| Sumario: | Simple Summary: Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and is frequently diagnosed at advanced stages, which are generally unsuitable for curative interventions. Among patients who undergo liver resection, approximately 70% experience relapse within five years. Unlike other older therapies, immunotherapy uses Immune Checkpoint Inhibitors (ICIs) to stimulate the body's immune system to recognize and attack cancer cells. While clinical trials investigating neoadjuvant, perioperative, and adjuvant immunotherapy have demonstrated encouraging preliminary outcomes, the use of these approaches in HCC remains controversial, as they are still considered investigational. This narrative review aims to summarize the current role of immunotherapy in the management of HCC amenable to surgical treatment with curative intent, highlighting recent clinical trial results. Additionally, emerging directions involving novel immunotherapy targets are discussed. Hepatocellular carcinoma (HCC) is the most common primary liver cancer and is frequently diagnosed at advanced stages, thereby limiting curative treatment options. Although interventions with curative intent, such as liver resection and ablation, are available, recurrence rates exceed 70%. Recent developments in HCC management have shifted the focus from conventional surgery and targeted therapies to immunotherapy. This review synthesizes current evidence on immunotherapy for curative purposes in HCC, including both neoadjuvant and adjuvant strategies. It evaluates completed and ongoing clinical trials of immune checkpoint inhibitors (ICIs), administered as monotherapy or in combination with anti-angiogenic agents or dual-checkpoint blockade. ICIs may transform the initial treatment paradigm for advanced HCC, although their applications remain in the investigational stage. Preliminary results from the IMbrave050 trial suggested that adjuvant immunotherapy following radical liver resection improves recurrence-free survival (RFS) in high-risk patients. However, the initially promising outcomes of the combination of atezolizumab and bevacizumab compared with active surveillance were not sustained in the median follow-up, and long-term survival results are awaited. Although several studies have demonstrated encouraging preliminary results, a clear survival benefit has not yet been established. Further studies are necessary to establish definitive conclusions. Immunotherapy has a pathophysiological basis and preliminary evidence to redefine HCC management across disease stages; its integration into pre- and post-operative strategies may increase resectability, reduce recurrence, and improve survival. Ongoing trials are expected to clarify its exact role.
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