在肝细胞癌（HCC）治疗迈入免疫联合时代的浪潮中，系统联合局部治疗策略正经历着从量变到质变的重构。2026年7月3日至5日，第十六届亚太原发性肝癌专家会议（APPLE 2026）在上海隆重召开。大会汇聚亚太、欧美等多个国家肝癌领域顶尖专家，探讨肝癌防治新策略。会上，日本近畿大学Masatoshi Kudo教授针对免疫联合时代下的肝癌系统联合局部治疗策略进行了专题报告，引发广泛关注。借此次大会契机，《肿瘤瞭望》特邀请Kudo教授进行了独家专访。Kudo教授结合EMERALD-3等突破性数据，不仅厘清了当前“系统+局部”治疗的证据链，更针对临床关切的TACE适用人群拓展以及“长疾病进展后生存（Post-progression survival，PPS）时代”的OS终点评判等关键问题，给出了务实且具有前瞻性的答案，勾勒出未来肝癌治疗进化的清晰路径。
编者按：在肝细胞癌（HCC）治疗迈入免疫联合时代的浪潮中，系统联合局部治疗策略正经历着从量变到质变的重构。2026年7月3日至5日，第十六届亚太原发性肝癌专家会议（APPLE 2026）在上海隆重召开。大会汇聚亚太、欧美等多个国家肝癌领域顶尖专家，探讨肝癌防治新策略。会上，日本近畿大学Masatoshi Kudo教授针对免疫联合时代下的肝癌系统联合局部治疗策略进行了专题报告，引发广泛关注。借此次大会契机，《肿瘤瞭望》特邀请Kudo教授进行了独家专访。Kudo教授结合EMERALD-3等突破性数据，不仅厘清了当前“系统+局部”治疗的证据链，更针对临床关切的TACE适用人群拓展以及“长疾病进展后生存（Post-progression survival，PPS）时代”的OS终点评判等关键问题，给出了务实且具有前瞻性的答案，勾勒出未来肝癌治疗进化的清晰路径。
01
《肿瘤瞭望》：从您开创的靶向联合TACE到如今的免疫联合LRT，您认为“系统+局部”这一治疗模式最核心的质变是什么？
Masatoshi Kudo 教授：回顾TKI时代，我们确实经历了一段探索的瓶颈期。当年那五项关键研究——无论是索拉非尼联合TACE，还是索拉非尼联合布立尼布或奥兰替尼——均未能如愿达到主要终点。不过，TACTICS研究是个例外，它不仅达成了延长PFS的主要终点，更为我们带来了具有临床意义的OS获益，为后续的联合策略提供了重要启示。
然而，免疫治疗的问世真正重塑了格局。以阿替利珠单抗联合贝伐珠单抗为代表，或其他ICI联合抗VEGF/TKI的方案，展现出了TKI单药难以企及的缩瘤能力。这种强效的肿瘤退缩，不仅大幅提升了TACE实现完全缓解（CR）的概率，更重要的是，它为我们打开了转化治疗的大门——让原本不可切除的肿瘤转化为可切除，让根治性手术成为可能。这无疑是相较于TKI时代，肝癌治疗领域最具里程碑意义的跨越。
During the TKI era, we encountered significant challenges; five pivotal trials—including sorafenib plus TACE, sorafenib plus brivanib, and sorafenib plus orantinib—all failed to meet their primary endpoints. The exception was the TACTICS trial, which successfully met its primary endpoint by prolonging PFS and demonstrated a clinically meaningful OS benefit.
However, the landscape has been fundamentally reshaped by immunotherapy. Regimens like atezolizumab plus bevacizumab, or other ICI combinations with anti-VEGF TKIs, achieve something single-agent TKIs could never accomplish: significant tumor shrinkage. This profound reduction in tumor volume not only facilitates complete response with TACE but, crucially, enables conversion therapy—making curative surgery possible for initially unresectable patients. This shift from mere disease control to tumor eradication represents the most significant advancement over the TKI era.
02
《肿瘤瞭望》：面对多种LRT手段和强效靶免药物的组合，例如EMERALD-3研究所展示的，我们如何判断哪位患者真正需要二联或三联的治疗策略？未来能否依据生物学标志物来定制“最小有效”的方案？
Masatoshi Kudo 教授：双免疫疗法目前的获批适应证主要针对晚期肝细胞癌（HCC），特别是伴有血管侵犯或肝外转移的患者。因此，单纯双免疫方案并不适用于TACE适应证人群。但对于适合TACE的患者，双免疫联合TACE则是重要的治疗选择。EMERALD-3研究尽管属于探索性质，但其结果非常明确：双免疫联合TACE在数值上显著延长了PFS和OS。此外，双免疫联合仑伐替尼同样展现了显著的PFS和OS获益。这些数据极具临床价值。
值得注意的是，我对适应证的界定有不同的看法。即便是晚期HCC，只要排除了VP3或VP4级的门静脉主干癌栓，即便存在肝外转移，TACE本身仍是一个强有力的预后影响因素。这类患者其实也属于适合TACE的人群。因此，我认为在未来，对于部分晚期HCC患者，双免疫联合TACE同样具有重要的应用前景。
Dual IO combinations are currently indicated for advanced-stage HCC, specifically in patients presenting with vascular invasion or extrahepatic spread. Consequently, IO plus IO as a monotherapy regimen is not intended for patients who are TACE-eligible. However, for this specific TACE-eligible population, the combination of dual IO plus TACE represents a viable strategy. The EMERALD-3 trial, through its pre-planned exploratory analysis, provided compelling evidence: while exploratory in nature, the data clearly demonstrated a nominally significant prolongation of both PFS and OS with the dual IO plus TACE approach. Furthermore, the combination of dual IO plus lenvatinib has also yielded significant survival benefits.
These findings are crucial. In my view, the definition of TACE-eligibility should be broader. Even among patients with advanced HCC and extrahepatic spread—provided we exclude those with Vp3 or Vp4 portal vein invasion—TACE remains a powerful prognostic modifier. Therefore, I believe that in the future, dual IO plus TACE will be indicated not just for intermediate stages, but potentially for a selected subset of advanced HCC patients with extrahepatic spread.
03
《肿瘤瞭望》：展望未来的3-5年，您认为在“局部+系统”治疗领域，最亟待解决的科学问题是什么？
Masatoshi Kudo 教授：是的，中间期或所谓“适合TACE”的人群，其肿瘤负荷实际上介于BCLC A/B期与典型晚期C期之间，较后者要轻一些。EMERALD-3研究的数据非常振奋人心：在双免疫（STRIDE方案）联合仑伐替尼再加TACE的队列中，中位总生存期（OS）达到了约40个月，这与传统晚期患者约20个月的生存数据形成了鲜明对比。
目前来看，双免疫联合TACE或其他免疫+抗VEGF/TKI的联合方案，在延长PFS方面已获证实，且在OS上也呈现出显著的改善趋势。虽然由于交叉治疗和后续有效药物的存在，要在统计学上确证OS的显著差异变得愈发困难——毕竟试验结束后，无论试验组还是对照组，患者在进展后都能接受到非常有效的序贯治疗，这使得PPS被大大拉长，稀释了前期治疗的OS差异。
因此，我认为在目前的研究环境下，OS呈现出的这种改善趋势本身就极具临床意义，不必过分纠结于P值是否跨过阈值。这才是我们在解读当代肝癌临床试验数据时，最需要厘清的关键问题。
Indeed, when we look at the intermediate-stage or TACE-eligible population—drawing from BCLC A, B, and even select C patients—their tumor burden is generally lower than that of typical advanced-stage HCC. The EMERALD-3 data is striking: with the STRIDE regimen plus lenvatinib and TACE, the median OS reaches approximately 40 months. This is a substantial improvement compared to the roughly 20-month median OS we typically see in unselected advanced-stage populations.
While dual IO plus TACE, or other IO plus anti-VEGF/TKI combinations, have clearly demonstrated PFS benefits and a strong trend toward better OS, proving statistical significance for OS has become challenging. Due to the availability of highly effective subsequent therapies post-progression—both in the experimental and control arms—post-progression survival (PPS) is now remarkably long. This prolonged PPS tends to dilute the OS difference between arms.
Therefore, I believe that demonstrating a positive trend in OS is clinically sufficient in the modern era. Over-emphasizing statistical significance for OS in the face of such long PPS is misleading. This is perhaps the most critical nuance we must consider when interpreting current trial data.
Masatoshi Kudo 教授
日本近畿大学医学院胃肠病学和肝脏病学系主任
国际肝癌协会（ILCA）创始理事、理事
亚太原发性肝癌专家（APPLE）会议主席（2015-2017）
美国肝脏疾病研究协会（AASLD）肝胆恶性肿瘤特别兴趣小组指导委员会成员
日本肝癌指南编委会主席
Liver Cancer杂志主编