Surgically Resected Hepatocellular Carcinoma: Protean Yet Predictable

Abstract

In this issue of the Annals of Surgical Oncology, Ramacciato et al. report the results of a study in which they evaluated the new (6th edition) American Joint Committee on Cancer and International Union Against Cancer (AJCC/UICC) staging system for hepatocellular carcinoma (HCC) in a series of 112 patients undergoing resection for HCC. The authors report a homogeneous group of patients (90% had cirrhosis, and 55% had cirrhosis induced by hepatitis C) with small (median tumor size, 4 cm) and solitary HCC (82% of patients). Microscopic vascular invasion was present in only 23 patients (21%). The authors conclude that the 6th edition AJCC/UICC staging system is superior to the preceding one because of its simplicity and more accurate stratification of patients into homogeneous subsets with similar prognosis. In agreement with the evaluation by Poon and Fan, the authors found no improved prognosis for tumors measuring 2 cm or smaller. Furthermore, in multivariate analysis, when the stage was analyzed with other prognostic factors determined in univariate analysis (cirrhosis of viral origin, multiple nodules, and microscopic vascular invasion), stage was the only independent predictor of prognosis. The new staging system for HCC is one of the many staging systems updated in the 6th edition of the AJCC cancer staging manual. In this edition, the staging systems for upper gastrointestinal tract cancers, including HCC, were revised such that stage IV disease is uniformly defined as metastatic disease. The staging system for HCC, which was formerly based on the complex classification of the Liver Cancer Study Group of Japan, was simplified on the basis of a large multicenter multivariate analysis of more than 500 patients undergoing partial hepatectomy for HCC in the United States, Japan, and France. This study included a complete pathologic review of the tumor and underlying liver characteristics that account for the protean presentation of HCC. The T-categories in the new HCC staging system are based on the presence or absence and severity of vascular invasion (T1, solitary tumor without vascular invasion; T2, solitary tumor with vascular invasion or multiple tumors smaller than 5 cm; T3, any tumor with major vascular invasion or multiple tumors larger than 5 cm). Vascular invasion is important because it predicts prognosis after resection or transplantation. A substantial addition to the new system is the provision of a fibrosis factor to reflect the severity of underlying fibrosis (F0, no or moderate fibrosis; F1, severe fibrosis or cirrhosis). Each T-category of the new staging system is affected by the severity of the underlying fibrosis. Thus, the new system recommends that a fibrosis score (F0 or F1), similar to the Edmondson-Steiner nuclear grade (G1 to G4), be added to the tumor stage. What is the relevance of the new AJCC/UICC staging system with regard to other existing staging systems for HCC, such as the Barcelona Cancer Liver Clinic staging system, the Cancer of the Liver Italian Program (CLIP) score, the Okuda staging system, and the Chinese University Prognostic Index? In contrast to those, the AJCC/UICC staging system for HCC is based on a pathologic review of surgical specimens. Received December 9, 2004; accepted January 10, 2005; published online March 14, 2005. Address correspondence and reprint requests to: Jean-Nicolas Vauthey, MD; E-mail: jvauthey@mdanderson.org.