New horizons in liver transplantation for hepatocellular carcinoma

Primary liver cancer was the third most common cause of death due to cancer worldwide in 2020. As the predominant type, hepatocellular carcinoma (HCC) represents the overwhelming majority of newly diagnosed primary liver tumours. Liver transplantation remains the treatment of choice for a cure in otherwise unresectable HCC. For nearly thirty years, the Milan and Barcelona Clinic Liver Cancer (BCLC) criteria have guided physicians' clinical decision-making for selection of liver transplant candidates in the treatment of HCC. More recently, studies have demonstrated survival benefit for patients transplanted beyond Milan criteria. This remains an area of active research and includes advancements in local-regional therapies and their role in downstaging tumours to within transplant criteria as a bridge to transplant. Other advancements on the horizon include the identification of tumour biomarkers that may lead to earlier diagnosis and more accurate prediction of prognosis and risk of recurrence, as well as new neoadjuvant therapies and post-transplant immunosuppression regimens that may allow for further expansion of transplant eligibility criteria. Additionally, several recent studies have investigated the potential survival benefit of combination therapy using local-regional intervention with systemic immunotherapy to downstage otherwise unresectable disease that is beyond Milan criteria. Liver transplantation will continue to play an important role in the treatment of HCC for the foreseeable future and based on currently available evidence, both local-regional therapies and immunomodulation in combination are poised to change the landscape of liver transplantation for HCC as we currently know it.