Piao Mingjian, Li Chengjie, Huang Ziyue, Zhang Nan, Li Jiongyuan, Yang Xu, Li Shuofeng, Wang Shanshan, Xun Ziyu, Zhang Longhao, Sun Boyu, Zhang Ting, Yang Xiaobo, Zhao Haitao
Department of Liver Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Liver Cancer. 2025 Feb 13;14(4):456-473. doi: 10.1159/000543994. eCollection 2025 Aug.
INTRODUCTION: Hepatocellular carcinoma (HCC) has a high incidence rate and is often asymptomatic in its early stages. Combination therapies using immune checkpoint inhibitors (ICIs) have demonstrated survival benefits and high objective response rates, offering hope for conversion surgery in patients with initially unresectable HCC. We aimed to investigate the oncological outcomes of conversion surgery compared to those with continuing systemic treatment alone in patients who responded well to ICI-based therapy, as well as the surgical outcomes associated with conversion surgery. METHODS: We consecutively enrolled patients diagnosed with HCC between January 1, 2019, and February 1, 2024. These patients received treatment with ICIs combined with either anti-vascular endothelial growth factor antibodies or tyrosine kinase inhibitors. Tumor response and resectability were assessed every 2 months. Patients who responded positively and met the criteria for conversion surgery were included. RESULTS: Among 613 patients with initially unresectable HCC, 128 achieved conversion and met the surgical resection criteria during combination therapy. Of these, 54 continued nonsurgical comprehensive treatment, 74 underwent conversion surgery, and 57 continued their original treatment post-surgery. The median follow-up time was 24.1 and 42.5 months for the surgery and non-surgery groups, respectively. The median progression-free survival (PFS) was 29.4 months in the surgery group versus 11.2 months in the non-surgery group ( < 0.0001, hazard ratio [HR] = 0.39 [0.24-0.63]). The median OS was not reached in the surgery group, compared to 25.4 months in the non-surgery group ( < 0.0001, HR = 0.26 [0.14-0.46]). Multivariate Cox regression analysis indicated that conversion surgery was independently associated with improved OS and PFS ( < 0.001), and continuing the original treatment post-surgery significantly influenced OS and recurrence-free survival. CONCLUSION: Conversion surgery after meeting the surgical criteria during immunotherapy provides significant prognostic benefits for patients with initially unresectable HCC, demonstrating high safety and R0 resection rates. For those undergoing conversion surgery, promptly resuming the original treatment after surgery is necessary.
引言：肝细胞癌（HCC）发病率高，早期常无症状。使用免疫检查点抑制剂（ICI）的联合疗法已显示出生存获益和高客观缓解率，为初始不可切除的HCC患者的转化手术带来了希望。我们旨在研究在对基于ICI的治疗反应良好的患者中，转化手术与单纯继续全身治疗相比的肿瘤学结局，以及与转化手术相关的手术结局。 方法：我们连续纳入了2019年1月1日至2024年2月1日期间诊断为HCC的患者。这些患者接受了ICI联合抗血管内皮生长因子抗体或酪氨酸激酶抑制剂的治疗。每2个月评估一次肿瘤反应和可切除性。纳入反应阳性且符合转化手术标准的患者。 结果：在613例初始不可切除的HCC患者中，128例在联合治疗期间实现了转化并符合手术切除标准。其中，54例继续非手术综合治疗；74例接受了转化手术；57例术后继续原治疗。手术组和非手术组的中位随访时间分别为24.1个月和42.5个月。手术组的中位无进展生存期（PFS）为29.4个月，非手术组为11.2个月（<0.0001，风险比[HR]=0.39[0.24 - 0.63]）。手术组的中位总生存期（OS）未达到，非手术组为25.4个月（<0.0001，HR = 0.26[0.14 - 0.46]）。多因素Cox回归分析表明，转化手术与OS和PFS的改善独立相关（<0.001），术后继续原治疗对OS和无复发生存期有显著影响。 结论：免疫治疗期间达到手术标准后的转化手术为初始不可切除的HCC患者提供了显著的预后益处，显示出高安全性和R0切除率。对于接受转化手术的患者，术后及时恢复原治疗是必要的。
Cochrane Database Syst Rev. 2018-2-6
Nat Rev Clin Oncol. 2024-4
Nat Rev Immunol. 2024-4
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