摘要:肾细胞癌 (renal cell carcinoma,RCC) 作为泌尿系统常见肿瘤之一,近年来免疫治疗方案的涌现极大改 善了转移性RCC患者的生存预后。但对于早期RCC,仍有较多患者出现术后肿瘤复发,故探索RCC围术期治疗 模式具有迫切的现实意义。目前,评估免疫治疗对围术期 RCC患者生存获益的临床研究陆续开展,这些临床研 究的开展将探索 RCC最佳围术期治疗方案和模式,有助于明确高复发风险患者,寻找 RCC围术期治疗的最佳获 益人群。这些前瞻性研究也将有望优化RCC患者的围术期治疗,为今后临床治疗提供重要依据。
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莫嘉志,鄢谢桥,盛锡楠.肾细胞癌围术期免疫治疗现况[J]. 泌尿外科杂志(电子版),2023,15(4):51-56. DOI:10.20020/j.CNKI.1674-7410.2023.04.10
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肾细胞癌 (renal cell carcinoma,RCC) 作为泌尿系统常见肿瘤之一,在全球最常见的肿瘤中排名第 16位,全球每年新发 RCC病例约43.1万例,死亡病例约17.9万例。对于适合手术治疗的患者,局限性RCC 的治疗标准是根治性肾切除术或部分肾切除术。但根据肿瘤大小、组织学和其他临床特征等危险因素,总体上仍有约20%的患者出现术后复发或远处转移。近年来,以拮抗程序性死亡蛋白-1 (programmed cell death protein 1,PD-1) 或程序性死亡蛋白配体-1 (programmed death-ligand1,PD-L1) 为代表的免疫检查点抑制剂的临床获批,代表RCC免疫治疗时代的来临。基于转移性RCC患者在免疫治疗中的获益,评估免疫治疗对围术期 RCC 患者的获益情况越来越受到全球学者的关注,RCC围术期治疗[辅助治疗和 (或) 新辅助治疗]被认为是临床需求但尚未得到满足的领域。
目前,已经有多种酪氨酸激酶抑制剂 (tyrosinekinase inhibitor,TKI) 和哺乳动物雷帕霉素靶蛋白抑制剂在 RCC 围术期治疗中进行尝试,但均未获得总生存期 (overall survival,OS) 获益。另一方面,采用帕博利珠单抗的免疫辅助治疗被证明可改善具有高复发风险的 RCC 患者术后的无病生存期 (disease-free survival,DFS),但 IMmotion 010、CheckMate 914、PROSPER 等研究均未得到接受RCC围术期免疫治疗后取得临床获益的结果。因此,本文将着重回顾目前 RCC 围术期免疫治疗的相关临床研究,探讨 RCC 围术期免疫治疗的最佳获益人群,并对免疫治疗的未来进行展望。
1 RCC 围术期免疫治疗相关临床研究
1.1 辅助治疗
1.2 新辅助治疗
1.3 新辅助治疗+辅助治疗
2 RCC 围术期免疫治疗的获益人群
3 结论
对 RCC 患者进行围术期免疫治疗其生存获益究竟如何,当前的临床研究没有提供全面且高级别的证据。尽管根据 KEYNOTE-564 临床研究的结果,抗 PD-1单药帕博利珠单抗已经获批用于美国和欧洲具有高复发风险的 RCC 患者的辅助治疗,但关于RCC的最佳围术期治疗方案和治疗模式仍有待探索,最可从RCC围术期治疗中获益的人群仍有待筛选和寻找。这些前瞻性的探究将有望优化 RCC 患者的围术期治疗,并成为今后指导临床治疗的重要依据。
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