Hepatocellular Carcinoma Over Three Decades: from Screening Evolution to Integrated Therapeutic Strategies

Hepatocellular carcinoma (HCC) continues to impose a substantial global health burden, with the incidence and the mortality remaining closely aligned despite major advances in diagnostics and therapeutics. Over the past three decades, screening and treatment technologies have evolved from single-marker surveillance to risk-stratified, multimodal assessment, and from standalone local therapies to integrated radiologic and immunologic strategies. However, these innovations have not translated into proportional population-level benefits, as early detection rates remain persistently low across many regions. This review provides a comprehensive synthesis of the three-decade evolution in HCC surveillance and treatment, highlighting how biomarker innovation, imaging standardization, and emerging systemic therapies have reshaped clinical practice, while identifying key barriers that continue to limit real-world impact, including metabolic disease-related imaging challenges, inconsistent long-term surveillance adherence, and pronounced disparities in healthcare access. By integrating epidemiologic trends, clinical evidence, and technological advances, this review emphasizes a central principle: meaningful improvement in HCC outcomes depends less on the availability of sophisticated tools than on the timely identification and management of patients within the curative window. The insights presented aim to develop future precision-based, equitable, and multimodal strategies for HCC prevention and control.