PERIOPERATIVE immunotherapy in hepatocellular carcinoma demonstrates improved event free survival in patients undergoing surgical resection, offering a promising strategy to reduce recurrence risk in high-risk disease.
Perioperative Immunotherapy in Hepatocellular Carcinoma
Surgical resection remains the primary curative approach for patients with hepatocellular carcinoma, yet long term outcomes remain poor, with five-year recurrence rates exceeding 60–70%. Recurrence continues to be the leading cause of mortality, highlighting the urgent need for effective perioperative strategies.
Previous attempts to improve outcomes using adjuvant systemic therapies have not demonstrated clear benefit, including immune checkpoint inhibitor regimens that failed to significantly improve recurrence free survival.
Recent interest has focused on perioperative immunotherapy, integrating both preoperative and postoperative treatment. This approach aims to enhance immune priming before surgery while maintaining antitumour activity after tumour removal.
The CARES-009 trial evaluated this concept in patients with resectable hepatocellular carcinoma at intermediate or high risk of recurrence.
CARES-009 Trial Findings
The multicentre, open label, randomised phase II/III trial enrolled patients across 16 hospitals in China. Participants received either perioperative camrelizumab combined with rivoceranib or surgery alone. The treatment strategy included neoadjuvant immunotherapy followed by surgery and up to one year of adjuvant therapy.
The primary endpoint of event free survival was met, with the experimental arm demonstrating a significant benefit compared with surgery alone: hazard ratio: 0.63; 37% relative risk reduction. This improvement was observed despite a relatively short median systemic treatment duration of approximately 6 months.
However, interpretation of event free survival is complex, as it includes perioperative events beyond tumour recurrence and may be influenced by treatment delays or discontinuation.
Clinical Implications and Future Directions
The findings suggest that perioperative immunotherapy may provide clinically meaningful benefit in a population with biologically aggressive yet resectable disease. By combining immune checkpoint inhibition with anti-angiogenic therapy, the strategy aims to enhance immune activation, improve tumour infiltration by lymphocytes, and sustain postoperative immune surveillance.
Notably, 38% of patients experienced grade 3 or higher treatment related adverse events, although this rate remains lower than that reported in advanced disease settings (80%). While a high proportion of patients discontinued adjuvant therapy (86%), relatively few did so due to toxicity (15%), suggesting other contributing factors such as disease characteristics and treatment duration.
Although overall survival data are not yet available, the improvement in event free survival provides an important early signal of efficacy.
These results support further investigation of perioperative immunotherapy in hepatocellular carcinoma, with emphasis on optimising patient selection, refining treatment duration, and adapting strategies to broader clinical settings.
Reference
Aceituno L et al. Perioperative immunotherapy to reduce recurrence in resectable hepatocellular carcinoma – lessons learned from the CARES-009 trial. JHEP Rep. 2026:101820; doi: 10.1016/j.jhepr.2026.101820.
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