Wang Y, Tian F, Jing C Q
Department of Gastrointestinal Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, China.
Zhonghua Wei Chang Wai Ke Za Zhi. 2025 Jun 25;28(6):700-706. doi: 10.3760/cma.j.cn441530-20241114-00373.
Neoadjuvant chemoradiotherapy (NACRT) is the standard treatment for locally advanced rectal cancer (LARC), yet the pathological complete response (pCR) rates remain suboptimal. The introduction of immunotherapy has opened new avenues for LARC management, particularly in patients with mismatch repair deficiency (dMMR) or microsatellite instability-high (MSI-H) status. In this subset, anti-programmed cell death protein-1 (PD-1) monoclonal antibodies demonstrate marked efficacy, achieving high rates of clinical complete response (cCR) and pCR, thereby facilitating non-operative watch-and-wait (W&W) strategies. However, long-term outcomes and large-scale validation are still awaited. Conversely, in patients with LARC who have proficient mismatch repair (pMMR) or microsatellite stability (MSS), PD-1 inhibition alone shows limited benefit. Current research thus focuses on combinatorial approaches. Combining immunotherapy with chemoradiotherapy has shown promise in improving pCR rates in pMMR/MSS LARC, without significantly exacerbating severe adverse events. However, the discordance between post-treatment imaging assessments and pathological findings complicates clinical decision-making. Future directions include optimizing immune checkpoint inhibitor (ICI) regimens for pMMR/MSS LARC, with ongoing investigations into dual immunotherapy and anti-angiogenic synergism. Additionally, biomarker discovery, which is leveraging multi-omics and artificial intelligence (AI), will be pivotal in achieving precision therapy that balances short-term efficacy with long-term survival benefits.
新辅助放化疗(NACRT)是局部晚期直肠癌(LARC)的标准治疗方法,但其病理完全缓解(pCR)率仍不尽人意。免疫疗法的引入为LARC的治疗开辟了新途径,特别是对于错配修复缺陷(dMMR)或微卫星高度不稳定(MSI-H)状态的患者。在这一亚组中,抗程序性细胞死亡蛋白1(PD-1)单克隆抗体显示出显著疗效,实现了较高的临床完全缓解(cCR)率和pCR率,从而促进了非手术观察等待(W&W)策略。然而,长期结果和大规模验证仍有待观察。相反,在错配修复功能正常(pMMR)或微卫星稳定(MSS)的LARC患者中,单独使用PD-1抑制剂的获益有限。因此,目前的研究集中在联合治疗方法上。免疫疗法与放化疗联合应用在提高pMMR/MSS LARC的pCR率方面已显示出前景,且未显著加重严重不良事件。然而,治疗后影像学评估与病理结果之间的不一致使临床决策变得复杂。未来的方向包括优化pMMR/MSS LARC的免疫检查点抑制剂(ICI)方案,目前正在研究双重免疫疗法和抗血管生成协同作用。此外,利用多组学和人工智能(AI)发现生物标志物对于实现平衡短期疗效和长期生存获益的精准治疗至关重要。