Many staging systems of hepatocellular carcinoma (HCC) were established; however, there is no consensus on which is proper in predicting prognosis. This study aims to evaluate various commonly used staging systems of HCC. Patients who underwent surgery during 2001–2007 were included. All patient data were retrospectively staged using six staging systems, that are American Joint Committee on Cancer (AJCC) Tumour-Node-Metastasis (TNM), Okuda staging, Cancer of the Liver Italian Program (CLIP), Barcelona Clinic Liver Cancer (BCLC), Chinese University Prognostic Index (CUPI), and Japan Integrated Staging (JIS). Child-Pugh classification was also evaluated. The staging systems were compared by mean of overall and disease-free survival. Total of 99 patient data were enrolled in the analyses. All staging systems except Okuda were significant in determining overall survival in univariate analyses. In multivariate analyses, TNM and Child-Pugh demonstrated better predictive power for overall survival. In terms of disease-free survival, univariate analyses revealed that TNM, CLIP, BCLC, CUPI, and JIS were significant, and TNM was the best predictive staging system in multivariate analyses. In our study, TNM and Child-Pugh are the representative systems in predicting survival of HCC patients who undergo surgical resection. Moreover, they are practical and easily assessable in clinical practice. 1. Background Hepatocellular carcinoma (HCC) is the most common primary malignancy of liver and one of the most common malignancies especially in Eastern and Southeastern Asia. The most important risk factors of HCC are chronic hepatitis B, C and cirrhosis. In malignancy diseases, staging system is important because it defines prognosis and is a guiding tool for treatment options and also a research tool for comparison between different groups and trials . American Joint Committee on Cancer (AJCC) uses tumour-node-metastasis (TNM) system as staging system for many malignancy diseases to predict prognosis . Nevertheless, in HCC, AJCC/TNM system fails to stratify patients adequately with respect to prognosis because TNM system evaluates only tumour extension. Since the remnant liver function is another important factor to prognosis of patients with HCC beside tumour burden; therefore, the staging system for HCC should include these both factors . Staging systems that include liver function status were first proposed by Okuda et al. in 1985 based on study of 850 HCC patients . This Okuda staging system was consisted of tumour load, ascites, albumin, and bilirubin.
S. Wildi, B. C. Pestalozzi, L. McCormack, and P. A. Clavien, “Critical evaluation of the different staging systems for hepatocellular carcinoma,” The British Journal of Surgery, vol. 91, no. 4, pp. 400–408, 2004.
E. S. Bialecki and A. M. Di Bisceglie, “Clinical presentation and natural course of hepatocellular carcinoma,” The European Journal of Gastroenterology and Hepatology, vol. 17, no. 5, pp. 485–489, 2005.
The Cancer of the Liver Italian Program (CLIP) investigators, “A new prognostic system for hepatocellular carcinoma: a retrospective study of 435 patients,” Hepatology, vol. 28, no. 3, pp. 751–755, 1998.
The Cancer of the Liver Italian Program (CLIP) investigators, “Prospective validation of the CLIP score: a new prognostic system for patients with cirrhosis and hepatocellular carcinoma,” Hepatology, vol. 31, no. 4, pp. 840–845, 2000.
T. W. Leung, A. M. Tang, B. Zee et al., “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, vol. 94, no. 6, pp. 1760–1769, 2002.
M. Kudo, H. Chung, and Y. Osaki, “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),” Journal of Gastroenterology, vol. 38, no. 3, pp. 207–215, 2003.
M. M. Oken, R. H. Creech, D. C. Tormey, et al., “Toxicology and response criteria of the Eastern Cooperative Oncology Group,” The American Journal of Clinical Oncology, vol. 5, no. 6, pp. 649–655, 1982.
Y. H. Yen, C. S. Changchien, J. H. Wang et al., “A modified TNM-based Japan Integrated Score combined with AFP level may serve as a better staging system for early-stage predominant hepatocellular carcinoma patients,” Digestive and Liver Disease, vol. 41, no. 6, pp. 431–441, 2009.
T. Yau, J. Y. Yao, P. Chan, K. Ng, S. T. Fan, and R. T. Poon, “A new prognostic score system in patients with advanced hepatocellular carcinoma not amendable to locoregional therapy,” Cancer, vol. 113, no. 10, pp. 2742–2751, 2008.
C. H. Chen, F. C. Hu, G. T. Huang et al., “Applicability of staging systems for patients with hepatocellular carcinoma is dependent on treatment method—analysis of 2010 Taiwanese patients,” The European Journal of Cancer, vol. 45, no. 9, pp. 1630–1639, 2009.
W. Lu, J. Dong, Z. Huang, D. Guo, Y. Liu, and S. Shi, “Comparison of four current staging systems for Chinese patients with hepatocellular carcinoma undergoing curative resection: Okuda, CLIP, TNM and CUPI,” Journal of Gastroenterology and Hepatology, vol. 23, no. 12, pp. 1874–1878, 2008.
F. Farinati, A. Sergio, A. Baldan et al., “Early and very early hepatocellular carcinoma: when and how much do staging and choice of treatment really matter? A multi-center study,” BMC Cancer, vol. 9, p. 33, 2009.
L. Zhou, J. A. Rui, S. B. Wang, S. G. Chen, and Q. Qu, “LCSGJ-T classification, 6th or 5th edition TNM staging did not independently predict the long-term prognosis of HBV-related hepatocellular carcinoma after radical hepatectomy,” Journal of Surgical Research, vol. 159, no. 1, pp. 538–544, 2010.
J. M. Henderson, M. Sherman, A. Tavill, M. Abecassis, G. Chejfec, and T. Gramlich, “AHPBA/AJCC consensus conference on staging of hepatocellular carcinoma: consensus statement,” Journal of the International Hepato Pancreato Biliary Association, vol. 5, no. 4, pp. 243–250, 2003.
Y. H. Huang, C. H. Chen, T. T. Chang et al., “Evaluation of predictive value of CLIP, Okuda, TNM and JIS staging systems for hepatocellular carcinoma patients undergoing surgery,” Journal of Gastroenterology and Hepatology, vol. 20, no. 5, pp. 765–771, 2005.
T. W. Chen, C. M. Chu, J. C. Yu et al., “Comparison of clinical staging systems in predicting survival of hepatocellular carcinoma patients receiving major or minor hepatectomy,” The European Journal of Surgical Oncology, vol. 33, no. 4, pp. 480–487, 2007.
A. Nanashima, K. Omagari, S. Tobinaga et al., “Comparative study of survival of patients with hepatocellular carcinoma predicted by different staging systems using multivariate analysis,” The European Journal of Surgical Oncology, vol. 31, no. 8, pp. 882–890, 2005.
K. Kondo, K. Chijiiwa, M. Nagano et al., “Comparison of seven prognostic staging systems in patients who undergo hepatectomy for hepatocellular carcinoma,” Hepato-Gastroenterology, vol. 54, no. 77, pp. 1534–1538, 2007.
J. Seong, S. J. Shim, I. J. Lee, K. H. Han, C. Y. Chon, and S. H. Ahn, “Evaluation of the prognostic value of Okuda, Cancer of the Liver Italian Program, and Japan Integrated Staging systems for hepatocellular carcinoma patients undergoing radiotherapy,” International Journal of Radiation Oncology Biology Physics, vol. 67, no. 4, pp. 1037–1042, 2007.
J. K. Cho, J. W. Chung, J. K. Kim, et al., “Comparison of 7 staging systems for patients with hepatocellular carcinoma undergoing transarterial chemoembolization,” Cancer, vol. 23, pp. 1874–1878, 2008.
H. Toyoda, T. Kumada, S. Kiriyama et al., “Comparison of the usefulness of three staging systems for hepatocellular carcinoma (CLIP, BCLC, and JIS) in Japan,” The American Journal of Gastroenterology, vol. 100, no. 8, pp. 1764–1771, 2005.
H. Chung, M. Kudo, S. Takahashi et al., “Comparison of three current staging systems for hepatocellular carcinoma: Japan integrated staging score, new Barcelona Clinic Liver Cancer staging classification, and Tokyo score,” Journal of Gastroenterology and Hepatology, vol. 23, no. 3, pp. 445–452, 2008.
U. Cillo, M. Bassanello, A. Vitale et al., “The critical issue of hepatocellular carcinoma prognostic classification: which is the best tool available?” Journal of Hepatology, vol. 40, no. 1, pp. 124–131, 2004.
A. Guglielmi, A. Ruzzenente, S. Pachera et al., “Comparison of seven staging systems in cirrhotic patients with hepatocellular carcinoma in a cohort of patients who underwent radiofrequency ablation with complete response,” The American Journal of Gastroenterology, vol. 103, no. 3, pp. 597–604, 2008.
S. Collette, F. Bonnetain, X. Paoletti et al., “Prognosis of advanced hepatocellular carcinoma: comparison of three staging systems in two French clinical trials,” Annals of Oncology, vol. 19, no. 6, pp. 1117–1126, 2008.
C. Cammà, V. Di Marco, G. Cabibbo et al., “Survival of patients with hepatocellular carcinoma in cirrhosis: a comparison of BCLC, CLIP and GRETCH staging systems,” Alimentary Pharmacology and Therapeutics, vol. 28, no. 1, pp. 62–75, 2008.
J. N. Vauthey, D. Ribero, E. K. Abdalla et al., “Outcomes of liver transplantation in 490 patients with hepatocellular carcinoma: validation of a uniform staging after surgical treatment,” Journal of the American College of Surgeons, vol. 204, no. 5, pp. 1016–1028, 2007.
H. Nathan, G. Mentha, H. P. Marques et al., “Comparative performances of staging systems for early hepatocellular carcinoma,” Journal of the International Hepato Pancreato Biliary Association, vol. 11, no. 5, pp. 382–390, 2009.