti F (2003) Estrogen receptor classification for hepatocellular carcinoma: comparison with clinical staging systems. J Clin Oncol 21:441–446PubMedCrossRefGoogle Scholar
  41. Wayne JD, Lauwers GY, Ikai I, Doherty DA, Belghiti J, Yamaoka Y, Regimbeau JM, Nagorney DM, Do KA, Ellis LM, Curley SA, Pollock RE, Vauthey JN (2002) Preoperative predictors of survival after resection of small hepatocellular carcinomas. Ann Surg 235:722–730 (discussion 730-1)PubMedCrossRefGoogle Scholar
  42. Wild CP, Hall AJ (2000) Primary prevention of hepatocellular carcinoma in developing countries. Mutat Res 462:381–393PubMedCrossRefGoogle Scholar
  43. Wu M (2001) Clinical advances in primary liver cancer in China. Hepatogastroenterology 48:29–32PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Tian Yang
    • 1
  • Jin Zhang
    • 1
  • Jun-Hua Lu
    • 1
  • Li-Qun Yang
    • 2
  • Guang-Shun Yang
    • 1
  • Meng-Chao Wu
    • 1
  • Wei-Feng Yu
    • 1
    • 2
  1. 1.Department of 2nd Hepatobiliary Surgery, Eastern Hepatobiliary Surgery HospitalSecond Military Medical UniversityYangpu District, ShanghaiChina
  2. 2.Intensive Care Unit, Eastern Hepatobiliary Surgery HospitalSecond Military Medical UniversityShanghaiChina

Personalised recommendations