摘要:尿路上皮癌 (urothelial carcinoma,UC) 是泌尿系最常见的恶性肿瘤之一,具有发病率高、发生隐匿、 多点原发、易复发等特点。目前,指南推荐新辅助化疗 (neoadjuvant chemotherapy, NAC) 联合根治性膀胱 切 除 术 (radical cystectomy,RC) 或肾输尿管切除术为肌层浸润性尿路上皮癌(muscle- invasive urothelial carcinoma,MIUC) 标准的治疗方法。同时,以顺铂为基础的联合化疗作为一线治疗用于不可切除和转移性的晚 期 UC患者,但受各种因素影响,并非所有 UC患者均可从中获益。近年来,有大量实验研究关于程序性细胞死 亡蛋白-1(programmed cell death protein 1,PD-1)/程序性细胞死亡配体-1(programmed cell death ligand 1, PD-L1) 抑制剂的疗效和安全性,PD-1/PD-L1抑制剂也逐渐被批准用于 UC 的一、二线治疗。本文对 PD-1/ PD-L1抑制剂在UC治疗中的应用进展作一综述,以期为癌症患者的临床治疗提供帮助。
表 1 已获 FDA 批准用于治疗转移性尿路上皮癌的 PD-1/PD-L1 抑制剂
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李银,王自勇,毕颖,等.PD-1/PD-L1 抑制剂在尿路上皮癌治疗中的应用进展[J]. 泌尿外科杂志(电子版),2023,15(4):57-61. DOI:10.20020/j.CNKI.1674-7410.2023.04.11
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尿路上皮癌 (urothelial carcinoma,UC) 是泌尿系最常见的恶性肿瘤之一,包括位于下尿路的膀胱和尿道恶性肿瘤及位于上尿路的肾盂和输尿管恶性肿瘤,其中约90%为膀胱UC[1]。2022年美国新发UC病例约 160 180例,新发死亡病例约 31 020例,其中膀胱癌病例高达 81 180例,死亡病例为 17 100例[2]。对于肌层浸润性尿路上皮癌 (muscle-invasiveurothelial carcinoma,MIUC),标准的治疗方法包括根治性膀胱切除术 (radical cystectomy,RC) 或肾输尿管切 除术联合新辅助化疗 (neoadjuvant chemotherapy,NAC)。同时对于不可切除或转移性UC, 以顺铂为基 础的联合化疗是其标准治疗方式[3-4]。但并非所有MIUC患者都能从中获益,大多数晚期患者在治疗后仍会继续进展,很少有患者在诊断后存活5年以上。同时,无进展生存期 (progressionfree survival,PFS) 和总生存期 (overall survival,OS) 也会受到化疗耐药性的限制[5-6]。
近年来,免疫治疗的不断发展给晚期UC的治疗带来了希望 , 其中免疫检查点抑制剂(immunecheckpoint inhibitors,ICI) 逐渐成为代表性的治疗方法[7]。有研究发现,具有基因组不稳定、程序性细胞死亡配体-1 (programmed cell death ligand 1,PD-L1) 高表达、DNA 损伤反应突变和高肿瘤突变负担等特点的UC对ICI的治疗具有更好的治疗反应[6]。现有5种程序性细胞死亡蛋白-1 (programmed celldeath protein 1,PD- 1) /PD-L1 抑制剂被广泛应用[8]。 本文对已获美国食品和药物管理局 (Foodand Drug Administration,FDA) 批准使用的 5 种PD-1/PD-L1抑制剂在作用机制、获批依据、联合应用等方面的应用进展进行综述。
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ICI治疗已广泛用于治疗晚期UC,因免疫机制的复杂性,单一治疗很难达到预期效果。随着肿瘤免疫治疗研究的不断深入,将会有越来越多优化治疗方案被制定,且随着对基因组学及相关免疫机制的进一步研究和免疫检测技术的进步,采用多种ICI联合治疗的方法是一种新的发展趋势。同时,建立临床预测模型、寻找更准确地预测生物标志物可以更加全面地预测ICI疗效。
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