Treatment of Hepatocellular Carcinoma in the Precision Medicine Era: From Treatment Stage Migration to Therapeutic Hierarchy

Abstract

Treatment allocation is extremely complex in patients with hepatocellular carcinoma (HCC) because this neoplasm arises, in most cases, in patients with cirrhosis and additional comorbidities. The “stage hierarchy” approach, which involves linking each stage (or substage) of the disease to a specific treatment, has become the main proposed treatment strategy for the clinical management of HCC, particularly in the West. The Barcelona Clinic Liver Cancer (BCLC) scheme serves as the main example of the application of this strategy. In an attempt to increase the plasticity of the “stage hierarchy” approach as well as its adaptability to the requirements of real‐world clinical practice, the latest versions of European and American guidelines have introduced certain relevant elements of flexibility, which were not intrinsic to the original BCLC scheme. These elements are as follows: the “treatment stage migration” strategy, which allows moving to another treatment (generally the one that is associated with the subsequent stage) if the approach linked with the current stage proves to be unfeasible, and the “treatment stage alternative” approach, which proposes further therapeutic options for each BCLC‐defined stage. In regard to most of the solid cancers, another potential strategy is to consider the treatment decision to be hierarchically dictated by the efficacy of each therapy with complete or partial independence from the tumor stage. This concept of “therapeutic hierarchy” has been historically endorsed by the Asia‐Pacific treatment algorithm as well as by the recent Italian multisociety guidelines. The present review provides a critical analysis of the different conceptual approaches to HCC management, highlighting their advantages and disadvantages and focusing on the remarkable differences between the stage‐guided and the hierarchical strategies.

Comparing the efficacy and safety of second-line therapies for advanced hepatocellular carcinoma: a network meta-analysis of phase III trials

“…cabozantinib, regorafenib, lenvatinib, ramucirumab and sorafenib) and three kinds of immunotherapy (nivolumab, pembrolizumab and nivolumab plus ipilimumab) have been recommended by NCCN guidelines (version 2020) based on findings from several recent clinical trials. 14 The current challenge is to better A. Each cell of the block contains the pooled HR and 95% credibility intervals for OS and PFS; significant results are in bold.…”

KRT23 Acts as an Oncogene in Hepatocellular Carcinoma by Regulating P21 via PI3K/AKT/GSK3β Pathway

“…Once discovered, a great deal of HCC patients have missed the best opportunity for surgical resection, following that 70% patients undertake recurrence within 5 years . Furthermore, HCC is an aggressive solid tumor easily non-sensitive to chemotherapeutics applied at present 13 . Above all, it's imperative to improve the e cacy for identi cation of novel biomarkers at preliminary stage of HCC and then make therapies for HCC much more costeffective.Located on chromosome 17q21.2 and with a molecular weight of 48 kDa, KRT23 expresses a 1.65 kb mRNA and has been reported to have some function in several cancers.Protein KRT23 was highly upregulated in primary rectal cancer, which was analyzed by immunochemistry 14 .…”

Hepatocellular Carcinoma: A Review

“…Various studies have also shown superior results for aggressive surgical approach than locoregional therapy in HCC. Therefore, the concept of "treatment stage migration" is emerging with either "left to right" or even "right to left" shift for selection of therapy in the BCLC algorithm (28). This means considering liver resection in patients with either vascular invasion or consideration of liver transplantation in patients with downstaging of tumor with locoregional therapy or outside Milan's criteria (29)(30)(31).…”