Abstract

From 2016 through the present day, we have witnessed extraordinarily rapid advances and regulatory approvals of immune checkpoint inhibitors targeting the PD-1/PD-L1 pathway, which has significantly improved survival among patients with advanced and metastatic urothelial carcinoma (mUC). Although these agents usually are well tolerated, their unique mechanism of action may enhance cytotoxic T-cell mediated immunity, evoking unique side effects that differ from conventional chemotherapy or molecularly targeted agents. The most common immune-related adverse events (irAEs) are dermatitis, colitis, pneumonitis, thyroid dysfunction, and transaminitis, but any organ system permeated by the lymphatic vasculature can be affected; also, neuropathies and arthralgias may occur. Immune-mediated events of any grade require prompt recognition and appropriate management to mitigate the risk of irAE exacerbation. Most patients with mild (grade 1) irAEs may continue checkpoint inhibitor treatment with careful monitoring. For grade 2 irAEs, it is appropriate to suspend treatment, initiate corticosteroid therapy, and only resume treatment if the irAE resolves to < grade 1. Events classified as > grade 3 may require permanent treatment cessation and high-dose corticosteroid therapy. In clinical trials of PD-1/PD-L1 inhibitors across multiple cancer types, approximately 15% of patients with mUC developed irAEs requiring corticosteroid therapy. Training physicians and nurse providers and counseling patients regarding the early recognition of irAEs are mandatory to ensure timely irAE detection and optimized patient management. Hence, operationalizing an advanced bladder cancer clinic requires collaboration and coordination amongst urologists, medical and radiation oncologists, and other medical specialists who participate in the increasingly multimodal and multidisciplinary care of patients with bladder cancer.

中文翻译：

---

膀胱癌患者检查点抑制剂副作用的诊断和处理：泌尿科医师的观点

摘要

从2016年至今，我们目睹了针对PD-1 / PD-L1途径的免疫检查点抑制剂取得了飞速的进步，并获得了监管部门的批准，这大大改善了晚期和转移性尿路上皮癌（mUC）患者的生存率。尽管这些药物通常具有良好的耐受性，但它们独特的作用机制可能会增强细胞毒性T细胞介导的免疫，引起不同于常规化学疗法或分子靶向药物的独特副作用。最常见的免疫相关不良事件（irAEs）是皮炎，结肠炎，肺炎，甲状腺功能障碍和转氨酶，但是淋巴管系统渗透的任何器官系统都可能受到影响；另外，可能会发生神经病变和关节痛。任何级别的免疫介导事件都需要及时识别和适当管理，以减轻irAE加重的风险。大多数患有轻度（1级）irAE的患者可能会继续接受检查点抑制剂治疗并进行仔细监测。对于2级irAE，适当的是中止治疗，开始糖皮质激素治疗，并且只有在irAE降至<1级时才恢复治疗。分类为3级的事件可能需要永久性停药和大剂量糖皮质激素治疗。在跨多种癌症类型的PD-1 / PD-L1抑制剂的临床试验中，大约15％的mUC患者出现了需要皮质类固醇治疗的irAE。必须对医师和护士提供者进行培训，并就irAE的早期识别向患者提供咨询，以确保及时检测irAE和优化患者管理。