Hepatocellular carcinoma (HCC) management is a challenging task. Despite continuous efforts to develop more effective treatments, patient prognosis often remains poor. Recently, a new management concept-the “multiparametric therapeutic Hierarchy”-has been proposed, with the hypothetical advantage of avoiding the risk of undertreatment inherent in “classical” HCC management modalities while also minimizing the risk of overtreatment that may occur when inexperienced clinicians adopt overly aggressive treatment hierarchies. The “multiparametric” concept emphasizes a more comprehensive evaluation of each patient, focusing on their individual clinical presentation. Among the various factors considered, patient fitness plays a critical role. Here, fitness is understood as the set of patient-specific characteristics that can influence the outcomes of therapies within the hierarchical framework (or even preclude certain therapies altogether). This multifaceted concept extends beyond traditional “Performance Status” measurements, incorporating considerations of frailty and comorbidity. In this review, we explore the available evidence regarding the role of patient fitness within the multiparametric therapeutic hierarchy for HCC. Finally, we discuss fitness considerations across different levels of the therapeutic hierarchy, highlighting current evidence, existing challenges, and limitations, with the aim of providing new insights for physicians involved in HCC management.
