Staging systems for hepatocellular carcinoma: should we all use the BCLC system?

When determining the prognosis of patients with solid tumors, tumor staging and tumor grading are important factors to take into account. Tumor staging describes the extent of an individual’s tumor burden in the original primary organ and spread throughout the body. Staging is important because it helps plan treatment, it can be used to estimate the person’s prognosis (such as the Duke’s classification for colon cancer), and it provides a standardized platform to evaluate new treatment and to compare the results of different studies [1]. In the majority of solid organ tumors, staging is determined at the time of surgery by pathological examination of the resected specimen leading to the Tumor Node Metastasis (TNM) classification. In addition to tumor burden, histological tumor grading systems have been shown to offer prognostic information in some cancers such as prostate, breast and kidney. The importance of tumor grade in planning treatment and in estimating a patient’s prognosis is greater for certain types of cancers, such as the Gleason score in prostate cancer [2]. Tumor burden and grade cannot be assessed in most patients with hepatocellular carcinoma (HCC), because only about a third of the patients will undergo surgical therapies and some of these patients may have received local ablation or intra-arterial chemoembolization prior to surgery limiting the histological examination. The presence of underlying liver cirrhosis in patients with HCC adds an important dimension that cannot be ignored when discussing prognosis and treatment for these patients, and it is what differentiates HCC from other solid tumors. The majority of patients with HCC have underlying cirrhosis, and the degree of hepatic dysfunction determines which treatment can be applied [3]. Another important factor in the prognosis of patients with HCC is performance status, though it is not HCC-specific. Performance status has been shown to be an important prognostic factor in HCC [4]. Therefore, the prognosis of patients with HCC will rely on tumor burden, hepatic function and performance status. Several staging systems have been proposed for HCC that includes the Okuda [5], BCLC (Barcelona Clinic Liver Cancer) [6], CLIP (Cancer of Liver Italian Program) [7], French (Groupe d’Etude de Traitement du Carcinoma Hepatocellulaire) [8], CUPI (Chinese University Prognostic Index) [9], and JIS (Japanese Integrated System) [10] classifications. The CLIP, GRETCH, and CUPI systems were each determined based on the results of a multivariate analysis for survival factors in a cohort of patients with HCC. This leads to several problems limiting their value: applicable only to the population studied (leading to lack of transportability), validation in an independent cohort is critical for the development of such a system and not always performed, not all factors that determine tumor burden, hepatic function or performance status were included, and lack of a link to treatment. Okuda realized that tumor burden and hepatic function were the most important factors that determine prognosis in HCC. However, assessment of tumor burden was crude and applicable only to advanced stages of HCC: tumor occupying more or less than 50% of the liver, and measures of hepatic function included only ascites, albumin, and bilirubin.