Abstract

Liver cancer, specifically hepatocellular carcinoma (HCC), is the sixth most common cancer and the third leading cause of cancer
mortality worldwide. The development of effective systemic therapies, particularly those involving immune-checkpoint inhibitors (ICIs), has
substantially improved the outcomes of patients with advanced-stage HCC. Approximately 30% of patients are diagnosed with early stage
disease and currently receive potentially curative therapies, such as resection, liver transplantation or local ablation, which result in
median overall survival durations beyond 60 months. Nonetheless, up to 70% of these patients will have disease recurrence within 5 years
of resection or local ablation. To date, the results of randomized clinical trials testing adjuvant therapy in patients with HCC have been
negative. This major unmet need has been addressed with the IMbrave 050 trial, demonstrating a recurrence-free survival benefit in patients
with a high risk of relapse after resection or local ablation who received adjuvant atezolizumab plus bevacizumab. In parallel, studies testing
neoadjuvant ICIs alone or in combination in patients with early stage disease have also reported efficacy. In this Review, we provide a
comprehensive overview of the current approaches to manage patients with early stage HCC. We also describe the tumour immune
microenvironment and the mechanisms of action of ICIs and cancer vaccines in this setting. Finally, we summarize the available evidence
from phase II/III trials of neoadjuvant and adjuvant approaches and discuss emerging clinical trials, identification of biomarkers and
clinical trial design considerations for future studies.

(Josep M. Llovet et. Al. – nature reviews clinical oncology – February 2024)

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