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[微卫星高度不稳定晚期结直肠癌的免疫治疗]

[Immunotherapy for microsatellite-instability-high advanced colorectal cancer].

作者信息

Ding P R

机构信息

Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China.

出版信息

Zhonghua Wei Chang Wai Ke Za Zhi. 2022 Mar 25;25(3):199-204. doi: 10.3760/cma.j.cn441530-20220118-00025.

Abstract

Microsatellite instability-high (MSI-H) colorectal cancer accounts for approximately 10%-15% of all colorectal cancer patients, while in metastatic diseases the MSI-H population accounts for only 5% of patients. Previous studies have shown that early-stage MSI-H colorectal cancer patients have a good prognosis, but those with advanced disease have a poor prognosis and are not sensitive to chemotherapy. The advent of PD-1 antibodies has significantly improved the prognosis and changed treatment landscape in this population, not only achieving good outcomes in late-line therapy, but also significantly outperforming traditional chemotherapy combined with targeted therapy in first-line therapy. How to overcome primary and secondary drug resistance is a key issue in improving the outcome of MSI-H metastatic colorectal cancer, and commonly used approaches include changing chemotherapy regimens, combining with other immunotherapies, combining with anti-angiogenesis, and local treatments (surgery, radiotherapy, or interventional therapy). It is worth noting that immunotherapy has certain lifelong or even lethal toxicity, and the indications for neoadjuvant immunotherapy must be evaluated with caution. Neoadjuvant immunotherapy in MSI-H advantaged population can achieve high rates of pathological complete remission (pCR) and clinical complete remission (cCR). Therefore, for MSI-H patients with a strong intention to preserve anal sphincter and a strict evaluation of cCR after neoadjuvant immunotherapy, the Watch-and-Wait strategy offers an opportunity to preserve sphincter function and improve long-term survival quality in a subset of mid-to-low rectal cancers. Research on adjuvant immunotherapy in the field of colorectal cancer is also in full swing, and the results are worth waiting for.

摘要

微卫星高度不稳定(MSI-H)的结直肠癌约占所有结直肠癌患者的10%-15%,而在转移性疾病中,MSI-H人群仅占患者的5%。既往研究表明,早期MSI-H结直肠癌患者预后良好,但晚期患者预后较差且对化疗不敏感。PD-1抗体的出现显著改善了该人群的预后并改变了治疗格局,不仅在晚期治疗中取得了良好疗效,而且在一线治疗中也明显优于传统化疗联合靶向治疗。如何克服原发性和继发性耐药是改善MSI-H转移性结直肠癌治疗效果的关键问题,常用方法包括更改化疗方案、联合其他免疫疗法、联合抗血管生成以及局部治疗(手术、放疗或介入治疗)。值得注意的是,免疫治疗具有一定的终身甚至致命毒性,新辅助免疫治疗的适应证必须谨慎评估。MSI-H优势人群的新辅助免疫治疗可实现较高的病理完全缓解(pCR)和临床完全缓解(cCR)率。因此,对于有强烈保肛意愿且新辅助免疫治疗后严格评估cCR的MSI-H患者,观察等待策略为一部分中低位直肠癌患者保留括约肌功能和提高长期生存质量提供了机会。结直肠癌领域的辅助免疫治疗研究也在如火如荼地进行,结果值得期待。

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