Muscle-invasive Urothelial Cancer: Association of Mutational Status with with Metastatic Pattern and Survival
Muscle-invasive Urothelial Cancer: Association of Mutational Status with with Metastatic Pattern and Survival
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DOI：
10.1148/radiol.2020191770
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发表时间：
2020-06-01
期刊：
影响因子：
19.7
通讯作者：
Shinagare, Atul B.
中科院分区：
文献类型：
--
作者：
Alessandrino, Francesco;Williams, Kristin;Shinagare, Atul B.
背景：肌层浸润性尿路上皮癌（MIUC）的特点是大量的遗传异质性和高突变频率。最近已经证明了频繁突变的基因与临床行为之间的相关性。目的：探讨MIUC基因突变状态与肿瘤转移方式、无转移生存期（MFS）和总生存期（OS）的关系。材料与方法：这项单中心回顾性研究评估了连续的经活检证实的MIUC患者，这些患者接受了连续的横断面成像检查。（CT、MRI或氟18氟脱氧葡萄糖PET/CT）。使用卡方检验或Fisher精确检验，突变状态与转移部位相关。使用单变量考克斯比例风险模型将突变状态和转移模式与MFS和OS相关。高风险（存在TP 53、RB 1或KDM 6A突变）和低风险根据现有文献确定（存在ARID 1A、FGFR 3、PIK 3CA、STAG 2和/或TSC 1突变和不存在TP 53、RB 1或KDM 6A突变）组，并通过使用多变量考克斯比例风险模型与MFS和OS相关。对103名患者（平均年龄，72岁6 11 [标准差]; 81名男性）进行了评估。103例患者中有17例（16%）在诊断时患有转移性疾病; 103例患者中有38例（37%）在中位5.9个月（四分位距，0.8-28个月）时发生转移性疾病。tp 53突变（见于103例患者中的58例，56%）与淋巴结病相关（相对风险[RR]：1.7; 95%置信区间[CI]：1.2，2.4; P =.002）和骨转移（RR：1.9; 95% CI：1.6，2.3; P =.02）; RB 1突变（见于103例患者中的19例，18.4%）与腹膜癌转移相关（RR：5.9; 95% CI：3.8，9.2; P =.03）。ARID 1A突变与更高的OS相关（风险比[HR]：3.1; 95% CI：1.2，10; P =.01）。在多变量考克斯分析中，高危组（TP 53、RB 1和/或KDM 6A突变）与较短的MFS独立相关（HR：3.5，95%CI：1.3，12; P = 0.009）和更短的OS（HR：3.1; 95% CI：1.2，10; P =.02）。肌层浸润性尿路上皮癌的突变状态对转移模式、无转移生存率和总生存率有影响。(C)RSNA，2020年
Background: Muscle-invasive urothelial cancer (MIUC) is characterized by substantial genetic heterogeneity and high mutational frequency. Correlation between frequently mutated genes with clinical behavior has been recently demonstrated. Nonetheless, correlation between mutational status of MIUC and metastatic pattern is unknown.Purpose: To investigate the association of mutational status of MIUC with metastatic pattern, metastasis-free survival (MFS), and overall survival (OS).Materials and Methods: This single-center retrospective study evaluated consecutive patients with biopsy-proven MIUC who under-wentserial cross-sectional imaging (CT, MRI, or fluorine 18 fluorodeoxyglucose PET/CT) between April 2010 and December 2018. Mutational status was correlated with location of meta-stases using the chi(2) or Fisher exact test. Mutational status and metastatic pattern were correlated with MFS and OS using univariable Cox proportional hazard models. High-risk (presence of TP53, RB1, or KDM6A mutation) and low-risk (presence of ARID1A, FGFR3, PIK3CA, STAG2, and/or TSC1 mutation and absence of TP53, RB1, or KDM6A mutation) groups were determined according to existing literature and were correlated with MFS and OS by using multivariable Cox proportional hazard models.Results: One hundred three patients (mean age, 72 years 6 11 [standard deviation]; 81 men) were evaluated. Seventeen of 103 (16%) patients had metastatic disease at diagnosis; 38 of 103 (37%) developed metastatic disease at a median of 5.9 months (interquartile range, 0.8-28 months). TP53 mutation (seen in 58 of 103 patients, 56%) was associated with lymphadenopathy (relative risk [RR]: 1.7; 95% confidence interval [CI]: 1.2, 2.4; P =.002) and osseous metastases (RR: 1.9; 95% CI: 1.6, 2.3; P =.02); RB1 mutation (seen in 19 of 103 patients, 18.4%) was associated with peritoneal carcinomatosis (RR: 5.9; 95% CI: 3.8, 9.2; P =.03). ARID1A mutation was associated with greater OS (hazard ratio [HR]: 3.1; 95% CI: 1.2, 10; P =.01). At multivariable Cox analysis, the high-risk group (TP53, RB1, and/or KDM6A mutations) was independently associated with shorter MFS (HR: 3.5, 95%CI: 1.3, 12; P =.009) and shorter OS (HR: 3.1; 95% CI: 1.2, 10; P =.02).Conclusion: Mutational status of muscle-invasive urothelial cancer has implications on metastatic pattern, metastasis-free survival, and overall survival. (C) RSNA, 2020