肝细胞癌切除术后辅助靶向及免疫治疗的进展

Advances in Adjuvant Targeted and Immunotherapy after Resection of Hepatocellular Carcinoma

摘要: 肝细胞癌切除术后五年复发率仍高达70%，降低复发风险的术后辅助治疗受到持续关注。靶向免疫联合治疗在晚期肝细胞癌中取得不错的效果，但是将此类治疗方案用作术后辅助治疗时收效甚微。本文系统回顾目前有关HCC术后辅助靶向及免疫治疗的主要临床试验之后可见：STORM研究中索拉非尼辅助无生存增益，以KEYNOTE-937为代表的免疫单药III期试验均报出阴性结果，IMbrave050研究(“T + A”方案辅助)早期提示复发风险下降，但随访延展后该趋势未持续，总生存也未改善。相比之下CARES-009试验采用了“新辅助–手术–辅助”的围手术期连续干预模式，中位无事件生存期获得了有统计学意义的延长。综合现有研究，固定疗程的术后辅助方案与肝细胞癌切除术后的特殊复发机制存在矛盾，且单纯依靠临床病理参数来筛选治疗获益人群显然不够合理。因此建议主动建立动态监测体系，以循环肿瘤DNA等指标指导个体化干预，真正做好围手术期管理。

Abstract: The five-year recurrence rate after resection of hepatocellular carcinoma (HCC) remains approximately 70%, and postoperative adjuvant strategies aimed at reducing this risk have drawn sustained attention. Although targeted therapy combined with immunotherapy has demonstrated notable efficacy in advanced HCC, translating such regimens into the adjuvant setting has yielded limited benefit. This review systematically examines major clinical trials evaluating adjuvant targeted and immunotherapeutic approaches following HCC resection. The STORM trial showed no survival advantage for adjuvant sorafenib, and phase III trials of immune checkpoint inhibitor monotherapy—exemplified by KEYNOTE-937—have reported negative results. While early analysis of the IMbrave050 trial (adjuvant atezolizumab plus bevacizumab) suggested a reduction in recurrence risk, extended follow-up revealed that this trend was not maintained and overall survival was not improved. In contrast, the CARES-009 trial, which employed a perioperative continuum of neoadjuvant therapy, surgery, and adjuvant treatment, demonstrated a statistically significant prolongation of median event-free survival. Taken together, current evidence indicates an inherent discordance between fixed-duration postoperative adjuvant regimens and the distinct recurrence biology following HCC resection. Moreover, selection of patients likely to benefit from adjuvant therapy based solely on clinicopathological parameters remains inadequate. It is therefore recommended that dynamic surveillance frameworks be established, incorporating biomarkers such as circulating tumor DNA to guide individualized intervention and to optimize comprehensive perioperative management.