The University of Texas MD Anderson Cancer Center, 1155 Pressler, Unit 1374, Houston, Texas 77030, USA.
Earle A. Chiles Research Institute, Providence Portland Medical Center, 4805 NE Glisan, Suite 2N82, Portland, Oregon 97213, USA.
Nat Rev Urol. 2018 Feb;15(2):112-124. doi: 10.1038/nrurol.2017.190. Epub 2017 Dec 5.
Immunotherapy has been used in localized urothelial carcinoma for decades, especially in the treatment of superficial disease, in which instillation of BCG is a commonly used treatment option. Clinical investigations based on new insights into the immunogenic potential of metastatic urothelial carcinoma have led to the accelerated FDA approval of the immune checkpoint inhibitors atezolizumab, nivolumab, durvalumab, avelumab, and pembrolizumab. Preliminary findings suggest additional benefits of combinations of immunotherapeutic agents as a future treatment approach in metastatic urothelial carcinoma. Treatment experience with immunotherapy suggests that these drugs are associated with a unique spectrum of immune-related adverse events and specific immune-related patterns of response, including cases of pseudoprogression, which could impede the optimal use of immune checkpoint inhibitors in the clinic. Appropriate management of immune-related adverse events and a greater awareness of immune-mediated response patterns will help to inform treatment decisions and improve patient outcomes; predictive biomarkers of response might facilitate selection of patients who are most likely to respond to and benefit from these exciting new treatments.
免疫疗法在局部尿路上皮癌中已应用数十年，尤其适用于治疗表浅疾病，其中 BCG 灌注是一种常用的治疗选择。基于对转移性尿路上皮癌免疫原性潜力的新见解进行的临床研究，促使免疫检查点抑制剂阿替利珠单抗、纳武利尤单抗、度伐鲁单抗、avelumab 和 pembrolizumab 加速获得 FDA 批准。初步研究结果表明，联合免疫治疗药物作为转移性尿路上皮癌的未来治疗方法具有额外益处。免疫治疗的治疗经验表明，这些药物与独特的免疫相关不良事件谱和特定的免疫相关反应模式相关，包括假性进展病例，这可能会阻碍免疫检查点抑制剂在临床中的最佳应用。免疫相关不良事件的适当管理和对免疫介导反应模式的更高认识将有助于为治疗决策提供信息并改善患者预后；对反应的预测性生物标志物可能有助于选择最有可能对这些令人兴奋的新治疗方法产生反应和获益的患者。
