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.

肝癌，特别是肝细胞癌（HCC），是全球第六大常见癌症，也是全球癌症死亡的第三大原因。有效的全身疗法，特别是涉及免疫检查点抑制剂（ICIs）的疗法的开发，大大改善了晚期 HCC 患者的预后。大约 30% 的患者被诊断为早期疾病，目前正在接受潜在的治愈性治疗，例如切除、肝移植或局部消融，从而使中位总生存期超过 60 个月。尽管如此，高达 70% 的患者会在切除或局部消融后 5 年内出现疾病复发。迄今为止，测试 HCC 患者辅助治疗的随机临床试验结果均为阴性。IMbrave 050 试验已经解决了这一未满足的主要需求，证明了接受阿特朱单抗加贝伐单抗辅助治疗的切除或局部消融后复发风险高的患者具有无复发生存获益。与此同时，针对早期疾病患者单独或联合使用新辅助 ICI 的研究也报告了疗效。在这篇综述中，我们全面概述了当前治疗早期 HCC 患者的方法。我们还描述了肿瘤免疫微环境以及 ICI 和癌症疫苗在这种情况下的作用机制。最后，我们总结了新辅助和辅助方法的 II/III 期试验的现有证据，并讨论了新兴的临床试验、生物标志物的识别以及未来研究的临床试验设计注意事项。