Sequential surgery after conversion therapy for advanced hepatocellular carcinoma: Evidence, controversies, and perspectives

Hepatocellular carcinoma (HCC) often has an insidious onset. Therefore, most patients with HCC are diagnosed at intermediate-to-advanced stages, and upfront radical resection cannot be performed. Systemic regimens that combine immune checkpoint inhibitors (ICIs) with antiangiogenic targeted drugs (AATDs) have established conversion therapy followed by sequential surgery as an important research direction for initially unresectable HCC. The aim of conversion therapy is not only to achieve radiographic response and technical resectability but also to reduce tumor viability, identify patients with favorable tumor biology, and gain durable oncologic benefit. Current evidence supports the combination of ICIs and AATDs as the backbone of conversion therapy, with locoregional therapies, including transarterial chemoembolization, hepatic arterial infusion chemotherapy, and stereotactic body radiotherapy, selectively integrated to address heavy intrahepatic tumor burden, control macrovascular thrombus, or treat residual viable lesions. The decision to proceed with sequential surgery should be made after a successful conversion is confirmed by a multidisciplinary evaluation incorporating tumor necrosis, hepatic functional reserve, future liver remnant volume, overall condition, perioperative drug-related risks, and patient preference. This review focuses on identifying the conversion-specific information required to guide surgical decision-making. Additionally, this study aimed to evaluate conversion rate, R0 resection, pathological response, and postoperative outcomes, explain why high objective response rates may not translate into improved postoperative survival, and provide a practical framework integrating tumor biology, hepatic reserve, perioperative risk, and patient preference.