APP
产业链接
公众号矩阵
动脉智库
活动会议
解决方案
动脉AI
搜索
EN
登录
首页
情报
原创
专题
报告
链接
直播
活动

动脉网APP
扫码下载

新辅助吉西他滨-顺铂加替西珠单抗治疗可切除的肌肉浸润性膀胱癌症患者：一项多中心、单臂、2期试验

Neoadjuvant gemcitabine–cisplatin plus tislelizumab in persons with resectable muscle-invasive bladder cancer: a multicenter, single-arm, phase 2 trial

Nature 等信源发布 2024-09-10 19:15

可切换为仅中文

AbstractProgrammed death 1 blockade (tislelizumab) has been approved for metastatic urothelial carcinoma but not as part of neoadjuvant therapy for muscle-invasive bladder cancer (MIBC). In this multicenter single-arm trial (ChiCTR2000037670), 65 participants with cT2-4aN0M0 MIBC received neoadjuvant gemcitabine–cisplatin plus tislelizumab; 57 of them underwent radical cystectomy (RC).

摘要程序性死亡1阻断剂（tislelizumab）已被批准用于转移性尿路上皮癌，但不是肌肉浸润性膀胱癌（MIBC）新辅助治疗的一部分。在这项多中心单臂试验（ChiCTR2000037670）中，65名cT2-4aN0M0 MIBC参与者接受了新辅助吉西他滨-顺铂联合tislelizumab；其中57例行根治性膀胱切除术（RC）。

The primary endpoint of pathologic complete response (pCR) rate was 50.9% (29/57, 95% confidence interval (CI) 37.3–64.4%) and the pathologic downstaging (secondary endpoint) rate was 75.4% (43/57, 95% CI 62.2–85.9%) in participants undergoing RC. Genomic and transcriptomic analyses revealed three MIBC molecular subtypes (S): S1 (immune-desert) with activated cell-cycle pathway, S2 (immune-excluded) with activated transforming growth factor-β pathway and S3 (immune-inflamed) with upregulated interferon-α and interferon-γ response.

在接受RC的参与者中，病理完全缓解（pCR）率的主要终点为50.9%（29/57，95%置信区间（CI）37.3-64.4%），病理降级（次要终点）率为75.4%（43/57，95%CI 62.2-85.9%）。基因组学和转录组学分析揭示了三种MIBC分子亚型：具有激活的细胞周期途径的S1（免疫沙漠），具有激活的转化生长因子-β途径的S2（免疫排除）和具有上调的干扰素-α和干扰素-γ应答的S3（免疫发炎）。

Post hoc analysis showed pCR rates of 16% (3/19, S1), 77% (10/13, S2) and 80% (12/15, S3) (P = 0.006). In conclusion, neoadjuvant gemcitabine–cisplatin plus tislelizumab for MIBC was compatible with an enhanced pCR rate..

事后分析显示pCR率为16%（3/19，S1），77%（10/13，S2）和80%（12/15，S3）（P=0.006）。总之，新辅助吉西他滨-顺铂联合tislelizumab治疗MIBC可提高pCR率。。

Access through your institution

通过您的机构访问

Buy or subscribe

购买或订阅

This is a preview of subscription content, access via your institution

这是订阅内容的预览，可通过您的机构访问

Access options

访问选项

Access through your institution

通过您的机构访问

Access through your institution

通过您的机构访问

Change institution

变革机构

Buy or subscribe

购买或订阅

Access Nature and 54 other Nature Portfolio journalsGet Nature+, our best-value online-access subscription24,99 € / 30 dayscancel any timeLearn moreSubscribe to this journalReceive 12 digital issues and online access to articles111,21 € per yearonly 9,27 € per issueLearn moreBuy this articlePurchase on SpringerLinkInstant access to full article PDFBuy nowPrices may be subject to local taxes which are calculated during checkout.

Access Nature和54本其他Nature Portfolio journalsGet Nature+，我们最有价值的在线订阅24,99欧元/30天浏览所有时间更多订阅本期刊每年收到12期数字期刊和在线访问文章111,21欧元每期仅9,27欧元更多了解更多购买本文在SpringerLink上购买即时访问完整文章PDFBuy Now价格可能需要缴纳结帐期间计算的当地税费。

Additional access options:

其他访问选项：

Log in

登录

Learn about institutional subscriptions

了解机构订阅

Read our FAQs

阅读我们的常见问题

Contact customer support

联系客户支持

Fig. 1: Kaplan–Meier curves of EFS, OS and RFS.Fig. 2: Somatic mutations and copy number variations in pretreatment tumors from participants with pCR versus non-pCR.Fig. 3: Molecular characteristics and immune profiles in pretreatment tumors from participants with pCR versus non-pCR.Fig. 4: MIBC subtypes in pretreatment tumors.Fig.

图1:EFS，OS和RFS的Kaplan-Meier曲线。图2:pCR与非pCR参与者治疗前肿瘤的体细胞突变和拷贝数变异。图3:pCR与非pCR参与者的预处理肿瘤的分子特征和免疫谱。图4：治疗前肿瘤中的MIBC亚型。。

5: Comparison of paired pretreatment and posttreatment tumors.Fig. 6: Summarized characteristics of three MIBC subtypes..

5： 配对治疗前和治疗后肿瘤的比较。图6：三种MIBC亚型的总结特征。。

Data availability

数据可用性

RNA and DNA sequencing data that support the findings of this study were deposited to the Genome Sequence Archive in National Genomics Data Center, China National Center for Bioinformation and Beijing Institute of Genomics, Chinese Academy of Sciences under accession code HRA006086. The dataset derived from this resource that supports the findings of this study is available at https://bigd.big.ac.cn/gsa-human/browse/HRA006086.

支持本研究结果的RNA和DNA测序数据已保存在国家基因组学数据中心，中国国家生物信息中心和中国科学院北京基因组研究所的基因组序列档案中，登录号为HRA006086。从该资源中获得的支持本研究结果的数据集可在https://bigd.big.ac.cn/gsa-human/browse/HRA006086.

RNA and DNA sequencing data generated for this study are subjected to the regulations by the Ministry of Science and Technology of the People’s Republic of China. The hg19 human genome can be found at https://www.ncbi.nlm.nih.gov/datasets/genome/GCF_000001405.13/. All other data supporting the findings of this study are available from T.L.

本研究产生的RNA和DNA测序数据符合中华人民共和国科学技术部的规定。hg19人类基因组可以在https://www.ncbi.nlm.nih.gov/datasets/genome/GCF_000001405.13/.。

(lintx@mail.sysu.edu.cn) or K.L. (likw6@mail.sysu.edu.cn) on reasonable request. Individual deidentified participant data (including data dictionaries, text and tables) that underlie the results reported in this article will be eligible for data sharing requests after January 1, 2027. The study protocol can be found in the Supplementary Information.

（笑声）(lintx@mail.sysu.edu.cn)或K.L(likw6@mail.sysu.edu.cn)应合理要求。作为本文报告结果基础的个人身份不明的参与者数据（包括数据字典，文本和表格）将在2027年1月1日后有资格获得数据共享请求。研究方案可以在补充信息中找到。

Researchers should send methodologically sound proposals directly to T.L. (lintx@mail.sysu.edu.cn) or K.L. (likw6@mail.sysu.edu.cn) for data requests. The reuse of the individual participant data is permitted only for revalidation of the results or for meta-analysis. Source data are provided with this paper..

研究人员应该直接向T.L.发送方法上合理的建议(lintx@mail.sysu.edu.cn)或K.L(likw6@mail.sysu.edu.cn)用于数据请求。仅允许重复使用单个参与者数据以重新验证结果或进行荟萃分析。本文提供了源数据。。

Code availability

代码可用性

All relevant package and software information is provided in the Methods. No custom code was generated in the course of this study.

方法中提供了所有相关的软件包和软件信息。在这项研究过程中没有生成自定义代码。

ReferencesKamat, A. M. et al. Bladder cancer. Lancet 388, 2796–2810 (2016).Article

参考文献Kamat，A.M。等人，膀胱癌。柳叶刀3882796-2810（2016）。文章

PubMed

PubMed

Google Scholar

谷歌学者

Alfred Witjes, J. et al. European association of urology guidelines on muscle-invasive and metastatic bladder cancer: summary of the 2023 guidelines. Eur. Urol. 85, 17–31 (2024).Article

Alfred Witjes，J.等。欧洲泌尿外科协会肌肉浸润性和转移性膀胱癌指南：2023年指南摘要。欧元Urol。85，17-31（2024）。文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Flaig, T. W. et al. A randomized phase II study of coexpression extrapolation (COXEN) with neoadjuvant chemotherapy for bladder cancer (SWOG S1314; NCT02177695). Clin. Cancer Res. 27, 2435–2441 (2021).Article

Flaig，T.W.等人，《共表达外推（COXEN）与膀胱癌新辅助化疗的随机II期研究》（SWOG S1314；NCT02177695）。临床。癌症研究272435-2441（2021）。文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Zargar, H. et al. Multicenter assessment of neoadjuvant chemotherapy for muscle-invasive bladder cancer. Eur. Urol. 67, 241–249 (2015).Article

Zargar，H。等。肌肉浸润性膀胱癌新辅助化疗的多中心评估。欧元Urol。67241-249（2015）。文章

PubMed

PubMed

Google Scholar

谷歌学者

Iyer, G. et al. Neoadjuvant gemcitabine–cisplatin plus radical cystectomy–pelvic lymph node dissection for muscle-invasive bladder cancer: a 12-year experience. Clin. Genitourin. Cancer 18, 387–394 (2020).Article

新辅助吉西他滨-顺铂联合根治性膀胱切除术-盆腔淋巴结清扫术治疗肌肉浸润性膀胱癌：12年经验。临床。泌尿生殖系统癌症18387-394（2020）。文章

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Powles, T. et al. Clinical efficacy and biomarker analysis of neoadjuvant atezolizumab in operable urothelial carcinoma in the ABACUS trial. Nat. Med. 25, 1706–1714 (2019).Article

在ABACUS试验中，新辅助阿唑珠单抗在可手术尿路上皮癌中的临床疗效和生物标志物分析。《自然医学杂志》251706-1714（2019）。文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Necchi, A. et al. Pembrolizumab as neoadjuvant therapy before radical cystectomy in patients with muscle-invasive urothelial bladder carcinoma (PURE-01): an open-label, single-arm, phase II study. J. Clin. Oncol. 36, 3353–3360 (2018).Article

Necchi，A。等人。Pembrolizumab作为肌肉浸润性尿路上皮膀胱癌患者根治性膀胱切除术前的新辅助治疗（PURE-01）：一项开放标签，单臂，II期研究。J、 临床。。363353-3360（2018）。文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

de Biasi, A. R., Villena-Vargas, J. & Adusumilli, P. S. Cisplatin-induced antitumor immunomodulation: a review of preclinical and clinical evidence. Clin. Cancer Res. 20, 5384–5391 (2014).Article

de Biasi，A.R.，Villena-Vargas，J。＆Adusumilli，P.S。顺铂诱导的抗肿瘤免疫调节：临床前和临床证据的综述。临床。癌症研究205384-5391（2014）。文章

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Rose, T. L. et al. Phase II study of gemcitabine and split-dose cisplatin plus pembrolizumab as neoadjuvant therapy before radical cystectomy in patients with muscle-invasive bladder cancer. J. Clin. Oncol. 39, 3140–3148 (2021).Article

Rose，T.L.等。吉西他滨和分剂量顺铂联合派姆单抗作为肌肉浸润性膀胱癌患者根治性膀胱切除术前新辅助治疗的II期研究。J、 临床。。393140-3148（2021）。文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Funt, S. A. et al. Neoadjuvant atezolizumab with gemcitabine and cisplatin in patients with muscle-invasive bladder cancer: a multicenter, single-arm, phase II trial. J. Clin. Oncol. 40, 1312–1322 (2022).Article

Funt，S.A.等。新辅助阿唑珠单抗联合吉西他滨和顺铂治疗肌肉浸润性膀胱癌：一项多中心单臂II期临床试验。J、 临床。。401312-1322（2022）。文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Zhang, T. et al. The binding of an anti-PD-1 antibody to FcγRΙ has a profound impact on its biological functions. Cancer Immunol. Immunother. 67, 1079–1090 (2018).Article

Zhang，T。等人。抗PD-1抗体与FcγR i的结合对其生物学功能产生了深远的影响。。免疫疗法。671079-1090（2018）。文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Ye, D. et al. Tislelizumab in Asian patients with previously treated locally advanced or metastatic urothelial carcinoma. Cancer Sci. 112, 305–313 (2021).Article

Ye，D.等人，Tislelizumab治疗亚洲先前接受过局部晚期或转移性尿路上皮癌治疗的患者。癌症科学。112305-313（2021）。文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Robertson, A. G. et al. Comprehensive molecular characterization of muscle-Invasive bladder cancer. Cell 171, 540–556 (2017).Article

Robertson，A.G.等人，《肌肉浸润性膀胱癌的综合分子表征》。细胞171540-556（2017）。文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Plimack, E. R. et al. Defects in DNA repair genes predict response to neoadjuvant cisplatin-based chemotherapy in muscle-invasive bladder cancer. Eur. Urol. 68, 959–967 (2015).Article

Plimack，E.R。等。DNA修复基因缺陷预测肌肉浸润性膀胱癌对新辅助顺铂化疗的反应。欧元Urol。68959-967（2015）。文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Van Allen, E. M. et al. Somatic ERCC2 mutations correlate with cisplatin sensitivity in muscle-invasive urothelial carcinoma. Cancer Discov. 4, 1140–1153 (2014).Article

Van Allen，E.M.等人。体细胞ERCC2突变与肌肉浸润性尿路上皮癌中顺铂敏感性相关。癌症发现。41140-1153（2014）。文章

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Adib, E. et al. CDKN2A alterations and response to immunotherapy in solid tumors. Clin. Cancer Res. 27, 4025–4035 (2021).Article

。临床。癌症研究274025-4035（2021）。文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Huang, Q. et al. Loss of TSC1/TSC2 sensitizes immune checkpoint blockade in non-small cell lung cancer. Sci. Adv. 8, eabi9533 (2022).Article

Huang，Q。等人。TSC1/TSC2的缺失使非小细胞肺癌的免疫检查点阻断敏感。科学。Adv.8，eabi9533（2022）。文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Lu, Q. et al. Rheb1 protects against cisplatin-induced tubular cell death and acute kidney injury via maintaining mitochondrial homeostasis. Cell Death Dis. 11, 364 (2020).Article

Lu，Q。等人。Rheb1通过维持线粒体稳态来防止顺铂诱导的肾小管细胞死亡和急性肾损伤。。11364（2020）。文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Teo, M. Y. et al. Alterations in DNA damage response and repair genes as potential marker of clinical benefit from PD-1/PD-L1 blockade in advanced urothelial cancers. J. Clin. Oncol. 36, 1685–1694 (2018).Article

Teo，M.Y.等人。DNA损伤反应和修复基因的改变作为晚期尿路上皮癌中PD-1/PD-L1阻断的临床益处的潜在标志物。J、 临床。。361685-1694（2018）。文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Teo, M. Y. et al. DNA damage response and repair gene alterations are associated with improved survival in patients with platinum-treated advanced urothelial carcinoma. Clin. Cancer Res. 23, 3610–3618 (2017).Article

DNA损伤反应和修复基因改变与铂类治疗的晚期尿路上皮癌患者的生存率提高有关。临床。癌症研究233610-3618（2017）。文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

de Visser, K. E. & Joyce, J. A. The evolving tumor microenvironment: from cancer initiation to metastatic outgrowth. Cancer Cell 41, 374–403 (2023).Article

de Visser，K.E。和Joyce，J.A。不断发展的肿瘤微环境：从癌症起始到转移性生长。癌细胞41374-403（2023）。文章

PubMed

PubMed

Google Scholar

谷歌学者

Tian, B. et al. Curcumin inhibits urothelial tumor development by suppressing IGF2 and IGF2-mediated PI3K/AKT/mTOR signaling pathway. J. Drug Target. 25, 626–636 (2017).Article

Tian，B。等人。姜黄素通过抑制IGF2和IGF2介导的PI3K/AKT/mTOR信号通路来抑制尿路上皮肿瘤的发展。J、 药物目标。25626-636（2017）。文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Das, R. et al. An integrated functional and clinical genomics approach reveals genes driving aggressive metastatic prostate cancer. Nat. Commun. 12, 4601 (2021).Article

Das，R。等人。综合功能和临床基因组学方法揭示了驱动侵袭性转移性前列腺癌的基因。国家公社。124601（2021）。文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

De Vitis, C. et al. ALDOC- and ENO2-driven glucose metabolism sustains 3D tumor spheroids growth regardless of nutrient environmental conditions: a multi-omics analysis. J. Exp. Clin. Canc. Res. 42, 69 (2023).Article

De Vitis，C。等人。ALDOC和ENO2驱动的葡萄糖代谢维持3D肿瘤球体的生长，无论营养环境条件如何：多组学分析。J、 实验临床。坎克。第42、69（2023）号决议。文章

Google Scholar

谷歌学者

Januchowski, R. et al. Drug transporter expression profiling in chemoresistant variants of the A2780 ovarian cancer cell line. Biomed. Pharmacother. 68, 447–453 (2014).Article

Januchowski，R。等人。A2780卵巢癌细胞系化学抗性变体中的药物转运蛋白表达谱。生物医学。药剂师。68447-453（2014）。文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Maddika, S. et al. Cell survival, cell death and cell cycle pathways are interconnected: implications for cancer therapy. Drug Resist. Updat. 10, 13–29 (2007).Article

Maddika，S。等人。细胞存活，细胞死亡和细胞周期途径是相互关联的：对癌症治疗的影响。抗药性。。10,13-29（2007）。文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Rooney, M. S., Shukla, S. A., Wu, C. J., Getz, G. & Hacohen, N. Molecular and genetic properties of tumors associated with local immune cytolytic activity. Cell 160, 48–61 (2015).Article

Rooney，M.S.，Shukla，S.A.，Wu，C.J.，Getz，G。＆Hacohen，N。与局部免疫溶细胞活性相关的肿瘤的分子和遗传特性。细胞160,48-61（2015）。文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Kamoun, A. et al. A consensus molecular classification of muscle-invasive bladder cancer. Eur. Urol. 77, 420–433 (2020).Article

Kamoun，A.等人，《肌肉浸润性膀胱癌的共识分子分类》。欧元Urol。77420-433（2020）。文章

PubMed

PubMed

Google Scholar

谷歌学者

Mariathasan, S. et al. TGFβ attenuates tumour response to PD-L1 blockade by contributing to exclusion of T cells. Nature 554, 544–548 (2018).Article

Mariathasan，S。等人。TGFβ通过有助于排除T细胞来减弱肿瘤对PD-L1阻断的反应。自然554544-548（2018）。文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Liu, Z. et al. TTN/OBSCN ‘double‐hit’ predicts favourable prognosis, ‘immune‐hot’ subtype and potentially better immunotherapeutic efficacy in colorectal cancer. J. Cell. Mol. Med. 25, 3239–3251 (2021).Article

Liu，Z。等人。TTN/OBSCN“双击”预测结直肠癌的预后良好，“免疫热”亚型和潜在更好的免疫治疗效果。J、 细胞。摩尔医学253239-3251（2021）。文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Zhang, L., Han, X. & Shi, Y. Association of MUC16 mutation with response to immune checkpoint inhibitors in solid tumors. JAMA Netw. Open 3, e2013201 (2020).Article

Zhang，L.，Han，X。＆Shi，Y。MUC16突变与实体瘤中免疫检查点抑制剂反应的关联。JAMA网络。开放3，e2013201（2020）。文章

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Subramanian, A. et al. A next generation connectivity map: L1000 platform and the first 1,000,000 profiles. Cell 171, 1437–1452 (2017).Article

Subramanian，A.等人，《下一代连接图：L1000平台和前1000000个配置文件》。细胞1711437-1452（2017）。文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Carneiro, B. A. et al. Phase I study of elraglusib (9-ING-41), a glycogen synthase kinase-3β inhibitor, as monotherapy or combined with chemotherapy in patients with advanced malignancies. Clin. Cancer Res. 30, 522–531 (2024).Article

。临床。癌症研究30522-531（2024）。文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Song, Y. et al. Fibroblast growth factor receptor 3 mutation attenuates response to immune checkpoint blockade in metastatic urothelial carcinoma by driving immunosuppressive microenvironment. J. Immunother. Cancer 11, e006643 (2023).Article

Song，Y。等人。成纤维细胞生长因子受体3突变通过驱动免疫抑制微环境来减弱转移性尿路上皮癌对免疫检查点阻断的反应。J、 免疫疗法。癌症11，e006643（2023）。文章

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Cathomas, R. et al. Perioperative chemoimmunotherapy with durvalumab for muscle-invasive urothelial carcinoma: primary analysis of the single-arm phase II trial SAKK 06/17. J. Clin. Oncol. 41, 5131–5139 (2023).Article

Cathomas，R.等。durvalumab治疗肌肉浸润性尿路上皮癌的围手术期化学免疫治疗：单臂II期试验SAKK 06/17的初步分析。J、 临床。。415131-5139（2023）。文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Brown, J. et al. HCRN GU14-188: phase Ib/II study of neoadjuvant pembrolizumab and chemotherapy for T2-4aN0M0 urothelial cancer. J. Clin. Oncol. 41, 448–448 (2023).Article

Brown，J.等人，HCRN GU14-188：新辅助pembrolizumab和T2-4aN0M0尿路上皮癌化疗的Ib/II期研究。J、 临床。。41448-448（2023）。文章

Google Scholar

谷歌学者

Gupta, S. et al. Results from BLASST-1 (Bladder Cancer Signal Seeking Trial) of nivolumab, gemcitabine, and cisplatin in muscle invasive bladder cancer (MIBC) undergoing cystectomy. J. Clin. Oncol. 38, 439–439 (2020).Article

Gupta，S.等人对接受膀胱切除术的肌肉浸润性膀胱癌（MIBC）进行nivolumab，吉西他滨和顺铂的BLAST-1（膀胱癌信号寻求试验）的结果。J、 临床。。38439-439（2020）。文章

Google Scholar

谷歌学者

Powles, T. et al. Pembrolizumab alone or combined with chemotherapy versus chemotherapy as first-line therapy for advanced urothelial carcinoma (KEYNOTE-361): a randomised, open-label, phase 3 trial. Lancet Oncol. 22, 931–945 (2021).Article

Powles，T。等人。Pembrolizumab单独或联合化疗与化疗作为晚期尿路上皮癌的一线治疗（KEYNOTE-361）：一项随机，开放标签的3期临床试验。柳叶刀Oncol。22931-945（2021）。文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Bamias, A. et al. Atezolizumab monotherapy versus chemotherapy in untreated locally advanced or metastatic urothelial carcinoma (IMvigor130): final overall survival analysis from a randomised, controlled, phase 3 study. Lancet Oncol. 25, 46–61 (2024).Article

Bamias，A。等人。未经治疗的局部晚期或转移性尿路上皮癌（IMvigor130）中的Atezolizumab单药治疗与化疗：来自随机对照3期研究的最终总生存分析。柳叶刀Oncol。25，46-61（2024）。文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Van Der Heijden, M. S. et al. Nivolumab plus gemcitabine–cisplatin in advanced urothelial carcinoma. N. Engl. J. Med. 389, 1778–1789 (2023).Article

Van Der Heijden，M.S.等人。Nivolumab联合吉西他滨-顺铂治疗晚期尿路上皮癌。N、 英语。J、 医学3891778-1789（2023）。文章

PubMed

PubMed

Google Scholar

谷歌学者

Bajorin, D. F. et al. Adjuvant nivolumab versus placebo in muscle-invasive urothelial carcinoma. N. Engl. J. Med. 384, 2102–2114 (2021).Article

Bajorin，D.F。等人。肌肉浸润性尿路上皮癌中辅助nivolumab与安慰剂的比较。N、 英语。J、 医学3842102-2114（2021）。文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Szabados, B. et al. Final results of neoadjuvant atezolizumab in cisplatin-ineligible patients with muscle-invasive urothelial cancer of the bladder. Eur. Urol. 82, 212–222 (2022).Article

Szabados，B。等人。新辅助阿唑珠单抗治疗不符合顺铂条件的膀胱肌层浸润性尿路上皮癌患者的最终结果。欧元Urol。82212-222（2022）。文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Galsky, M. D. et al. Determinants of survival with combined HER2 and PD-1 blockade in metastatic esophagogastric cancer. Clin. Cancer Res. 29, 3633–3640 (2023).Article

。临床。癌症研究293633-3640（2023）。文章

Google Scholar

谷歌学者

Kitamura, H. et al. Randomised phase III study of neoadjuvant chemotherapy with methotrexate, doxorubicin, vinblastine and cisplatin followed by radical cystectomy compared with radical cystectomy alone for muscle-invasive bladder cancer: Japan Clinical Oncology Group Study JCOG0209.

Kitamura，H.等人，《甲氨蝶呤、多柔比星、长春碱和顺铂新辅助化疗联合根治性膀胱切除术与单纯根治性膀胱切除术治疗肌层浸润性膀胱癌的随机III期研究：日本临床肿瘤组研究JCOG0209》。

Ann. Oncol. 25, 1192–1198 (2014).Article .

安科。251192-1198（2014）。文章。

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Grossman, H. B. et al. Neoadjuvant chemotherapy plus cystectomy compared with cystectomy alone for locally advanced bladder cancer. N. Engl. J. Med. 349, 859–866 (2003).Article

Grossman，H.B.等。新辅助化疗加膀胱切除术与单纯膀胱切除术治疗局部晚期膀胱癌的比较。N、 英语。J、 医学杂志349859-866（2003）。文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Strandgaard, T. et al. Field cancerization is associated with tumor development, T-cell exhaustion, and clinical outcomes in bladder cancer. Eur. Urol. 85, 82–92 (2024).Article

Strandgaard，T。等人。野外癌变与膀胱癌的肿瘤发展，T细胞衰竭和临床结果有关。欧元Urol。85，82-92（2024）。文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Robertson, A. G. et al. Expression-based subtypes define pathologic response to neoadjuvant immune-checkpoint inhibitors in muscle-invasive bladder cancer. Nat. Commun. 14, 2126 (2023).Article

基于表达的亚型定义了肌肉浸润性膀胱癌对新辅助免疫检查点抑制剂的病理反应。国家公社。142126（2023）。文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Kortlever, R. M. et al. Myc cooperates with Ras by programming inflammation and immune suppression. Cell 171, 1301–1315 (2017).Article

Kortlever，R.M。等人Myc通过编程炎症和免疫抑制与Ras合作。细胞1711301-1315（2017）。文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Fang, X. et al. Sintilimab plus bevacizumab, oxaliplatin and capecitabine as first-line therapy in RAS-mutant, microsatellite stable, unresectable metastatic colorectal cancer: an open-label, single-arm, phase II trial. EClinicalMedicine 62, 102123 (2023).Article

Fang，X。等人。辛迪单抗联合贝伐单抗，奥沙利铂和卡培他滨作为RAS突变，微卫星稳定，不可切除的转移性结直肠癌的一线治疗：一项开放标签，单臂，II期试验。EClinicalMedicine 62102123（2023）。文章

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Kent, L. N. & Leone, G. The broken cycle: E2F dysfunction in cancer. Nat. Rev. Cancer 19, 326–338 (2019).Article

Kent，L.N。＆Leone，G。破碎的周期：癌症中的E2F功能障碍。《国家癌症评论》19326-338（2019）。文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Baldominos, P. et al. Quiescent cancer cells resist T cell attack by forming an immunosuppressive niche. Cell 185, 1694–1708 (2022).Article

Baldominos，P。等人。静止的癌细胞通过形成免疫抑制生态位来抵抗T细胞攻击。细胞1851694-1708（2022）。文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Seiler, R. et al. Divergent biological response to neoadjuvant chemotherapy in muscle-invasive bladder cancer. Clin. Cancer Res. 25, 5082–5093 (2019).Article

Seiler，R.等。肌肉浸润性膀胱癌对新辅助化疗的不同生物学反应。临床。癌症研究255082-5093（2019）。文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Schulz, K. F., Altman, D. G., Moher, D. & CONSORT Group CONSORT 2010 statement: updated guidelines for reporting parallel group randomised trials. BMJ 340, c332–c332 (2010).Article

Schulz，K.F.，Altman，D.G.，Moher，D。＆CONSORT Group CONSORT 2010声明：报告平行组随机试验的更新指南。BMJ 340，c332–c332（2010）。文章

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Landrum, M. J. et al. ClinVar: improving access to variant interpretations and supporting evidence. Nucleic Acids Res. 46, D1062–D1067 (2018).Article

Landrum，M.J.等人，ClinVar：改进对变体解释和支持证据的获取。核酸研究46，D1062–D1067（2018）。文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Adzhubei, I. A. et al. A method and server for predicting damaging missense mutations. Nat. Methods 7, 248–249 (2010).Article

。自然方法7248-249（2010）。文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Liberzon, A. et al. The molecular signatures database hallmark gene set collection. Cell Syst. 1, 417–425 (2015).Article

Liberzon，A。等人。分子特征数据库hallmark gene set collection。细胞系统。1417-425（2015）。文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Aran, D., Hu, Z. & Butte, A. J. xCell: digitally portraying the tissue cellular heterogeneity landscape. Genome Biol. 18, 220 (2017).Article

Aran，D.，Hu，Z.＆Butte，A.J.xCell：数字描绘组织细胞异质性景观。基因组生物学。18220（2017）。文章

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Yoshihara, K. et al. Inferring tumour purity and stromal and immune cell admixture from expression data. Nat. Commun. 4, 2612 (2013).Article

Yoshihara，K。等人。从表达数据推断肿瘤纯度以及基质和免疫细胞混合物。国家公社。42612（2013）。文章

PubMed

PubMed

Google Scholar

谷歌学者

Li, S. et al. Molecular signatures of antibody responses derived from a systems biology study of five human vaccines. Nat. Immunol. 15, 195–204 (2014).Article

Li，S.等人。来自五种人类疫苗的系统生物学研究的抗体反应的分子特征。自然免疫。15195-204（2014）。文章

PubMed

PubMed

Google Scholar

谷歌学者

Chaussabel, D. et al. A modular analysis framework for blood genomics studies: application to systemic lupus erythematosus. Immunity 29, 150–164 (2008).Article

Chaussabel，D。等。血液基因组学研究的模块化分析框架：在系统性红斑狼疮中的应用。豁免29150-164（2008）。文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Zyla, J. et al. Gene set enrichment for reproducible science: comparison of CERNO and eight other algorithms. Bioinformatics 35, 5146–5154 (2019).Article

Zyla，J.等人，《可重复科学的基因集富集：CERNO和其他八种算法的比较》。生物信息学355146-5154（2019）。文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Simon, R. Optimal two-stage designs for phase II clinical trials. Controlled Clin. Trials 10, 1–10 (1989).Article

Simon，R。II期临床试验的最佳两阶段设计。受控临床。。文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Download referencesAcknowledgementsThis trial was supported by the National Key Research and Development Program of China (2018YFA0902800), the National Natural Science Foundation of China (81825016, 82341018 and U21A20383) and Sun Yat-Sen Memorial Hospital Clinical Research 5010 Program (SYS-5010Z-202401) to T.L., the National Natural Science Foundation of China (82173230 and 81961128027) to J.H., the National Natural Science Foundation of China (82173088), the Natural Science Foundation of Guangdong (2022A1515012383) and research funding of Sun Yat-sen University (23ptpy168) to K.L., the National Natural Science Foundation of China (82373254) to W.Z.

下载参考文献致谢本试验得到了国家重点研究发展计划（2018YFA0902800）、国家自然科学基金（8182501682341018和U21A20383）和中山纪念医院临床研究5010计划（SYS-5010Z-202401）的支持，国家自然科学基金（82173230和81961128027）的支持，国家自然科学基金（82173088）、广东自然科学基金（2022A1515012383）和中山大学研究基金（23ptpy168）的支持，国家自然科学基金（82373254）授予W.Z。

and the Guangdong Provincial Clinical Research Center for Urological Diseases (2020B1111170006). BeiGene (Beijing, China) provided tislelizumab free of charge and financial support for the procurement of gemcitabine and cisplatin, as well as biomarker analysis. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.

和广东省泌尿系统疾病临床研究中心（2020B1111170006）。BeiGene（中国北京）为吉西他滨和顺铂的采购以及生物标志物分析免费提供tislelizumab和财务支持。资助者在研究设计，数据收集和分析，决定发表或准备稿件方面没有任何作用。

L. Ling from the Department of Medical Statistics, School of Public Health, Sun Yat-Sen University provided statistical assistance. K. Zhang from the Ivy Medical Editing (Shanghai, China) provided writing and editing assistance.Author informationAuthor notesThese authors contributed equally: Kaiwen Li, Wenlong Zhong.Authors and AffiliationsDepartment of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, ChinaKaiwen Li, Wenlong Zhong, Shaoxu Wu, Longhao Xu, Jian Huang & Tianxin LinGuangdong Provincial Clinical Research Center for Urological Diseases, Guangzhou, ChinaKaiwen Li, Wenlong Zhong, Shaoxu Wu, Jian Huang & Tianxin LinDepartment of Urology, First Affiliated Hospital of Xi’an Jiaotong University, .

五十、 中山大学公共卫生学院医学统计系的Ling提供了统计帮助。K、 常春藤医学编辑（中国上海）的张提供了写作和编辑协助。。作者和附属机构中山大学中山纪念医院泌尿外科，广州，中国李开文，钟文龙，吴少旭，徐龙浩，黄健和天心林光东省泌尿系统疾病临床研究中心，广州，中国李开文，钟文龙，吴少旭，黄健和天心林西安交通大学第一附属医院泌尿科。

PubMed Google ScholarWenlong ZhongView author publicationsYou can also search for this author in

PubMed Google ScholarWenlong ZhongView作者出版物您也可以在

PubMed Google ScholarJinhai FanView author publicationsYou can also search for this author in

PubMed Google ScholarJinhai FanView作者出版物您也可以在

PubMed Google ScholarShaogang WangView author publicationsYou can also search for this author in

PubMed Google ScholarShaogang WangView作者出版物您也可以在

PubMed Google ScholarDexin YuView author publicationsYou can also search for this author in

PubMed Google ScholarDexin YuView作者出版物您也可以在

PubMed Google ScholarTao XuView author publicationsYou can also search for this author in

PubMed Google ScholarTao XuView作者出版物您也可以在

PubMed Google ScholarJiaju LyuView author publicationsYou can also search for this author in

PubMed Google ScholarJiaju LyuView作者出版物您也可以在

PubMed Google ScholarShaoxu WuView author publicationsYou can also search for this author in

PubMed Google ScholarShaoxu WuView作者出版物您也可以在

PubMed Google ScholarTao QinView author publicationsYou can also search for this author in

PubMed Google ScholarZhuo WuView author publicationsYou can also search for this author in

PubMed Google ScholarZhuo WuView作者出版物您也可以在

PubMed Google ScholarLonghao XuView author publicationsYou can also search for this author in

PubMed Google ScholarLonghao XuView作者出版物您也可以在

PubMed Google ScholarKaijie WuView author publicationsYou can also search for this author in

PubMed Google ScholarKaijie WuView作者出版物您也可以在

PubMed Google ScholarZheng LiuView author publicationsYou can also search for this author in

PubMed Google ScholarZheng LiuView作者出版物您也可以在

PubMed Google ScholarZhiquan HuView author publicationsYou can also search for this author in

PubMed Google ScholarZhiquan HuView作者出版物您也可以在

PubMed Google ScholarFan LiView author publicationsYou can also search for this author in

PubMed Google ScholarFan LiView作者出版物您也可以在

PubMed Google ScholarJinyou WangView author publicationsYou can also search for this author in

PubMed Google ScholarJinyou WangView作者出版物您也可以在

PubMed Google ScholarQi WangView author publicationsYou can also search for this author in

PubMed Google ScholarQi WangView作者出版物您也可以在

PubMed Google ScholarJie MinView author publicationsYou can also search for this author in

PubMed Google ScholarJie MinView作者出版物您也可以在

PubMed Google ScholarZhiqiang ZhangView author publicationsYou can also search for this author in

PubMed谷歌学者张志强查看作者出版物您也可以在

PubMed Google ScholarLuping YuView author publicationsYou can also search for this author in

PubMed Google ScholarLuping YuView作者出版物您也可以在

PubMed Google ScholarSentai DingView author publicationsYou can also search for this author in

PubMed谷歌学术网站DingView作者出版物您也可以在

PubMed Google ScholarLongfei HuangView author publicationsYou can also search for this author in

PubMed谷歌学者黄龙飞查看作者出版物您也可以在

PubMed Google ScholarTingting ZhaoView author publicationsYou can also search for this author in

PubMed Google ScholarTingting ZhaoView作者出版物您也可以在

PubMed Google ScholarJian HuangView author publicationsYou can also search for this author in

PubMed Google ScholarJian HuangView作者出版物您也可以在

PubMed Google ScholarTianxin LinView author publicationsYou can also search for this author in

PubMed Google Scholartiancin LinView作者出版物您也可以在

PubMed Google ScholarContributionsConceptualization and design, T.L., J.H., K.L. and W.Z. Administrative support: T.L. and J.H. Provision of study materials, K.L., J.F., S.Wang, D.Y., T.X., J.L., Z.L., K.W., J.W., Q.W., J.M., Z.H., F.L., Z.Z., L.Y., S.D., J.H. and T.L. Collection and assembly of data, K.L., J.F., S.

PubMed谷歌学术贡献概念与设计，T.L.，J.H.，K.L.和W.Z.行政支持：T.L.和J.H.提供研究材料，K.L.，J.F.，S.Wang，D.Y.，T.X.，J.L.，Z.L.，K.W.，J.W.，Q.W.，J.M.，Z.H.，F.L.，Z.Z.，L.Y.，S.D.，J.H.和T.L.数据收集和组装，K.L.，J.F.，S。

Wang, D.Y., T.X., J.L., T.Q., Z.L., K.W., J.W., Q.W., J.M., Z.H., F.L., Z.Z., L.Y., S.D., J.H. and T.L. Data analysis and interpretation, K.L., W.Z., J.F., S.Wang, D.Y., T.X., J.L., S.Wu, T.Q., Z.W., L.X., Z.L., K.W., J.W., Q.W., J.M., Z.H., F.L., Z.Z., L.Y., S.D., L.H., T.Z., J.H. and T.L. Manuscript writing, K.L., W.Z., J.H.

Wang，D.Y.，T.X.，J.L.，T.Q.，Z.L.，K.W.，J.W.，Q.W.，J.M.，Z.H.，F.L.，Z.Z.，L.Y.，S.D.，J.H.和T.L.数据分析和解释，K.L.，W.Z.，J.F.，S.Wang，D.Y.，T.X.，J.L.，S.Wu，T.Q.，Z.W.，L.X.，Z.L.，K.W.，J.W.，Q.W.，J.M.，Z.H.，F.L.，Z.，L.Y.，S.D.，L.H.，T.Z.，J.H.和T.L.手稿写作，K.L.，W.Z.，J.H。

and T.L. Accountable for all aspects of the work: T.L. and J.H. All authors read and approved the final version of the manuscript. T.L. and J.H. supervised all aspects of this work.Corresponding authorsCorrespondence to.

。T、 L.和J.H.监督了这项工作的各个方面。通讯作者通讯。

Jian Huang or Tianxin Lin.Ethics declarations

Jian Huang或Tianxin Lin.道德宣言

Competing interests

相互竞争的利益

L.H. and T.Z. were employees of GloriousMed at the time of the study. The other authors declare no competing interests.

五十、 在研究时，H.和T.Z.是GloriousMed的员工。其他作者声明没有利益冲突。

Peer review

同行评审

Peer review information

同行评审信息

Nature Cancer thanks Joaquim Bellmunt and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

《自然癌症》感谢JoaquimBellmunt和另一位匿名审稿人对这项工作的同行评审做出的贡献。

Additional informationPublisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.Extended dataExtended Data Fig. 1 Trial design and participant enrollment.a, The design of this trial; b, Flow of participants enrolled in this trial.Extended Data Fig.

Additional informationPublisher的注释Springer Nature在已发布的地图和机构隶属关系中的管辖权主张方面保持中立。扩展数据扩展数据图1试验设计和参与者登记。a，本试验的设计；b、 参加该试验的参与者流量。扩展数据图。

2 Comparison of response to neoadjuvant treatment by radiologic and pathologic assessment.a, Representative magnetic resonance imaging (MRI) images showing bladder tumor status in a cT3N0M0 patient, at the time of prior-cycle 1 and cycle 3 of neoadjuvant treatment, and prior-radical cystectomy, respectively.

2通过放射学和病理学评估比较对新辅助治疗的反应。a，代表性磁共振成像（MRI）图像显示cT3N0M0患者在新辅助治疗的前一周期和第三周期以及之前的根治性膀胱切除术时的膀胱肿瘤状态，分别。

This patient was evaluated as radiologic complete response (rCR) after neoadjuvant treatment and confirmed as pathologic complete response (pCR) after radical cystectomy. b, Comparison between rCR and pCR. ADC: apparent diffusion coefficient; DCE: dynamic contrast enhanced; DWI: diffusion weighted imaging; PD: progressive disease; T2WI: T2 weighted imaging.Source dataExtended Data Fig.

该患者在新辅助治疗后被评估为放射学完全缓解（rCR），并在根治性膀胱切除术后被证实为病理完全缓解（pCR）。b、 rCR和pCR之间的比较。ADC：表观扩散系数；DCE：动态对比度增强；DWI：扩散加权成像；PD：进行性疾病；T2WI:T2加权成像。源数据扩展数据图。

3 Swimmer plot with treatment, response and follow-up details for 57 patients undergoing radical cystectomy.Duration is relative to the date of first-dose neoadjuvant treatment. Clinical T/N stage is shown on the left side of the plot and displayed by bars with colors (green for T2N0M0, red for T3N0M0, and blue for T4aN0M0, respectively).

3游泳图，包括57例接受根治性膀胱切除术的患者的治疗，反应和随访细节。持续时间与第一剂新辅助治疗的日期有关。临床T/N分期显示在图的左侧，并用彩色条显示（T2N0M0为绿色，T3N0M0为红色，T4aN0M0为蓝色）。

Pathologic T/N stage after radical cystectomy is shown on the right side. Time points are marked by different shapes, including inverted triangle (last-dose of neoadjuvant treatment), triangle (last radiologic evaluation), diamond (radical cystectomy), circle (recurrence), cross (death), and arrow (continued follow-up).Source dataExtended Data Fig.

右侧显示根治性膀胱切除术后的病理T/N分期。时间点以不同的形状标记，包括倒三角形（最后一剂新辅助治疗），三角形（最后一次放射学评估），菱形（根治性膀胱切除术），圆形（复发），十字（死亡）和箭头（继续随访）。源数据扩展数据图。

4 Kaplan–Meier curves of event-free, overall survival (EFS and OS) and recurrence-f.

4无事件，总生存期（EFS和OS）和复发-f的Kaplan-Meier曲线。

Nat Cancer (2024). https://doi.org/10.1038/s43018-024-00822-0Download citationReceived: 09 December 2023Accepted: 09 August 2024Published: 10 September 2024DOI: https://doi.org/10.1038/s43018-024-00822-0Share this articleAnyone you share the following link with will be able to read this content:Get shareable linkSorry, a shareable link is not currently available for this article.Copy to clipboard.

Nat Cancer（2024）。https://doi.org/10.1038/s43018-024-00822-0Download引文收到日期：2023年12月9日接受日期：2024年8月9日发布日期：2024年9月10日OI：https://doi.org/10.1038/s43018-024-00822-0Share本文与您共享以下链接的任何人都可以阅读此内容：获取可共享链接对不起，本文目前没有可共享的链接。复制到剪贴板。

Provided by the Springer Nature SharedIt content-sharing initiative

由Springer Nature SharedIt内容共享计划提供