Prognostic Value and Clinical Relevance of the 6th Edition 2002 American Joint Committee on Cancer Staging System in Patients with Resectable Hepatocellular Carcinoma

National Yang Ming University, T’ai-pei, Taipei, Taiwan
Journal of the American College of Surgeons (Impact Factor: 5.12). 11/2006; 203(4):426-35. DOI: 10.1016/j.jamcollsurg.2006.06.030
Source: PubMed


A simplified American Joint Committee on Cancer (AJCC) TNM staging system for hepatocellular carcinoma (HCC) (the 6th edition) was proposed in 2002. In this study, we validated the prognostic value of the staging system in a patient cohort undergoing hepatic resection with longterm followup.
From a prospective database, the study cohort consisted of 440 patients who underwent curative hepatic resection for HCC between July 1991 and January 1999. Median followup time was 66 months. Multivariate analysis was performed to identify the independent prognostic factors related to postoperative survival. Patients were staged according to both the 5th edition (TNM-5) and 6th edition (TNM-6) AJCC TNM staging criteria.
The independent prognostic factors included major vascular invasion, microvascular invasion, surgical margin < 1 cm, indocyanine green retention rate at 15 minutes > 10%, multiple tumors, tumor rupture, male, and serum aspartate aminotransferase > 90 U/L. The breakdown by TNM-5 staging: I, 27 (6.1%); II, 108 (24.5%); III, 218 (49.5%); and IVA, 87 (19.8%) and by TNM-6 staging: I, 120 (27.3%); II, 170 (38.6%); and III, 150 (34.1%). When stratified according to the TNM-5 system, difference in survival was notable between stages II and IIIA (p < 0.001), between stages IIIA and IVA (p < 0.001), but not between stages I and II (p > 0.05). When stratified according to the TNM-6 system, difference in survival was considerable between stages I and II (p < 0.01), stages II and III (p < 0.001), and stages I and III (p < 0.001).
Overall, the TNM-6 staging system appears to provide a reliable prognostic classification of HCC patients and is simpler to use than the TNM-5 staging system.

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    • "Several staging systems for HCC have been proposed as the Okuda [7], TNM [8], the Cancer of the Liver Italian Program (CLIP) [9], the Groupe d’Etude et de Traitement du Carcinome Hepatocellulaire Prognostic classification (GETCH) [10], Barcelona Clinic Liver Cancer (BCLC) [11], Vienna classification [12], Chinese University Prognostic Index (CUPI) [13], Japan Integrated Staging (JIS) score [14] and Tokyo [15] staging system. "
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    ABSTRACT: Several hepatocellular carcinoma (HCC) staging systems are available. Although the European Association for Study of Liver Diseases (EASL) and American Association for the Study of Liver Diseases (AASLD) recommended the use of Barcelona Clinic Liver Cancer (BCLC), many studies in different populations revealed heterogeneous results. The aim of this study was to compare different staging systems for predicting prognosis and survival, and for stratifying HCC patients for treatment at a national referral centre for liver disease in Egypt. 2000 Patients were included in this study. Baseline demographic, clinical, laboratory, and radiological data were determined at diagnosis. Patients were stratified using the Okuda, BCLC, Cancer of the Liver Italian Program (CLIP), and Japan Integrated Staging (JIS). Patients' survival in different stages within each staging system and the validity of the system in predicting survival were compared. The overall survival was 15 months. The 1-, 2-, 3- and 4-year survival of the entire cohort was 56%, 34%, 25% and 15% respectively. The presence of ascites, multiple focal lesions, large tumour size >5 cm, portal vein thrombosis, extra-hepatic spread, AFP≥200 ng/ml and poor Child score were independent predictors of survival (p<0.001). All staging systems were significant in determining overall survival in univariate and multivariate analyses. BCLC was the most predictive staging system for the whole cohort (p<0.001). Among the subgroup of patients offered potentially curative therapy, BCLC was the most informative system in predicting patient survival (p<0.001). For patients with advanced HCC not amenable for specific therapy, CLIP was the best staging system for predicting prognosis (p<0.001). BCLC staging system provided the best prognostic stratification for HCC patients. However, CLIP score has the highest stratification ability in patients with advanced HCC highlighting the importance of including AFP in best staging system.
    PLoS ONE 03/2014; 9(3):e90929. DOI:10.1371/journal.pone.0090929 · 3.23 Impact Factor
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    • "All of this evidence, including our results, support TNM-7 is superior to TNM- 6. However, studies (Chun et al. 2011; Poon et al. 2003; Lei et al. 2006; Kee et al. 2007; Minagawa et al. 2007; Li et al. 2010; Cheng et al. 2011) reported that the prognostic power of TNM-7 was relatively low in advanced stages. Chun et al. (2011) demonstrated that although a significant difference between adjoining early stages was identified, there was no significant difference in survival between adjoining advanced stages of TNM-7 (Cstage IIIB; all P [ 0.05). "
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    ABSTRACT: To evaluate the accuracy of the 7th edition of the American Joint Committee on Cancer staging system (TNM-7) for patients undergoing hepatectomy for hepatocellular carcinoma (HCC) and to propose a modified TNM system for better prediction of survival. Clinico-pathological data for 1,313 patients who underwent hepatectomy as initial treatment for HCC between 2000 and 2008 were retrieved from a prospective database. Overall survival (OS) and disease-free survival (DFS) were analyzed to evaluate the predictive value. The 1-, 3-, 5-year OS and DFS of 1,313 patients were 79.2, 55.4, 45.5 %, and 52.6, 36.1, 31.8 %, respectively. Multivariate analysis revealed that major vascular invasion was the most important prognostic factor for both OS and DFS, along with tumour number and size. Patients with pT1 and pT2 disease had significantly better OS and DFS than those with pT3 disease (P < 0.001). There was no significant difference between pT3a and pT4 (P = 0.552) but patients with pT3b disease had a worse OS and DFS than those with pT4 disease (P = 0.006 and P < 0.001, respectively). A modified TNM system within the existing framework was proposed to combine the current pT3a and pT4 together as the new pT3 and to change pT3b to the new pT4. Analysis showed that this modified system had a better prognostic power than either TNM-6 or TNM-7. TNM-7 would seem to be inaccurate for staging advanced HCC. The modified system can improve both the prognostic accuracy and the hazard discrimination of disease to be consistent among subgroups of HCC.
    Journal of Cancer Research and Clinical Oncology 08/2013; 139(10). DOI:10.1007/s00432-013-1497-y · 3.08 Impact Factor
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    • "This is why the Child-Pugh score, although not being an HCC staging system in its actual sense, has been used to stratify HCC patients as well. Nevertheless, traditional uni-dimensional classifications like the TNM-system [5] or the Child-Pugh-score [6], exclusively taking into account tumor stage or liver dysfunction, respectively, do not account for the complexity of HCC in cirrhosis. As a consequence, multidimensional staging systems which include both the extension of tumor and liver function parameters (sometimes plus general health variables) have been developed: Okuda [7], Barcelona Clinic Liver Cancer (BCLC) [8], Cancer of the Liver Italian Program (CLIP) [9], Groupe d'Etude et de Traitement du Carcinome Hépatocellulaire (GETCH) [10] and Japan Integrated Staging (JIS) [11] [For details, see supporting information tables S1, S2, S3, S4, S5, S6, S7, S8]. "
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    ABSTRACT: HCC is diagnosed in approximately half a million people per year, worldwide. Staging is a more complex issue than in most other cancer entities and, mainly due to unique geographic characteristics of the disease, no universally accepted staging system exists to date. Focusing on survival rates we analyzed demographic, etiological, clinical, laboratory and tumor characteristics of HCC-patients in our institution and applied the common staging systems. Furthermore we aimed at identifying the most suitable of the current staging systems for predicting survival. Overall, 405 patients with HCC were identified from an electronic medical record database. The following seven staging systems were applied and ranked according to their ability to predict survival by using the Akaike information criterion (AIC) and the concordance-index (c-index): BCLC, CLIP, GETCH, JIS, Okuda, TNM and Child-Pugh. Separately, every single variable of each staging system was tested for prognostic meaning in uni- and multivariate analysis. Alcoholic cirrhosis (44.4%) was the leading etiological factor followed by viral hepatitis C (18.8%). Median survival was 18.1 months (95%-CI: 15.2-22.2). Ascites, bilirubin, alkaline phosphatase, AFP, number of tumor nodes and the BCLC tumor extension remained independent prognostic factors in multivariate analysis. Overall, all of the tested staging systems showed a reasonable discriminatory ability. CLIP (closely followed by JIS) was the top-ranked score in terms of prognostic capability with the best values of the AIC and c-index (AIC 2286, c-index 0.71), surpassing other established staging systems like BCLC (AIC 2343, c-index 0.66). The unidimensional scores TNM (AIC 2342, c-index 0.64) and Child-Pugh (AIC 2369, c-index 0.63) performed in an inferior fashion. Compared with six other staging systems, the CLIP-score was identified as the most suitable staging system for predicting prognosis in a large German cohort of predominantly non-surgical HCC-patients.
    PLoS ONE 10/2012; 7(10):e45066. DOI:10.1371/journal.pone.0045066 · 3.23 Impact Factor
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