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。
暂无相关信息！
[1] SUNG H, FERLAY J, SIEGEL RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries [J].CA Cancer J Clin, 2021, 71(3): 209-249.
[2] 向阳, 郭汝明, 李一竹, 等. 晚期肾癌患者精准免疫治疗的生 存分析[J]. 慢性病学杂志, 2022, 23(9): 1331-1334,1341.
[3] ESCUDIER B, PORTA C, SCHMIDINGER M, et al. Renal cell carcinoma: ESMO clinical practice guidelines for diagnosis, treatment and follow- up [J]. Ann Oncol, 2019, 30(5): 706-720.
[4] 王黛姣. 肾癌术后细胞因子治疗患者网络教育模式为基础的延续性护理干预效果[J]. 慢性病学杂志, 2020, 21(12): 1861-1863.
[5] MOTZER RJ, ESCUDIER B, MCDERMOTT DF, et al. Nivolumab versus everolimus in advanced renal- cell carcinoma [J]. N Engl J Med, 2015, 373(19): 1803-1813.
[6] MOTZER RJ, TANNIR NM, MCDERMOTT DF, et al. Nivolumab plus ipilimumab versus sunitinib in advanced renal- cell carcinoma [J]. N Engl J Med, 2018, 378(14): 1277-1290.
[7] 周莉, 盛锡楠. 晚期肾癌的免疫治疗进展与述评[J]. 肿瘤防治研 究, 2020, 47(3): 149-153.
[8] 夏琳, 宋媛媛, 郝瑞敏, 等. 晚期肾细胞癌治疗现状和新药研 发考虑[J]. 中国临床药理学杂志, 2020, 36(16): 2571-2577.
[9] HAAS NB, MANOLA J, UZZO RG, et al. Adjuvant sunitinib or sorafenib for high- risk, non- metastatic renalcell carcinoma (ECOG- ACRIN E2805): a double- blind, placebo- controlled, randomised, phase 3 trial [J]. Lancet, 2016, 387(10032): 2008-2016.
[10] MOTZER RJ, RAVAUD A, PATARD JJ, et al. Adjuvant sunitinib for high- risk renal cell carcinoma after nephrectomy: subgroup analyses and updated overall survival results [J]. Eur Urol, 2018, 73(1): 62-68.
[11] RYAN CW, TANGEN CM, HEATH EI, et al. EVEREST: everolim us for renal cancer ensuing surgical therapy- a phase Ⅲ study (SWOG S0931, NCT01120249) [J]. J Clin Oncol, 2022, 40(17): LBA4500.
[12] CHOUEIRI TK, TOMCZAK P, PARK SH, et al. Adjuvant pembrolizumab after nephrectomy in renal- cell carcinoma [J]. N Engl J Med, 2021, 385(8): 683-694.
[13] PAL SK, UZZO R, KARAM JA, et al. Adjuvant atezolizumab versus placebo for patients with renal cell carcinoma at increased risk of recurrence following resection (IMmotion010): a multicentre, randomised, double- blind, phase 3 trial [J]. Lancet, 2022, 400(10358):1103-1116.
[14] MOTZER RJ, RUSSO P, GRUNWALD V, et al. Adjuvant nivolumab plus ipilimumab versus placebo for localised renal cell carcinoma after nephrectomy (CheckMate 914): a double- blind, randomised, phase 3 trial [J]. Lancet, 2023, 401(10379): 821-832.
[15] ALLAF ME, KIM SE, MASTER VA, et al. PROSPER: Phase Ⅲ randomized study comparing PERioperative nivolumab versus observation in patients with renal cell carcinoma (RCC) undergoing nephrectomy (ECOG- ACRIN EA8143) [J]. J Clin Oncol, 2021, 39(15 suppl): TPS4596.
[16] POWLES T, TOMCZAK P, PARK SH, et al. Pembrolizumab versus placebo as post-nephrectomy adjuvant therapy for clear cell renal cell carcinoma (KEYNOTE- 564):30- month follow- up analysis of a multicentre, randomised, double- blind, placebocontrolled, phase 3 trial [J]. Lancet Oncol, 2022, 23(9): 1133-1144.
[17] OZA B, FRANGOU E, SMITH B, et al. RAMPART: a phase Ⅲ multi- arm multi- stage trial of adjuvant checkpoint inhibitors in patients with resected primary renal cell carcinoma (RCC) at high or intermediate risk of relapse [J]. Contemp Clin Trials, 2021, 108: 106482.
[18] CHOUEIRI TK, BEDKE J, KARAM JA, et al. Phase 3 LITESPARK- 022: pembrolizumab (pembro) plus hypoxiainducible factor 2α (HIF- 2α) inhibitor belzutifan as adjuvant treatment for clear cell renal cell carcinoma (ccRCC) [J]. J Clin Oncol, 2023, 41(6suppl): TPS748.
[19] ALBIGES L, TANNIR NM, BUROTTO M, et al. Firstline nivolumab plus ipilimumab versus sunitinib in patients without nephrectomy and with an evaluable primary renal tumor in the checkmate 214 trial [J]. Eur Urol, 2022, 81(3): 266-271.
[20] BEX A, ABU- GHANEM Y, VAN THIENEN JV, et al. Efficacy, safety, and biomarker analysis of neoadjuvant avelumab/axitinib in patients (pts) with localized renal cell carcinoma (RCC) who are at high risk of relapse after nephrectomy (NeoAvAx) [J]. J Clin Oncol, 2022, 40(6):289.
[21] KARAM JA, MSAOUEL P, MATIN SF, et al. A phase Ⅱ study of sitravatinib (Sitra) in combination with nivolumab (Nivo) in patients (Pts) undergoing nephrectomy for locally- advanced clear cell renal cell carcinoma (accRCC) [J]. J Clin Oncol, 2021, 39(6suppl): 312.
[22] CHOUEIRI TK, ETO M, MOTZER R, et al. Lenvatinib plus pembrolizumab versus sunitinib as first- line treatment of patients with advanced renal cell carcinoma (CLEAR): extended follow- up from the phase 3, randomised, openlabel study [J]. Lancet Oncol, 2023, 24(3): 228-238.
[23] KARAM JA, MSAOUEL P, HAYMAKER CL, et al. Phase Ⅱ trial of neoadjuvant sitravatinib plus nivolumab in patients undergoing nephrectomy for locally advanced clear cell renal cell carcinoma [J]. Nat Commun, 2023, 14(1):2684.
[24] HARSHMAN LC, PULIGANDLA M, HAAS NB, et al. PROSPER: a phase Ⅲ randomized study comparing perioperative nivolumab (nivo) versus observation in patients with localized renal cell carcinoma (RCC) undergoing nephrectomy (ECOG-ACRIN 8143) [J]. JClin Oncol, 2019, 37(7 suppl): TPS684.
[25] AU L, LITCHFIELD K, ROWAN A, et al. 907PDADAPTeR: a phase Ⅱ study of anti- PD1 (nivolumab) therapy as pre- and post- operative therapy in metastatic renal cell carcinoma [J]. Ann Oncol, 2019, 30: v359.
[26] ORNSTEIN MC, ZABELL J, WOOD LS, et al. A phase Ib trial of neoadjuvant/adjuvant durvalumab +/- tremelimumab in locally advanced renal cell carcinoma (RCC) [J]. J ClinOncol, 2020, 38(15 suppl): 5021.
[27] CORREA A, CONNOLLY DC, BALCIOGLU M, et al. Presence of circulating tumour DNA in surgically resected renal cell carcinoma is associated with advanced disease and poor patient prognosis [J]. Ann Oncol, 2019, 30: v32.
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
暂无相关信息！
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。
暂无相关信息！
暂无相关信息！