Navigating the landscape of liver cancer management: Study designs in clinical trials and clinical practice

Abstract

Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer death worldwide and its prognosis is highly heterogeneous, being related not only to tumour burden but also to the severity of underlying chronic liver disease. Moreover, advances in systemic therapies for HCC have increased the complexity of patient management. Randomised-controlled trials represent the gold standard for evidence generation across all areas of medicine and especially in the oncology field, as they allow for unbiased estimates of treatment effect without confounders. Observational studies have many problems that could reduce their internal and external validity. However, large prospective (well-conducted) observational real-world studies can detect rare adverse events or monitor the occurrence of long-term adverse events. How best to harness real world data, which refers to data generated from the routine care of patients, and real-world 'evidence', which is the evidence generated from real-world data, represents an open challenge. In this review article, we aim to provide an overview of the benefits and limitations of different study designs, particularly focusing on randomised-controlled trials and observational studies, to address important and not fully resolved questions in HCC research.

Keywords: Hepatocellular Carcinoma; Overall Survival; Progression-free survival; Randomised-controlled trial; Recurrence-free Survival; adjuvant therapy; immunotherapy; observational study; systemic therapy; time-to-progression; time-to-recurrence.