Abstract
It is well known that intermediate stage hepatocellular carcinoma (HCC) encompasses the widest class of patients with this disease. The main characteristic of this special sub-group of patients is that it is extensively heterogenous. This substantial heterogeneity is due to the wide range of liver functions of such patients and variable tumor numbers and sizes. Real world clinical data show huge support for transarterial chemo-embolization (TACE) as a therapeutic modality for intermediate stage HCC, applied in 50%-60% of those class of patients. There are special considerations in various international guidelines regarding treatment allocation in intermediate stage HCC. There is an epidemiological difference in HCC in eastern and western cohorts, and various guidelines have been proposed. In patients with HCC, it has frequently been reported that there is poor correlation between the clinical benefit and real gain in patient condition and the conventional way of tumor response assessment after locoregional treatments. This is due to the evaluation criteria in addition to the scoring systems used for treatment allocation in those patients. It became clear that intermediate stage HCC patients receiving TACE need a proper prognostic score that offers valid clinical prediction and supports proper decision-making. Also, it is the proper time to study more treatment options beyond TACE, such as multimodal regimens for this class of patients. In this review, we tried to provide a summary of the challenges and future directions in managing patients with intermediate stage HCC.