Background:Bladder cancer (BC) cell lines are indispensable in basic and preclinical research. Currently, an up-to-date and comprehensive overview of available BC cell lines is not available.Objective:To provide an overview and resources on the origin, pathological and molecular characteristics of commonly used human, murine and canine BC cell lines.Methods:A PubMed search was performed for relevant articles published between 1980 and 2017 according to the following MeSH terms: cell line; cell line, tumor; urinary bladder neoplasms; carcinoma, transitional cell. The Cellosaurus database was searched, using the term “bladder” and/or “urothelial carcinoma”. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.Results:We provide information on 157 human, murine and canine BC cell lines. 103 human BC cell lines have molecular data available, of which 69 have been profiled by at least one “omic” technology. We outline how these cell lines are currently being used for in vitro and in vivo experimental models. These results allow direct comparison of BC cell lines to patient samples, providing information needed to make informed decisions on the most genomically appropriate cell line to answer research questions. Furthermore, we show that cross-contamination remains an issue and describe guidelines for prevention.Conclusions:In the BC field, multiple human, murine and canine BC cell lines have been developed and many have become indispensable for in vitro and in vivo research. High-throughput -omic technologies have dramatically increased the amount of molecular data on these cell lines. We synthesized a comprehensive overview of these data as a resource for the BC scientific community.

Purpose: Currently, markers are lacking that can identify patients with high risk nonmuscle invasive bladder cancer who will fail bacillus Calmette-Gu erin treatment. Therefore, we evaluated the prognostic value of T1 substaging in patients with primary high risk nonmuscle invasive bladder cancer. Materials and Methods: Patients with primary high risk nonmuscle invasive bladder cancer who received !5 bacillus Calmette-Gu erin induction instillations were included. All tumors were centrally reviewed, which included T1 substaging (microinvasion vs extensive invasion of the lamina propria). T1 patients were stratified into high risk or highest risk subgroups according to major urology guidelines. Primary end point was bacillus Calmette-Gu erin failure, defined as development of a high grade recurrence. Secondary end points were high grade recurrence-free survival, defined as time from primary diagnosis to biopsyproven high grade recurrence and progression-free survival. Time-to-event analyses were used to predict survival. Results: A total of 264 patients with high risk nonmuscle invasive bladder cancer had tumor invasion of the lamina propria, of which 73% were classified as extensive invasion and 27% as microinvasion. Median followup was 68 months (IQR 43e98) and bacillus Calmette-Gu erin failure was more common among patients with extensive vs microinvasive tumors (41% vs 21%, p[0.002). The 3-year high grade recurrence-free survival (defined as bacillus Calmette-Guerin failure) for patients with extensive vs microinvasive tumors was 64% vs 83% (p[0.004). In multivariate analysis, T1 substaging was an independent predictor of high grade recurrence-free survival (HR 3.2, p[0.005) and progression-free survival (HR 3.0, p[0.009). Patients with highest risk/microinvasive disease have an improved progression-free survival as compared to highest risk/T1e disease (p.adj[0.038). Conclusions: T1 substaging provides important prognostic information on patients with primary high risk nonmuscle invasive bladder cancer treated with

The recommended treatment for patients with high-risk non–muscle-invasive bladder cancer (HR-NMIBC) is tumor resection followed by adjuvant Bacillus Calmette-Guérin (BCG) bladder instillations. However, only 50% of patients benefit from this therapy. If progression to advanced disease occurs, then patients must undergo a radical cystectomy with risks of substantial morbidity and poor clinical outcome. Identifying tumors unlikely to respond to BCG can translate into alternative treatments, such as early radical cystectomy, targeted therapies, or immunotherapies. Here, we conducted molecular profiling of 132 patients with BCG-naive HR-NMIBC and 44 patients with recurrences after BCG (34 matched), which uncovered three distinct BCG response subtypes (BRS1, 2 and BRS3). Patients with BRS3 tumors had a reduced recurrence-free and progression-free survival compared with BRS1/2. BRS3 tumors expressed high epithelial-to-mesenchymal transition and basal markers and had an immunosuppressive profile, which was confirmed with spatial proteomics. Tumors that recurred after BCG were enriched for BRS3. BRS stratification was validated in a second cohort of 151 BCG-naive patients with HR-NMIBC, and the molecular subtypes outperformed guideline-recommended risk stratification based on clinicopathological variables. For clinical application, we confirmed that a commercially approved assay was able to predict BRS3 tumors with an area under the curve of 0.87. These BCG response subtypes will allow for improved identification of patients with HR-NMIBC at the highest risk of progression and have the potential to be used to select more appropriate treatments for patients unlikely to respond to BCG.

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