Fibroblast Growth Factor Receptor 3 Alteration Status is Associated with Differential Sensitivity to Platinum-based Chemotherapy in Locally Advanced and Metastatic Urothelial Carcinoma.
Fibroblast Growth Factor Receptor 3 Alteration Status is Associated with Differential Sensitivity to Platinum-based Chemotherapy in Locally Advanced and Metastatic Urothelial Carcinoma.
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DOI：
10.1016/j.eururo.2020.07.018
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发表时间：
2020-12
期刊：
影响因子：
23.4
通讯作者：
Iyer G
中科院分区：
文献类型：
--
作者：
Teo MY;Mota JM;Whiting KA;Li HA;Funt SA;Lee CH;Solit DB;Al-Ahmadie H;Milowsky MI;Balar AV;Pietzak E;Dalbagni G;Bochner BH;Ostrovnaya I;Bajorin DF;Rosenberg JE;Iyer G
成纤维细胞生长因子受体3(FGFR3)的改变在约15%的肌肉浸润性膀胱癌(MIBCs)和转移性尿路上皮癌(MUC)中发生。目的：确定FGFR3状态与MIBC或MUC患者铂类化疗反应之间的关系。作者对(1)接受新辅助化疗(NAC)的MIBC患者、(2)接受一线铂类化疗(M1队列)的MUC患者和(3)来自癌症基因组图谱(TCGA)的MIBC患者进行了回顾和比较。以铂为基础的化疗。比较3个队列中FGFR3基因突变患者(FGFR3alt)和无FGFR3野生型患者(FGFR3wt)的病理反应、无复发(RFS)或无进展(PFS)生存期和总生存期(OS)。72例NAC患者中有9例(13%)出现FGFR3ALT，其中无一例病理完全缓解，3例残留非MIBC(1例原位癌，2例PT1)。FGFR3alt与较短的RFS(风险比，2.74；p=0.044)相关，但与OS无关。在接受辅助化疗的TCGA患者(n=74)中，FGFR3ALT患者的RFS也较短。相反，在未接受化疗的TCGA患者中，FGFR3ALT与较长的RFS和OS相关。在M1组(FGFR3alt，n=27；FGFR3wt，n=81)中，FGFR3alt与较高的肺转移率和非区域性淋巴病变相关。尽管FGFR3alt患者的有效率较低(37%比49%；p=0.056)，但PFS和OS与FGFR3wt患者没有显著差异。FGFR3状态与以铂为基础的化疗的低反应有关，这可能促使探索非化疗方法来处理FGFR3ALT尿路上皮癌的围手术期处理。大约15%的膀胱癌存在成纤维细胞生长因子受体3(FGFR3)基因的突变。我们的发现表明，在接受了围手术期铂类化疗的肌肉浸润性膀胱癌患者中，FGFR3突变可能与较低的反应和较短的复发时间有关。FGFR3状态对转移性尿路上皮癌患者的化疗反应没有显著影响。
Alterations in fibroblast growth factor receptor 3 (FGFR3) occur in ~15% of muscle-invasive bladder cancers (MIBCs) and metastatic urothelial carcinomas (mUCs). To determine the association between FGFR3 status and response to platinum-based chemotherapy in patients with MIBC or mUC. The authors conducted a retrospective review and comparison of patients having (1) MIBC treated with neoadjuvant chemotherapy (NAC), (2) mUC treated with first-line platinum-based chemotherapy (M1 cohort), and (3) MIBC who were from The Cancer Genome Atlas (TCGA). Platinum-based chemotherapy. Pathologic response, recurrence-free (RFS) or progression-free (PFS) survival, and overall survival (OS) were compared between patients with FGFR3 alteration (FGFR3alt) and those without it (FGFR3 wild type [FGFR3wt]) in the three cohorts. Nine of 72 NAC patients (13%) had FGFR3alt, of whom none had pathologic complete response and three had residual non-MIBC (carcinoma in situ, n = 1; pT1, n = 2). FGFR3alt was associated with shorter RFS (hazard ratio, 2.74; p = 0.044) but not OS. Among TCGA patients who underwent adjuvant chemotherapy (n = 74), FGFR3alt patients had shorter RFS as well. Conversely, among chemotherapy-naive TCGA patients, FGFR3alt was associated with longer RFS and OS. In the M1 cohort (FGFR3alt, n = 27; FGFR3wt, n = 81), FGFR3alt was associated with higher rates of pulmonary metastases and nonregional lymphadenopathy. Despite lower response rates among FGFR3alt patients (37% vs 49%; p = 0.056), PFS and OS were not significantly different from FGFR3wt patients. FGFR3 status is associated with lower responses to platinum-based chemotherapy, which may prompt exploration of nonchemotherapeutic approaches for perioperative management of FGFR3alt urothelial cancers. Approximately 15% of bladder cancers harbor mutations in the fibroblast growth factor receptor 3 (FGFR3) gene. Our findings suggest that FGFR3 mutations might be associated with lower responses and shorter time to recurrence among patients with muscle-invasive bladder cancer who received perioperative platinum-based chemotherapy. FGFR3 status does not significantly impact response to chemotherapy among those with metastatic urothelial cancers.
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影响因子：
158.5
作者：
Grossman, HB;Natale, RB;Crawford, ED
通讯作者：
Crawford, ED
影响因子：
2.7
作者：
Xie, Xina;Lin, Jiatian;Tang, Aifa
通讯作者：
Tang, Aifa
DOI：
10.1016/j.urolonc.2013.07.015
发表时间：
2014-01-01
影响因子：
2.7
作者：
Sung, Ji-Youn;Sun, Jong-Mu;Kwon, Ghee Young
通讯作者：
Kwon, Ghee Young
影响因子：
11.5
作者：
Audenet, Francois;Isharwal, Sumit;Solit, David B.
通讯作者：
Solit, David B.
影响因子：
11.5
作者：
Nassar, Amin H.;Umeton, Renato;Kwiatkowski, David J.
通讯作者：
Kwiatkowski, David J.