Yonsei Med J.  2019 Feb;60(2):140-147. 10.3349/ymj.2019.60.2.140.

The 7th/8th American Joint Committee on Cancer and the Modified Union for International Cancer Control Staging System for Hepatocellular Carcinoma

• Kim IG
• Hu XG
• Wang HJ
• Kim BW
• Hong SY
• Shen XY

• KMID: 2431630
• DOI: http://doi.org/10.3349/ymj.2019.60.2.140

Abstract

PURPOSE
Although many staging systems have been proposed for hepatocellular carcinoma (HCC), there is no globally accepted system due to the extreme heterogeneity of the disease. We aimed to compare the results of the 7th/8th American Joint Committee on Cancer (AJCC) and the modified Union for International Cancer Control (mUICC) staging systems in patients with HCC.
MATERIALS AND METHODS
We collected data from 792 patients who underwent hepatic resection at our center. The Kaplan-Meier method was used to determine disease-free survival and overall survival. To evaluate homogeneity, "˜-2 log likelihood' was calculated using Cox proportional hazards regression. To measure discriminatory ability, the linear trend chi method and the Cochran-Armitage test for trend were used. The ability to accurately predict survival was verified by cross-validation analysis.
RESULTS
Kaplan-Meier curves for disease-free survival and overall survival showed mUICC to be superior to the 7th/8th AJCC. The homogeneity test indicated that mUICC was the best for both disease-free survival and overall survival. In the discriminatory ability test, the chi-square value of mUICC was the best for disease-free survival, while the 7th AJCC had the best value for overall survival. In the cross-validation analysis, all three staging systems had significant predictive power.
CONCLUSION
mUICC seemed to be superior to the 7th/8th AJCC after analyzing the data of our surgical patients, although the geographic heterogeneity of HCC might result in differences between the staging systems. We believe that, while the three staging systems allow for the clear stratification of patients into prognostic groups, mUICC may be more appropriate in HCC.

Keyword

Hepatocellular carcinoma; staging; survival analysis

MeSH Terms

Carcinoma, Hepatocellular*
Disease-Free Survival
Humans
Joints*
Methods
Population Characteristics
Survival Analysis

Figure

• 

  Fig. 1 Disease-free survival and overall survival in 7th American Joint Committee on Cancer (AJCC). (A) Kaplan-Meier curve shows disease-free survival of patients with 95% confidence interval according to 7th AJCC staging system. p values were from log-rank test. (B) Kaplan-Meier curve shows overall survival of patients with 95% confidence interval according to 7th AJCC staging system. p values were from log-rank test.

• 

  Fig. 2 Disease-free survival and overall survival in 8th American Joint Committee on Cancer (AJCC). (A) Kaplan-Meier curve shows disease-free survival of patients with 95% confidence interval according to 8th AJCC staging system. p values were from log-rank test. (B) Kaplan-Meier curve shows overall survival of patients with 95% confidence interval according to 8th AJCC staging system. p values were from log-rank test.

• 

  Fig. 3 Disease-free survival and overall survival in modified Union for International Cancer Control (mUICC). (A) Kaplan-Meier curve shows disease-free survival of patients with 95% confidence interval according to mUICC staging system. p values were from log-rank test. (B) Kaplan-Meier curve shows overall survival of patients with 95% confidence interval according to mUICC staging system. p values were from log-rank test.

Reference

1. Henderson JM, Sherman M, Tavill A, Abecassis M, Chejfec G, Gramlich T. AHPBA/AJCC consensus conference on staging of hepatocellular carcinoma: consensus statement. HPB (Oxford). 2003; 5:243–250. PMID: 18332995.

2. Subramaniam S, Kelley RK, Venook AP. A review of hepatocellular carcinoma (HCC) staging systems. Chin Clin Oncol. 2013; 2:33. PMID: 25841912.

3. Kinoshita A, Onoda H, Fushiya N, Koike K, Nishino H, Tajiri H. Staging systems for hepatocellular carcinoma: current status and future perspectives. World J Hepatol. 2015; 7:406–424. PMID: 25848467.

4. Yu SJ. A concise review of updated guidelines regarding the management of hepatocellular carcinoma around the world: 2010-2016. Clin Mol Hepatol. 2016; 22:7–17. PMID: 27044761.

5. Jang JY, Lee JS, Kim HJ, Shim JJ, Kim JH, Kim BH, et al. The general rules for the study of primary liver cancer. J Liver Cancer. 2017; 17:19–44.

6. Kim T, Kim BW, Wang HJ, Lee HY, Won JH, Kim J, et al. Quantitative assessment of the portal pressure for the liver surgery using serological tests. Ann Surg. 2016; 264:330–338. PMID: 26587849.

7. Chun YH, Kim SU, Park JY, Kim DY, Han KH, Chon CY, et al. Prognostic value of the 7th edition of the AJCC staging system as a clinical staging system in patients with hepatocellular carcinoma. Eur J Cancer. 2011; 47:2568–2575. PMID: 21835608.

8. Minagawa M, Ikai I, Matsuyama Y, Yamaoka Y, Makuuchi M. Staging of hepatocellular carcinoma: assessment of the Japanese TNM and AJCC/UICC TNM systems in a cohort of 13,772 patients in Japan. Ann Surg. 2007; 245:909–922. PMID: 17522517.

9. Liang KY, Zeger SL. Longitudinal data analysis using generalized linear models. Biometrika. 1986; 73:13–22.

10. Yamanaka N, Okamoto E, Kuwata K, Tanaka N. A multiple regression equation for prediction of posthepatectomy liver failure. Ann Surg. 1984; 200:658–663. PMID: 6486915.

11. Makuuchi M, Kosuge T, Takayama T, Yamazaki S, Kakazu T, Miyagawa S, et al. Surgery for small liver cancers. Semin Surg Oncol. 1993; 9:298–304. PMID: 8210909.

12. Guglielmi A, Ruzzenente A, Conci S, Valdegamberi A, Iacono C. How much remnant is enough in liver resection? Dig Surg. 2012; 29:6–17. PMID: 22441614.

13. Shimada M, Takenaka K, Kawahara N, Kajiyama K, Yamamoto K, Shirabe K, et al. Surgical treatment strategy for patients with stage IV hepatocellular carcinoma. Surgery. 1996; 119:517–522. PMID: 8619206.

14. Yamamoto K, Takenaka K, Kawahara N, Shimada M, Shirabe K, Itasaka H, et al. Indications for palliative reduction surgery in advanced hepatocellular carcinoma. The use of a remnant tumor index. Arch Surg. 1997; 132:120–123. PMID: 9041912.

15. Chirica M, Scatton O, Massault PP, Aloia T, Randone B, Dousset B, et al. Treatment of stage IVA hepatocellular carcinoma: should we reappraise the role of surgery? Arch Surg. 2008; 143:538–543. PMID: 18559745.

16. Kim BW, Park YK, Kim YB, Wang HJ, Kim MW. Salvage liver transplantation for recurrent hepatocellular carcinoma after liver resection: feasibility of the Milan criteria and operative risk. Transplant Proc. 2008; 40:3558–3561. PMID: 19100437.

17. Graf D, Vallböhmer D, Knoefel WT, Kröpil P, Antoch G, Sagir A, et al. Multimodal treatment of hepatocellular carcinoma. Eur J Intern Med. 2014; 25:430–437. PMID: 24666568.

18. Maida M, Orlando E, Cammà C, Cabibbo G. Staging systems of hepatocellular carcinoma: a review of literature. World J Gastroenterol. 2014; 20:4141–4150. PMID: 24764652.

19. Fong ZV, Tanabe KK. The clinical management of hepatocellular carcinoma in the United States, Europe, and Asia: a comprehensive and evidence-based comparison and review. Cancer. 2014; 120:2824–2838. PMID: 24897995.

20. Kee KM, Wang JH, Lin CY, Wang CC, Cheng YF, Lu SN. Validation of the 7th edition TNM staging system for hepatocellular carcinoma: an analysis of 8,828 patients in a single medical center. Dig Dis Sci. 2013; 58:2721–2728. PMID: 23703450.

21. Lei HJ, Chau GY, Lui WY, Tsay SH, King KL, Loong CC, et al. 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. 2006; 203:426–435. PMID: 17000385.

22. Vauthey JN, Lauwers GY, Esnaola NF, Do KA, Belghiti J, Mirza N, et al. Simplified staging for hepatocellular carcinoma. J Clin Oncol. 2002; 20:1527–1536. PMID: 11896101.

23. Huang J, Zhang Y, Peng Z, Gao H, Xu L, Jiao LR, et al. A modified TNM-7 staging system to better predict the survival in patients with hepatocellular carcinoma after hepatectomy. J Cancer Res Clin Oncol. 2013; 139:1709–1719. PMID: 23982274.

24. Chan AC, Fan ST, Poon RT, Cheung TT, Chok KS, Chan SC, et al. Evaluation of the seventh edition of the American Joint Committee on Cancer tumour-node-metastasis (TNM) staging system for patients undergoing curative resection of hepatocellular carcinoma: implications for the development of a refined staging system. HPB (Oxford). 2013; 15:439–448. PMID: 23659567.

25. Kudo M, Chung H, 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 Gastroenterol. 2003; 38:207–215. PMID: 12673442.

26. Kudo M, Chung H, Haji S, Osaki Y, Oka H, Seki T, et al. Validation of a new prognostic staging system for hepatocellular carcinoma: the JIS score compared with the CLIP score. Hepatology. 2004; 40:1396–1405. PMID: 15565571.

27. Ikai I, Takayasu K, Omata M, Okita K, Nakanuma Y, Matsuyama Y, et al. A modified Japan Integrated Stage score for prognostic assessment in patients with hepatocellular carcinoma. J Gastroenterol. 2006; 41:884–892. PMID: 17048053.

28. Kitai S, Kudo M, Minami Y, Ueshima K, Chung H, Hagiwara S, et al. A new prognostic staging system for hepatocellular carcinoma: value of the biomarker combined Japan integrated staging score. Intervirology. 2008; 51(Suppl 1):86–94. PMID: 18544953.

29. Yen YH, Changchien CS, Wang JH, Kee KM, Hung CH, Hu TH, 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. Dig Liver Dis. 2009; 41:431–441. PMID: 19185555.

30. Meinecke AK, Welsing P, Kafatos G, Burke D, Trelle S, Kubin M, et al. Series: pragmatic trials and real world evidence: Paper 8. Data collection and management. J Clin Epidemiol. 2017; 91:13–22. PMID: 28716504.