Surgery vs. Watch-and-Wait Strategy in Complete Responders for Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer. Some people with HCC have no visible active tumor on imaging after receiving anticancer treatment. This is called a radiologic complete response (rCR). However, imaging cannot always show whether small amounts of living cancer remain. It is not known whether these patients benefit more from surgery to remove the original tumor area or from continuing their current drug treatment without surgery. The purpose of this study is to compare two treatment strategies for adults with HCC who have a confirmed rCR and are considered able to undergo surgery intended to completely remove the tumor. About 60 participants will be randomly assigned in equal numbers to one of two groups. Participants in the surgical resection group will undergo liver surgery and, if they recover adequately, restart the same systemic anticancer treatment they were receiving before randomization approximately 4 to 8 weeks after surgery. Participants in the maintenance therapy group will continue the same systemic anticancer treatment without surgery. The systemic treatment consists of an immune checkpoint inhibitor combined with a targeted or anti-angiogenic drug. Participants in both groups may stop systemic anticancer treatment if they meet all study-defined stopping criteria for at least 24 weeks and a multidisciplinary medical team agrees that treatment can be stopped. Participants will continue to receive imaging examinations, laboratory tests, safety assessments, and quality-of-life assessments during and after treatment. The main study measure is the length of time from randomization until the cancer returns or worsens, or the participant dies from any cause. The study will also evaluate overall survival, side effects and surgical complications, the ability to stop treatment, survival without anticancer treatment, quality of life, findings from surgically removed tissue, and blood-based tumor markers.

Inclusion Criteria: * Voluntary participation and provision of written informed consent. * Age 18 to 80 years, inclusive. * HCC confirmed by histology or cytology or diagnosed according to accepted clinical diagnostic criteria. Histologic or cytologic confirmation is generally required for participants without cirrhosis. * No definite extrahepatic metastasis before initiation of the anticancer treatment that resulted in the current radiologic complete response (rCR). * Previous treatment with a PD-1/PD-L1 inhibitor combined with a targeted or anti-angiogenic agent, with or without locoregional treatment such as transarterial chemoembolization, hepatic arterial infusion chemotherapy, radiotherapy, or ablation. * Continued use of the same systemic regimen between the first documented rCR and confirmatory imaging. Dose modification or temporary interruption for toxicity is permitted, but changing treatment because of insufficient efficacy is not permitted. * rCR confirmed according to mRECIST by repeat imaging performed 4 to 8 weeks after the first documented rCR. * Multidisciplinary team assessment confirming that curative-intent liver resection is medically and technically feasible, R0 resection is expected to be achievable, and perioperative risk is acceptable. * Child-Pugh class A and indocyanine green retention rate at 15 minutes (ICG R15) \=40% of standard liver volume (SLV) for participants with chronic liver disease, substantial hepatic parenchymal injury, or cirrhosis, and generally \>=30% of SLV for participants without substantial fibrosis or cirrhosis. * Pretreatment tumor thrombus involving the portal vein, hepatic vein, and/or inferior vena cava is permitted, but atrial tumor thrombus is not permitted. Previously present macrovascular tumor thrombus must show no definite radiologic activity after treatment and must be considered completely resectable by the multidisciplinary team. * No extrahepatic metastasis or other active HCC lesion on contrast-enhanced CT and/or MRI of the chest, abdomen, and pelvis before randomization. * Eastern Cooperative Oncology Group performance status of 0 or 1. * Adequate organ function before randomization, including: * Hemoglobin \>=90 g/L; * Absolute neutrophil count \>=1.5 x 10\^9/L; * Platelet count \>=60 x 10\^9/L; * Total bilirubin \