Recently, Deputy Director Dr. Zhao Haitao and Associate Chief Physician Dr. Yang Xiaobo's team from the Department of Liver Surgery, PUMCH published significant research findings in the prestigious journal Liver Cancer (a tier 1 journal, ranked among the top 5% by the Chinese Academy of Sciences, IF=11.6) as Research Article. Through a retrospective cohort study, the research team demonstrated that for patients with initially unresectable and intermediate- to advanced-staged hepatocellular carcinoma (HCC), implementing conversion surgery following immune checkpoint inhibitor (ICI)-based combination therapy significantly extends patient survival with favorable safety profiles. This discovery confirms the essential role of surgery in comprehensive HCC treatment and provides critical evidence for well-defined conversion therapy implementation.
HCC is among the most common malignancies worldwide, characterized by insidious onset and rapid progression. Approximately 70% of patients are diagnosed at intermediate-to-advanced stages, presenting with diffuse tumors, major vascular invasion, or compromised liver function—conditions traditionally considered inoperable. While targeted therapies, chemoradiotherapy, and combination immunotherapy, among other approaches, can extend survival in some patients at intermediate-to-advanced stages, objective response rates remain below 40%. The Liver Surgery team at PUMCH, with extensive expertise in comprehensive hepatobiliary tumor management, discovered that conversion surgery could benefit these patients. Conversion surgery involves performing surgical resection after patients initially deemed unsuitable for radical surgery achieve significant tumor regression and meet surgery criteria through systemic treatments such as chemotherapy, targeted therapy, or immunotherapy. The goal of conversion therapy is to eliminate potentially drug-resistant cancer cells and preserve the therapeutic benefits from systemic treatment, thereby improving survival rates and treatment outcomes. However, key questions remained: Does conversion surgery offer survival benefits compared to continued non-surgical systemic treatment? And how safe is conversion surgery?
To address these questions, the Liver Surgery team analyzed 128 patients with initially unresectable HCC treated between 2019 and 2024. After receiving at least two cycles of ICI-based combination therapy, all patients met conversion surgery criteria. Among them, 74 patients underwent conversion surgery, while 54 continued non-surgical treatment. The research team collected and compared comprehensive data from both groups to evaluate conversion surgery's clinical value.
Results revealed that the surgery group achieved progression-free survival of 29.4 months, with the three-year overall survival rate approaching 80%. Remarkably, over half of the surgical patients remained recurrence-free for four years, suggesting potential clinical cure. In contrast, the non-surgery group showed progression-free survival of only 11.2 months and median overall survival of 25.4 months. The results demonstrated statistically significant efficacy differences between the two groups.
Cox regression analysis indicated that patients who continued their original effective ICI-based combination therapy after conversion surgery (essentially sequential adjuvant therapy after surgery enabled by neoadjuvant downstaging) experienced further survival extension. Researchers believed that immunotherapy enhances systemic anti-tumor function while surgery eliminates local lesions, a combination that effectively reduces recurrence risk. Throughout treatment, neither group experienced serious adverse reactions, and surgical patients recovered well with no perioperative mortality.
▲Efficacy comparison between the surgery group (red) and the non-surgery group (purple): A. Overall survival (OS) comparison; B. Progression-free survival (PFS) comparison; C. Percentage change in target lesion size from baseline before and after conversion therapy in the surgery group; D. Duration of treatment and outcomes in both patient groups
This large-sample study confirms that conversion surgery significantly improves survival outcomes in patients with initially unresectable HCC, providing scientific evidence for clinical management of these challenging cases. It also signifies a new stage for ICI-based combination plus surgery, advancing from merely "extending survival" toward "potential cure".
Chief Physician Dr. Zhao Haitao explained that the team will next explore optimal drug combinations and treatment durations for conversion therapy, develop molecular markers to predict conversion success and recurrence risk, and conduct multicenter prospective phase III trials to validate the universal applicability of their findings. As conversion surgery becomes more widespread and continues to improve, they hope to give more patients with advanced HCC a fighting chance of survival.
Written by Piao Mingjian and Gan Dingzhu