Li et al. BMC Cancer 2010, 10:535 http://www.biomedcentral.com/1471-2407/10/535 R E S E A R C H A R T I C L E Open Access Application of tumor-node-metastasis staging 2002 version in locally advanced hepatocellular carcinoma: is it predictive of surgical outcome? Binkui Li1,2, Yunfei Yuan1,2*, Guihua Chen3, Liru He1,4, Yaqi Zhang1,2, Jinqing Li1,2, Guohui Li1,2, Wan Yee Lau5 Abstract Background: Locally advanced (pT3-4N0M0) hepatocellular carcinoma (HCC) is a heterogeneous group of tumors, which consists of four different categories, including HCC with “multiple tumors more than 5 cm”, “major vascular invasion”, “invasion of adjacent organs”, and “perforation of visceral peritoneum”. The aim of our study was to verify whether the 2002 version of the Tumor-Node-Metastasis staging system could predict surgical outcomes in patients with locally advanced HCC. Methods: We retrospectively reviewed 298 patients with pT3-4N0M0 HCC who underwent hepatic resection from 1993 to 2000 in an academic tertiary hospital. Overall survival (OS) and cumulative recurrence rate (CRR) of the four categories of locally advanced HCC patients were compared. Results: In multivariate analysis, major vascular invasion was identified as the most significant factor (HR = 3.291, 95% CI 2.362-4.584, P < 0.001) followed by cirrhosis status on OS, and was found to be the only independent factor of CRR (HR = 2.242, 95% CI 1.811-3.358, P < 0.001) in patients with locally advanced HCC. Among the four categories of locally advanced HCC, OS was significantly worse, and CRR was significantly higher in patients with HCC with major vascular invasion (pT3) than with multiple tumors more than 5 cm (pT3); or tumor invasion of adjacent organs (pT4); or perforation of visceral peritoneum (pT4). No significant differences were observed in OS or CRR between the latter three groups of patients. Conclusions: HCC with major vascular invasion, which are classified as pT3 under the current TNM staging, have the worst prognosis when compared with the other categories of pT3-4 disease. There is a need to redefine the T classification and to stratify locally advanced HCC. Background Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in the world with a globally increasing annual incidence [1,2]. For accurate prognos- tic assessment after partial hepatectomy and patient selection for adjuvant therapy, the pathologic tumor- node-metastasis (pTNM) staging system has traditionally been used. This TNM staging system has the advantages of a more detailed T classification than in any other sta- ging systems [3]. However, the current 2002 TNM sta- ging system is not completely satisfactory. The * Correspondence: yuanyf@mail.sysu.edu.cn 1State Key Laboratory of Oncology in South China, Guangzhou, China Full list of author information is available at the end of the article stratification and the prognostic classification of advanced T stages of HCC are most debatable [4-7]. In the 2002 version of the TNM staging system, locally advanced HCC consists of four categories of dis- eases, with pT3 being classified as multiple tumors more than 5 cm; or tumors with tumor thrombus within the major branch of portal or hepatic veins, and pT4 being classified as tumors with direct invasion of adjacent organs other than gallbladder; or perforation of visceral peritoneum [8,9]. Although major vascular invasion has been recognized as a very strong predictive factor of dis- mal prognosis, [6,7] and several studies have also shown invasion of adjacent organs or perforation of visceral peritoneum was not definitely associated with a worse survival, [10,11] HCC with invasion of adjacent organs or perforation of visceral peritoneum but not major © 2010 Li et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.