Systemic therapies in advanced hepatocellular carcinoma: How do older patients fare?

Advanced hepatocellular cancer (HCC) is the fourth leading cause of cancer-related death globally and is most common in elderly patients with a peak incidence in the UK at ages 85-89 years. In addition to the well-established risk factors of alcohol and viral hepatitis B and C, rising obesity and associated non-alcoholic fatty liver disease is projected to contribute to increased incidence of advanced HCC in elderly patients. The management of advanced HCC is changing rapidly; for over a decade the multi-kinase inhibitor sorafenib has been the only treatment option that offered a proven survival advantage, but in the last 4 years other treatment options have emerged including other kinase inhibitors, and monoclonal antibodies targeting angiogenesis and immune checkpoint inhibitors. Recent clinical trials have recruited older patients with no maximum age exclusion criteria, and age has not been found to be predictive for treatment effect in subgroup analyses. Chronological age is an unreliable measure of fitness for treatment and frailty may be a more apt descriptor, but the lack of a unified assessment tool has limited its use in current practice. Development of unified frailty assessments and prospective large-scale studies of novel systemic therapies where age and frailty are evaluated would be informative.