SUMMARY
Sarcomatoid urothelial bladder cancer (SARC) displays a high propensity for distant metastasis and is associated with short survival. We report a comprehensive genomic analysis of 28 cases of SARC and 84 cases of conventional urothelial carcinoma (UC), with the TCGA cohort of 408 muscle- invasive bladder cancers serving as the reference. SARCs show a distinct mutational landscape, with enrichment of TP53, RB1, and PIK3CA mutations. They are related to the basal molecular subtype of conventional UCs and could be divided into epithelial-basal and more clinically aggressive mesenchymal subsets on the basis of TP63 and its target gene expression levels. Other analyses reveal that SARCs are driven by downregulation of homotypic adherence genes and dysregulation of the EMT network, and nearly half exhibit a heavily infiltrated immune phenotype. Our observations have important implications for prognostication and the development of more effective therapies for this highly lethal variant of bladder cancer.
Introduction: Neoadjuvant chemotherapy (NAC) prior to radical or partial cystectomy is considered the standard of care for eligible patients with muscle-invasive urothelial carcinoma. Despite guideline recommendations, adoption of NAC has historically been low, although prior studies have suggested that use is increasing. In this contemporary study, we examine trends in the use of NAC and explore factors associated with its receipt. Methods: We identified patients in the National Cancer Database who underwent radical or partial cystectomy for cT2-cT4N0M0 urothelial carcinoma from 2006-2014. The proportion of patients receiving NAC during each year was examined. Logistic regression models were used to evaluate clinical and socioeconomic factors associated with the receipt of NAC. Results: A total of 18 188 patients were identified who underwent radical or partial cystectomy for muscle-invasive bladder cancer. Overall, 3940 (21.7%) received NAC. We noted a significant increase in the use of NAC over time, from 9.7% in 2006 to 32.2% in 2014. Factors associated with lower use of NAC include older age, higher comorbidity score, lower cT stage, lower hospital radical cystectomy volume, treatment at a non-academic facility, lower patient income, and receipt of partial cystectomy (all p<0.001). Interestingly, neither sex nor race were associated with receipt of NAC. Conclusions: Use of NAC has increased significantly over time to a modest rate of 32%. However, disparities still exist in the receipt of NAC and future efforts aimed at mitigating these disparities are warranted.
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