Downstaging Conversion Therapy in Patients With Initially Unresectable Advanced Hepatocellular Carcinoma: An Overview

Abstract

The high mortality rate associated with hepatocellular carcinoma (HCC) is partly due to the high proportion of patients who present with advanced stage disease at diagnosis, for whom there are limited treatment options. For selected patients with initially unresectable HCC, locoregional and/or systemic treatments can result in tumor downstaging and consequently provide opportunities for surgical intervention and the potential for long-term survival. Therefore, the key aim of ‘conversion therapy’ is to reduce tumor burden so that patients become amenable to surgical resection. Various therapies have been investigated as candidates for downstaging patients with potentially resectable HCC including transarterial chemoembolization, transarterial radioembolization with yttrium-90 microspheres, radiotherapy, systemic therapies and combination or multimodality treatment approaches. However, downstaging conversion therapy remains controversial and there are several challenges such as defining the criteria used to identify the population of patients who are ‘potentially resectable’, the criteria used to define successful downstaging, and the optimum treatment approach to maximize the success of downstaging therapy. In this review article, we summarize clinical experience and evidence of downstaging conversion treatment in patients identified as having ‘potentially resectable’ HCC.

Lenvatinib plus anti-PD-1 therapy represents a feasible conversion resection strategy for patients with initially unresectable hepatocellular carcinoma: A retrospective study

“…Systemic therapies for HCC mainly include tyrosine kinase inhibitors (TKIs), immunotherapy and chemotherapy. Traditional sorafenib treatment had a relatively low tumor response rate and thus was not considered as part of conversion therapy for advanced HCC (8)(9)(10). Lenvatinib has been approved as a new first-line option for advanced HCCs and is associated with significantly higher overall response rates than sorafenib in unresectable HCC (11,12).…”

Conversion therapy with an immune checkpoint inhibitor and an antiangiogenic drug for advanced hepatocellular carcinoma: A review

“…Therefore, the current authors propose to focus on the survival benefits for patients and to explore conversion therapy with a combination of an ICI and an AAD for advanced HCC. Conversion therapy for advanced HCC mainly includes the following two connotations: a) conversion to surgical resectability and b) the possibility of an oncological benefit (16,30,31).…”

Efficacy of transarterial chemoembolization monotherapy or combination conversion therapy in unresectable hepatocellular carcinoma: A systematic review and meta-analysis

“…In recent years, conversion therapy for unresectable hepatocellular carcinoma (uHCC) has attracted increased interest. Conversion therapy is designed to achieve tumor downstaging and provide patients with initially unresectable or borderline resectable malignancies the opportunity to undergo radical resection ( 3 ). This approach is now the established treatment strategy for many solid tumors, including colorectal cancer ( 4 ).…”

“…Common systemic treatments include chemotherapy, targeted therapy, and immunotherapy ( 8 ). With the popularity of other treatments, such as local or systemic treatments, combination therapy seems to be the trend, which may provide cumulative benefits in efficacy beyond what either approach alone provides ( 3 ). Effective conversion therapy strategies are still being explored.…”