免疫检查点抑制剂毒性管理：膀胱毒性

免疫相关性膀胱毒性少见。

症状：

• 常见临床表现包括尿路刺激症状（尿急、尿频和尿痛）、血尿、排尿困难、夜尿增多、尿失禁等，部分可能伴随腹泻症状。
• 目前报道的大部分免疫相关性膀胱炎发生在用药3~7 周期后，也有用药长达77周期后发生免疫相关性膀胱炎［1-13］。
  

诊断：

• 目前尚无诊断免疫相关性膀胱炎的标准。出现泌尿系统症状时，完善尿常规、尿培养、尿液细胞学检查，排除感染和肿瘤后，需尽早考虑免疫相关性膀胱炎的可能，尽早给予激素治疗可能对控制病情进展和减少激素总用量有所帮助。
• 膀胱镜下活检可以辅助免疫相关性膀胱炎的诊断，免疫相关性膀胱炎膀胱镜下主要表现为膀胱黏膜糜烂和发红，病理结果显示尿路上皮细胞有淋巴细胞浸润，部分强表达PD-1或 PD-L1［1-4］。膀胱活检术中膀胱扩张可能对患者泌尿系统症状的缓解有一定积极作用［5］。
  

• 免疫检查点抑制剂毒性监测
  

治疗：

• 如果糖皮质激素疗效不佳，可考虑加用英夫利西单抗等免疫抑制剂治疗［6］。
  

G1：无症状或轻度症状，仅作临床或诊断观察

Ⅰ级推荐

• 继续ICIs
• 请泌尿外科会诊
  

G2：中度症状，影响工具性日常生活活动

Ⅰ级推荐

• 暂停ICIs
• 请泌尿外科会诊，考虑膀胱镜检查
• 排除感染和肿瘤所致膀胱炎后，考虑给予糖皮质激素治疗
  

Ⅱ级推荐

• 恢复至 G0~1后，根据发病的严重程度、前期对ICIs治疗的获益以及对糖皮质激素治疗的反应，谨慎选择患者恢复ICIs 治疗
  

G3：重度症状，需要静脉输注药物和住院

Ⅰ级推荐

• 永久停用ICIs
• 需要住院治疗或延长住院时间
• 请泌尿外科会诊，考虑膀胱镜检查
• 给予糖皮质激素治疗
• 若糖皮质激素治疗不敏感，可考虑加用英夫利西单抗等免疫抑制剂治疗
  

G4：危及生命

Ⅰ级推荐

• 永久停用ICIs
• 需要紧急治疗
• 请泌尿外科会诊，考虑膀胱镜检查
• 给予糖皮质激素治疗
• 若糖皮质激素治疗不敏感，可考虑加用英夫利西单抗等免疫抑制剂治疗
  

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参考指南：

中国临床肿瘤学会指南工作委员会.中国临床肿瘤学会 (CSCO) 免疫检查点抑制剂相关的毒性管理指南2023.人民卫生出版社.北京 2023

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参考文献

［1］ UEKI Y, MATSUKI M, KUBO T, et al.Non-bacterial cystitis withincreased expression of programmed death-ligand 1 inthe urothelium: Anunusual immune-related adverse event during treatment withpembrolizumab forlung adeno- carcinoma. IJU Case Rep,2020, 3 (6): 266-269.

［2］ SCHNEIDER S, ALEZRA E, YACOUB M, etal. Aseptic cystitisinduced by nivolumaband ipilimumab combination for metastatic melanoma. Melanoma Res, 2021,31 (5): 487-489.

［3］ OBAYASHI A, HAMADA-NISHIMOTOM,FUJIMOTO Y, et al. Non-bacterial cystitis with increased expression ofprogrammed cell death ligand 1 in theurothelium: An unusual immune-relatedadverse event after atezolizumab administration for metastatic breastcancer.Cureus, 2022, 14 (5): e25486.

［4］ WANG Z, ZHU L, HUANG Y, et al.Successful treatmentof immune-related cystitisby Chai-Ling-Tang (Sairei-To) ina gastric carcinomapatient: Case report and literature review. Explore (NY),2022, 4: S1550-8307(22) 00042-8.

［5］ YAJIMA S, NAKANISHI Y, MATSUMOTO S,etal. Improvement of urinary symptoms after bladder biopsy: A case ofpathologically proven allergy-relatedcystitis during administration ofnivolumab. IJU Case Rep, 2021, 4 (4): 213- 215.

［6］ FUKUNAGA H, SUMII K, KAWAMURA S, etal. A case ofsteroid-resistant cystitis as an immune-related adverse eventduring treatmentwith nivolumab for lung cancer,which was successfully treatedwith infliximab. IJU Case Rep, 2022,5 (6): 521-523.

［7］ OZAKI K, TAKAHASHI H,MURAKAMI Y, etal. A case of cystitis after administration of nivolumab. IntCancer Conf J,2017, 6 (4): 164-166.

［8］ SHIMATANI K, YOSHIMOTOT, DOI Y, etal. Two cases of nonbacterial cystitis associated with nivolumab,theantiprogrammed-death-receptor-1inhibitor. Urol Case Rep, 2018, 17: 97-99.

［9］HUSSEINIAK E, LAFOESTEA H, MANSUET-LUPO A, et al. A case of severe interstitialcystitisassociated with pembrolizumab. CurrProb Cancer, 2021, 4: 100101.

［10］ ZHUS, BIAN L, LV J, et al. A casereport of non-bacterial cystitiscaused by immune checkpoint inhibitors.FrontImmunol, 2021, 12: 788629.

［11］ ZHU L, WANG Z, STEBBING J, et al.Immunotherapy-related cystitis:Case report and review of the literature.

Onco TargetsTher, 2021, 14: 4321-4328.

［12］TU L, YE Y, TANG X, et al.Case report: A case of sintilimabinducedcystitis/ureteritis and review ofsintilimab- related adverse events.FrontOncol, 2021, 11: 757069.

［13］ HE X,TU R, ZENG S, et al.Non-bacterial cystitis secondary to pembrolizumab: A casereport and review ofthe literature.Curr Probl Cancer, 2022, 46 (4): 100863.

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