From the Department of Imaging (F.A., K.W., R.G., A.B.S.) and Lank Center for Genitourinary Oncology (A.H.N., G.S.), Dana Farber Cancer Institute, Harvard Medical School, 450 Brookline Avenue, Boston, MA 02215; and Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass (F.A., K.W., R.G., S.G.S., A.B.S.).
Radiology. 2020 Jun;295(3):572-580. doi: 10.1148/radiol.2020191770. Epub 2020 Mar 31.
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 underwent serial cross-sectional imaging (CT, MRI, or fluorine 18 fluorodeoxyglucose PET/CT) between April 2010 and December 2018. Mutational status was correlated with location of metastases using the χ 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 , , or mutation) and low-risk (presence of , , , , and/or mutation and absence of , , or 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 ± 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). 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; = .002) and osseous metastases (RR: 1.9; 95% CI: 1.6, 2.3; = .02); mutation (seen in 19 of 103 patients, 18.4%) was associated with peritoneal carcinomatosis (RR: 5.9; 95% CI: 3.8, 9.2; = .03). mutation was associated with greater OS (hazard ratio [HR]: 3.1; 95% CI: 1.2, 10; = .01). At multivariable Cox analysis, the high-risk group (, , and/or mutations) was independently associated with shorter MFS (HR: 3.5, 95% CI: 1.3, 12; = .009) and shorter OS (HR: 3.1; 95% CI: 1.2, 10; = .02). Conclusion Mutational status of muscle-invasive urothelial cancer has implications on metastatic pattern, metastasis-free survival, and overall survival. © RSNA, 2020 See also the editorial by Choyke in this issue.
背景 肌层浸润性尿路上皮癌（MIUC）的特征是存在大量遗传异质性和高频突变。最近已经证明了经常发生突变的基因与临床行为之间存在相关性。然而，MIUC 的突变状态与转移模式之间的相关性尚不清楚。目的 研究 MIUC 的突变状态与转移模式、无转移生存（MFS）和总生存（OS）之间的关系。材料与方法 本单中心回顾性研究纳入了 2010 年 4 月至 2018 年 12 月期间连续接受活检证实的 MIUC 并接受了连续横断面影像学（CT、MRI 或氟 18 氟脱氧葡萄糖 PET/CT）检查的患者。使用 χ 或 Fisher 确切检验将突变状态与转移部位相关联。使用单变量 Cox 比例风险模型将突变状态和转移模式与 MFS 和 OS 相关联。根据现有文献确定高危（存在 、 或 突变）和低危（存在 、 、 、 和/或 突变且不存在 、 或 突变）组，并使用多变量 Cox 比例风险模型将其与 MFS 和 OS 相关联。结果 103 例患者（平均年龄 72 岁±11[标准差]；81 例男性）被评估。103 例患者中有 17 例（16%）在诊断时就存在转移性疾病；38 例（37%）在中位时间 5.9 个月（四分位距，0.8-28 个月）时发生了转移性疾病。58 例（56%）患者存在 突变，与淋巴结病（相对风险 [RR]：1.7；95%置信区间 [CI]：1.2，2.4； =.002）和骨转移（RR：1.9；95% CI：1.6，2.3； =.02）相关；19 例（18.4%）患者存在 突变，与腹膜癌病（RR：5.9；95% CI：3.8，9.2； =.03）相关。存在 突变（RR：3.1；95% CI：1.2，10； =.01）与 OS 更长相关。在多变量 Cox 分析中，高危组（ 、 或 突变）与 MFS 更短（HR：3.5，95% CI：1.3，12； =.009）和 OS 更短（HR：3.1；95% CI：1.2，10； =.02）独立相关。结论 MIUC 的突变状态对转移模式、无转移生存和总生存有影响。
