LAUSR

Unlike other solid malignancies, the prognosis of hepatocellular carcinoma (HCC) is affected by liver function as well as by the tumor burden, making it difficult to establish an optimal staging system that can be applied in clinical practice. The most commonly used cancer staging system for solid cancers that considers only tumor–node–metastasis, that of the American Joint Committee on Cancer, is only selectively helpful for HCC amenable to resection or transplantation. Historically, the first staging system specific to HCC that incorporated tumorassociated factors and liver function was the OKUDA score developed in 1985. Thereafter, the Cancer of the Liver Italian Program score, introduced in 1998, included serum alpha-fetoprotein (AFP) in addition to the liver function indicated by the Child-Pugh score, portal vein thrombosis, and tumor burden. Unfortunately, the disease extent parameter in both the OKUDA and Cancer of the Liver Italian Program scoring systems was poorly defined, such as hepatic spread of <50% versus 50%. The substantial progress in the management of HCC has decreased the usefulness of these staging systems. The heterogeneity of HCC was partly reflected in a novel staging system proposed in 1999, the Barcelona Clinic Liver Cancer (BCLC) algorithm. Using tumor number, size, Child-Pugh score, and performance status, HCC was classified into five stages, from the very early to the terminal stage. Because of the uniqueness of assigning a treatment modality for a specific stage and the suggestion of an expected overall survival, the BCLC classification has become the most widely used staging system and has been endorsed by international liver societies such as the American Association for the Study of Liver Diseases and the European Association for the Study of the Liver. However, this staging system has several limitations in terms of prognostication, particularly in inoperable patients with BCLC stage B or C, because this system did not consider tumor heterogeneity in these stages. Indeed, linking BCLC-B HCC to a single modality of transarterial chemoembolization and BCLC-C HCC to only sorafenib has been challenged by subsequent studies. Accordingly, the overall adherence to the BCLC algorithm was not so high in real practice. The Hong Kong Liver Cancer staging system, proposed in 2014 and internally validated, tried to address the weaknesses of the BCLC and extend the role of resection and transarterial chemoembolization in subsets of patients with intermediate and advanced stages. However, due to several limitations, this staging system cannot be generalized worldwide. The data were obtained retrospectively from a single institution, which might not allow us to recommend more aggressive treatment in unresectable HCC, such as resection for intermediate-stage HCC or transarterial chemoembolization for advanced HCC. In addition, this system is too complicated to follow. In this regard, the article in this issue of HEPATOLOGY by Borzio et al. presents the ITA.LI.CA Abbreviations: AFP, alpha-fetoprotein; BCLC, Barcelona Clinic Liver Cancer; HCC, hepatocellular carcinoma.