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Objective: To examine the disease-specific survival(DSS) after checkpoint inhibitor(CPI) therapy based on FGFR alterations and FGFR mRNA expression levels in patients with metastatic urothelial cancer(mUCa) within a multi-center cohort.Methods: Within a cohort of 72 patients with mUCa from five academic centers in Germany FGFR alterations, as well as FGFR1-4 mRNA expression levels in tumor samples from the primary tumor or metastatic sites. Spearman rank correlations, logistic regression, as well as Kaplan-Meier survival analyses and univariate Cox proportional hazards regression models were employed to examine the impact of different FGFR patterns on the DSS after CPI treatment.Results: FGFR3 mutations or gene fusions (gene alterations) were detected in 16.9% of all samples. Patients with or without FGFR3 gene alterations did not show different oncological outcomes undergoing CPI treatment. Low expression of FGFR2 mRNA alone, as well as the combination of either low FGFR2mRNA expression and FGFR3 gene alteration or high FGFR3mRNA expression (P = 0.027), identified a subgroup of patients with unfavorable outcomes, comprising 40% of the total cohort. This trend was also observed in univariate Cox proportional hazards regression analysis(FGFR3 gene alteration: Hazard ratio(HR) 5.33, 95%Confidence interval(CI)1.76-15.0, P = 0.004; FGFR3mRNA expression:HR 3.04, 95%CI 1.40-7.13, P = 0.005).Conclusion: Assessment of FGFR mRNA expression identified a high-risk subgroup of patients with mUCa. These patients showing overexpression of FGFR3 mRNA were found to have unfavorable DSS after CPI treatment. Using this approach may be suitable for identifying a patient population with poor response to CPI treatment, which may benefit from early FGFR inhibition. [ABSTRACT FROM AUTHOR]

Background: The impact of variant histologies on overall survival (OS), as well as their influence on the response to neoadjuvant and adjuvant chemotherapy (AC) is well studied in patients diagnosed with bladder cancer. However, little is known about tumors with variant histologies of the upper urinary tract. The objective of this study was to assess the survival of the predominant variant histologies of tumors of the renal pelvis (RPT) after surgical intervention, and to examine the influence of AC on the OS of the different variant histologies. Methods: We identified 21,318 patients with RPT undergoing surgical intervention using the National Cancer Database for the period 2004–2015. We employed multivariable Cox proportional hazards regression models and Kaplan–Meier curves to evaluate the OS according to variant histology. Separate multivariable Cox regression models were used to assess the specific effect of AC on OS of the histological subgroups. Results: The majority of patients were diagnosed with pure urothelial carcinoma (PUC) (96.1%). Overall, 826 patients were diagnosed with variant histologies (adenocarcinoma N = 298, squamous cell carcinoma N = 291, sarcomatoid N = 137, others N = 100). Compared to PUC, adenocarcinomas showed longer OS (HR 0.76, 95% confidence interval (CI) 0.62–0.94, p = 0.01), while sarcomatoid tumors had shorter OS (HR 1.59, 95% CI 1.12–2.26, p = 0.011). A subgroup analysis of patients undergoing AC showed a survival benefit in patients with PUC (HR 0.81, 95% CI 0.73–0.9, p < 0.001). Conclusion: We found that variant histologies of upper urinary tract carcinomas exhibit different survival rates and that AC was only associated with an OS benefit in patients with PUC. [ABSTRACT FROM AUTHOR]

When stratified by stage, there was a decrease in the incidence of localized (AAPC -1.6, 95% CI -1.9 to -1.3), regional (AAPC -1.3, 95% CI -1.8 to -0.9), and unstaged (AAPC -4.2, 95% CI -5.2 to -3.1) BCa over time. Abbreviations & Acronyms AAPC average annual percentage change BCa bladder cancer CI confidence interval SEER Surveillance, Epidemiology, and End Results BCa is often described as two distinct clinical entities. Incidence, survival and mortality rates of stage-specific bladder cancer in United States: A trend analysis. [Extracted from the article]