Advances in bladder-preserving therapy for bladder cancer in the era of immunotherapy
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摘要: 膀胱癌是全球高发的恶性肿瘤之一，其中肌层浸润性膀胱癌(muscle invasive bladder cancer，MIBC)患者的预后较差。新辅助治疗后的根治性膀胱切除加盆腔淋巴结清扫术是MIBC的标准治疗方案。然而，根治术造成的身体创伤和围术期并发症使患者的生活质量严重受损。各种保膀胱治疗策略逐渐成为无法耐受手术或拒绝手术患者的有效替代方案。免疫治疗具有疗效持久和高耐受性的优点，极大地改变了膀胱癌的治疗现状。免疫治疗的应用可能会显著提升保膀胱治疗的成功率。本文就常规保膀胱治疗方案和基于免疫治疗联合保膀胱治疗策略相关进展进行综述。Abstract: Bladder cancer is one of the common malignant tumors worldwide, among which patients with muscle invasive bladder cancer(MIBC) have a poor prognosis. Radical cystectomy with pelvic lymph node dissection after neoadjuvant therapy is the standard treatment for MIBC. However, the physical trauma and perioperative complications caused by radical surgery have seriously impaired the quality of life of patients. Various bladder-preserving treatment strategies have emerged as effective alternatives for patients who cannot tolerate surgery or refuse surgery. Immunotherapy, with the advantages of long-lasting efficacy and high tolerability, has dramatically changed the treatment of bladder cancer. The application of immunotherapy may significantly improve the success rate of bladder-preserving treatment. This paper reviews the progress in conventional bladder-preserving treatment and immunotherapy-based combined bladder-preserving treatment strategies.
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表 1 靶向治疗药物在MIBC中的临床试验项目汇总表
临床试验编号 药物 MIBC疾病阶段 试验阶段 目的 开始时间 结束时间 纳入例数 NCT03390504 Erdafitinib vs
传统化疗或
Pembrolizumab局部晚期或转移 Ⅲ期 安全性 2018-03-23 2024-04-26 629 NCT03410693 Rogaratinib 局部晚期或转移 Ⅱ/Ⅲ期 安全性、耐受性 2018-05-31 2020-10-27 175 NCT04197986 Infigatinib ≥T2 Ⅲ期 有效性 2020-03-11 2023-01-11 39 NCT02401542 Vofatamab 局部晚期或转移 Ⅰ/Ⅱ期 安全性、有效性 2015-06-01 2019-11-01 71 
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表 2 免疫治疗为基础的新辅助治疗在MIBC中的临床试验项目汇总表
临床试验编号 药物 MIBC疾病阶段 试验阶段 目的 开始时间 结束时间 纳入例数 NCT02662309 Atezolizumab T2~T4a Ⅱ期 pCR 2016-02 2020-07 96 NCT02451423 Atezolizumab T2~T3 Ⅱ期 pCR，安全性 2016-03-29 2023-03-31 23 NCT02845323 Nivolumab+
UrelumabT2~T4，N0~
N2M0Ⅱ期 CD8+肿瘤反应 2017-05-16 2024-12 15 NCT02812420 Durvalumab+
tremelimumab≥T2 Ⅰ期 安全性和耐受性 2017-03-07 2023-03-31 54 NCT02736266 Pembrolizumab T2~T4aN0 Ⅱ期 pCR 2017-07-27 2022-09-23 174 NCT03387761 Nivolumab+
IpilimumabT3~4aN0M0；
T1~4aN1~3M0Ⅰb期 有效性 2018-01-15 2021-09-13 54 NCT03294304 Nivolumab+
GC≥T2 Ⅱ期 安全性和有效性 2018-01-29 2021-07-01 43 NCT02690558 Pembrolizumab/Placebo+GC T2~T4aN0M0 Ⅱ期 病理降期 2016-05 2026-01-30 39 NCT02365766 Pembrolizumab+GC；Pembrol-
izumab+CT2~4aN0M0 Ⅰb/
Ⅱ期安全性和有效性 2015-05-17 2023-05-31 83 NCT02256436 Pembrolizumabvs.传统化疗 局部晚期或转移 Ⅲ期 有效性 2014-10-22 2020-10-01 542 NCT03773666 Durvalumab+/-Oleclumab ≥T2 Ⅰ期 可行性 2019-02-20 2021-08-02 12 NCT03832673 Enfortumab+/Pembrolizumab ≥T2 Ⅱ期 安全性和有效性 2017-10-11 2026-12-31 348
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表 3 辅助免疫治疗在MIBC中的临床试验项目汇总表
临床试验编号 药物 MIBC疾病阶段 试验阶段 目的 开始时间 结束时间 纳入例数 NCT03244384 Pembrolizumab 局部晚期 Ⅲ期 DFS、OS 2017-09-21 2025-06-01 739 NCT02450331 Atezolizumab >T2 Ⅲ期 安全性和有效性 2015-10-05 2022-06-14 809 NCT02632409 Nivolumab >T2 Ⅲ期 安全性和有效性 2016-03-22 2027-05-15 709
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表 4 免疫治疗联合TMT/放化疗方案保膀胱治疗临床试验汇总表
临床试验编号 药物 治疗模式 试验阶段 观察指标 开始时间 结束时间 纳入例数 NCT03768570 Durvalumab TMT+Durvalumab Ⅱ期 有效性 2019-10-25 2026-03-31 82 NCT03171025 Nivolumab 放化疗+Nivolumab Ⅱ期 安全性和有效性 2017-07-10 2027-09 28 NCT02621151 Pembrolizumab Pembrolizumab+TMT Ⅱ期 安全性 2016-08-11 2025-12 60 NCT03747419 Avelumab Avelumab+放疗 Ⅱ期 安全性和有效性 2018-12-13 2031-01-31 24 NCT03775265 Atezolizumab 放化疗+Atezolizumab对比放化疗 Ⅲ期 有效性 2019-04-19 2027-06-01 475 NCT03617913 Avelumab Avelumab+放化疗 Ⅱ期 安全性和有效性 2018-09-19 2020-07-27 2 NCT02891161 Durvalumab Durvalumab+放疗+
DurvalumabⅡ期 有效性 2016-11 2022-03 26 NCT02662062 Pembrolizumab TMT+Pembrolizumab Ⅱ期 安全性和可行性 2016-08 2024-01 28 NCT05072600 Pembrolizumab TMT+Pembrolizumab Ⅱ期 有效性 2021-12-07 2029-11-01 54
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