Orhan Adile, Justesen Tobias F, Raskov Hans, Qvortrup Camilla, Gögenur Ismail
Department of Surgery, Center for Surgical Science, Zealand University Hospital, Køge, Denmark.
Department of Clinical Oncology, Rigshospitalet, Copenhagen, Denmark.
Ann Surg. 2025 Jan 1;281(1):95-104. doi: 10.1097/SLA.0000000000006443. Epub 2024 Jul 15.
To give surgeons a review of the current and future use of neoadjuvant immunotherapy in patients with localized colorectal cancer (CRC).
Immunotherapy has revolutionized the standard of care in oncology and improved survival outcomes in several cancers. However, the applicability of immunotherapy is still an ongoing challenge. Some cancer types are less responsive to immunotherapy, and the heterogeneity in responses within cancer types is poorly understood. Clinical characteristics of the patient, the timing of immunotherapy in relation to surgery, diversities in the immune responses, clonal heterogeneity, different features of the tumor microenvironment, and genetic alterations are some factors among many that may influence the efficacy of immunotherapy.
In this narrative review, we describe the major types of immunotherapy used to treat localized CRC. Furthermore, we discuss the prediction of response to immunotherapy in relation to biomarkers and radiologic assessment. Finally, we consider the future perspectives of clinical implications and response patterns, as well as the potential and challenges of neoadjuvant immunotherapy in localized CRC.
Establishing mismatch repair (MMR) status at the time of diagnosis is central to the potential use of neoadjuvant immunotherapy, in particular immune checkpoint inhibitors, in localized CRC. To date, efficacy is primarily seen in patients with deficient MMR status and polymerase epsilon mutations, although a small group of patients with proficient MMR does respond. In conclusion, neoadjuvant immunotherapy shows promising complete response rates, which may open a future avenue of an organ-sparing watch-and-wait approach for a group of patients.
为外科医生综述新辅助免疫疗法在局部结直肠癌（CRC）患者中的当前及未来应用情况。
免疫疗法彻底改变了肿瘤学的治疗标准，并改善了多种癌症的生存结局。然而，免疫疗法的适用性仍是一个持续存在的挑战。一些癌症类型对免疫疗法反应较差，且癌症类型内反应的异质性仍未得到充分理解。患者的临床特征、免疫疗法与手术的时间关系、免疫反应的多样性、克隆异质性、肿瘤微环境的不同特征以及基因改变等诸多因素都可能影响免疫疗法的疗效。
在本篇叙述性综述中，我们描述了用于治疗局部CRC的主要免疫疗法类型。此外，我们讨论了与生物标志物和影像学评估相关的免疫疗法反应预测。最后，我们考虑了临床意义和反应模式的未来前景以及新辅助免疫疗法在局部CRC中的潜力和挑战。
在诊断时确定错配修复（MMR）状态对于新辅助免疫疗法（尤其是免疫检查点抑制剂）在局部CRC中的潜在应用至关重要。迄今为止，疗效主要见于MMR缺陷状态和聚合酶ε突变的患者，尽管一小部分MMR proficient（原文有误？应为proficient MMR，即错配修复功能正常）的患者也有反应。总之，新辅助免疫疗法显示出有望达到的完全缓解率，这可能为一组患者开辟未来保留器官的观察等待方法的途径。
