Introduction: Lymphovascular invasion (LVI) in invasive bladder cancer is strongly associated with metastatic disease. We aim to identify the genes that could be the potential drivers of LVI in non-metastatic lymph node negative muscle invasive bladder cancer (M0N0MIBC). Methods: We queried the American Association for Cancer Research Project Genomics Evidence Neoplasia Information Exchange (GENIE) registry. Key genes were identified in respect to LVI status in 316 patients with M0N0MIBC. The relationships among LVI-associated genomic subtypes, clinicopathological features and patient outcomes were explored. All patients had imaging and pathologic evaluation to ensure M0 and N0 status. We included frequency rates of > 5% and p/q values < 0.05 were considered statistically significant to maintain >95% true positive detection rate. SPSS V24 was used for analyses. Results: A total of 316 patients were included in our study cohort, all of which had M0N0MIBC disease. Overall, 112 (35.4%) patients had LVI-positive and 204 (64.6%) patients were LVI-negative. Male patients constituted the majority of the cohort [230 (72.8%)]. 248 men (78.5%) in the cohort were Caucasian. Median age was 70 years (65-75 IQR). At the time of the analysis, 312 (98%) patients had not received any systemic treatment. LVI was associated with a higher T stage and more aggressive grade ( p = 0.02). We identified alterations in 56 genes. Patients with LVI had significantly higher mutation alterations rate in 7 genes (p <0.001) - CDKN2A, CDKN2ADT, CDKN2B, MTAP, HMCN1, DMRTA1, KMT2D. There was downregulation of 3 genes - RB1, SOX4 and CDKAL1 among those with LVI (Fig 1). Patients with LVI had a shorter overall survival (p <0.001) and a shorter 5 year progression-free survival (p <0.001) (Fig 2). Conclusions: Imbalance between genetic expression of extracellular matrix components (HMCN1) and cell-cycle regulators (CDK family) could initiate LVI in association with disease progression in patients with N0M0MIBC. SOURCE OF Funding: none
