Navigating the complexities: challenges and opportunities in conversion therapy for advanced hepatocellular carcinoma

Primary liver cancer ranks as the sixth most prevalent malignant tumor and stands as the second leading cause of cancer-related mortality globally, posing a significant threat to public health. Hepatocellular carcinoma (HCC) is the most common type of liver cancer worldwide. Surgical resection remains the cornerstone treatment for achieving radical cure and prolonged survival in HCC patients. Contrary to Western countries, the majority of HCC patients in China present with hepatitis B virus infection and consequent liver cirrhosis, with most cases diagnosed at an intermediate or advanced stage. This complexity results in a poor prognosis. Recent advancements in local therapeutic techniques and the introduction of systemic therapies, including targeted and immunotherapy agents, have provided new avenues for both clinical and basic conversion therapy for advanced HCC. Integrating multi-dimensional local and systemic therapies, multi-modal sequential, and comprehensive multidisciplinary approaches into the management of HCC patients has demonstrated promising conversion success rates. This holistic management strategy involves combining multiple treatment modalities vertically and coordinating various disciplines horizontally. However, significant challenges remain, including the precise selection of patients eligible for conversion therapy, the optimal choice of conversion therapy regimens, and the accurate determination of surgical timing post-conversion therapy. Addressing these challenges is crucial for hepatobiliary surgeons. High-quality, randomized controlled trials are urgently needed to generate robust evidence for clinical practice. This review aims to synthesize the latest research developments both in China and internationally and examines key issues in the realm of HCC conversion therapy.