Muscle-invasive Urothelial Cancer: Association of Mutational Status with Metastatic Pattern and Survival

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 χ2 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 ± 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. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Choyke in this issue.