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© 2015 European Association of Urology. Context Given the highly variable behavior and clinical course of prostate cancer (PCA) and the multiple available treatment options, a personalized approach to oncologic risk stratification is important. Novel genetic approaches offer additional information to improve clinical decision making. Objective To review the use of genomic biomarkers in the prognostication of PCA outcome and prediction of therapeutic response. Evidence acquisition Systematic literature review focused on human clinical studies reporting outcome measures with external validation. The literature search included all Medline, Embase, and Scopus articles from inception through July 2014. Evidence synthesis An improved understanding of the genetic basis of prostate carcinogenesis has produced an increasing number of potential prognostic and predictive tools, such as transmembrane protease, serine2:v-ets avian erythroblastosis virus E26 oncogene homolog (TMPRSS2:ERG) gene fusion status, loss of the phosphatase and tensin homolog (PTEN) gene, and gene expression signatures utilizing messenger RNA from tumor tissue. Several commercially available gene panels with external validation are now available, although most have yet to be widely used. The most studied commercially available gene panels, Prolaris, Oncotype DX Genomic Prostate Score, and Decipher, may be used to estimate disease outcome in addition to clinical parameters or clinical nomograms. ConfirmMDx is an epigenetic test used to predict the results of repeat prostate biopsy after an initial negative biopsy. Additional future strategies include using genetic information from circulating tumor cells in the peripheral blood to guide treatment decisions at the initial diagnosis and at subsequent decision points. Conclusions Major advances have been made in our understanding of PCA biology in recent years. Our field is currently exploring the early stages of a personalized approach to augment traditional clinical decision making using commercially available genomic tools. A more comprehensive appreciation of value, limitations, and cost is important. Patient summary We summarized current advances in genomic testing in prostate cancer with a special focus on the estimation of disease outcome. Several commercial tests are currently available, but further understanding is needed to appreciate the potential benefits and limitations of these novel tests.

Social media use is becoming common in medical practice. Although primarily used in this context to connect physicians, social media allows users share information, to create an online profile, to learn and keep knowledge up to date, to facilitate virtual attendance at medical conferences, and to measure impact within a field. However, shared content should be considered permanent and beyond the control of its author, and typical boundaries, such as the patient-physician interaction, become blurred, putting both parties at risk. The European Association of Urology brought together a committee of stakeholders to create guidance on the good practice and standards of use of social media. These encompass guidance about defining an online profile; managing accounts; protecting the reputations of yourself and your organization; protecting patient confidentiality; and creating honest, responsible content that reflects your standing as a physician and your membership within this profession. © 2014 European Association of Urology.

Background and Objective: The 2024 US Food and Drug Administration approval of erdafitinib for the treatment of metastatic urothelial carcinoma (mUC) with FGFR3 alterations ushered in the era of targeted therapy for bladder cancer. In this review, we summarize the effects of FGFR pathway alterations in oncogenesis, clinical data supporting FGFR inhibitors in the management of bladder cancer, and the challenges that remain., Methods: Original articles relevant to FGFR inhibitors in urothelial cancer between 1995 and 2024 were systematically identified in the PubMed and MEDLINE databases using the search terms "FGFR" and "bladder cancer". An international expert panel with extensive experience in FGFR inhibitor treatment was convened to synthesize a collaborative narrative review., Key Findings and Limitations: Somatic FGFR3 alterations are found in up to 70% of low-grade non-muscle-invasive bladder cancers; these activate downstream signaling cascades and culminate in cellular proliferation. Beyond a link to lower-grade/lower-stage tumors, there is little consistency regarding whether these alterations confer prognostic risks for cancer recurrence or progression. FGFR3-altered tumors have been linked to a non-inflamed tumor microenvironment, but paradoxically do not seem to impact the response to systemic immunotherapy. Several pan-FGFR inhibitors have been investigated in mUC. With the introduction of novel intravesical drug delivery systems, FGFR inhibitors are poised to transform the therapeutic landscape for early-stage UC., Conclusions and Clinical Implications: With deepening understanding of the biology of bladder cancer, novel diagnostics, and improved drug delivery methods, we posit that FGFR inhibition will lead the way in advancing precision treatment of bladder cancer., (Copyright © 2024 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Objective: To report real-world outcomes for high-risk non-muscle-invasive bladder cancer (HRNMIBC), including bacillus Calmette-Guérin (BCG) and radical cystectomy (RC), as randomised comparisons of these have not been possible., Methods: We detail consecutive participants screened for the BRAVO randomised controlled trial comparing RC with BCG (International Standard Randomised Controlled Trial Number [ISRCTN]12509361). Patients were prospectively registered and case-note review used for outcomes. The primary outcome was overall survival. Secondary outcomes included recurrence, progression, metastasis, and bladder cancer-specific survival., Results and Limitations: A total of 193 patients were screened, including 106 (54.9%) who received BCG, 43 (22.3%) primary RC, 37 (19.2%) 'other' treatment and seven (3.6%) hyperthermic intravesical mitomycin C. All-cause death occurred in 55 (28.5%) patients at median (interquartile range [IQR]) of 29.0 (19.5-42.0) months. In multivariable analysis, overall mortality was more common in older patients (hazard ratio [HR] 2.63, 95% confidence interval [CI] 1.35-5.13; Cox P = 0.004 for age >70 years), those recruited from district hospitals (HR 0.53, 95% CI 0.3-0.95; P = 0.032) and those who did not undergo RC as their first treatment (HR 2.16, 95% CI 1.17-3.99; P = 0.014). In all, 17 (8.8%) patients died from bladder cancer (BC) at median (IQR) of 22.5 (19-36.25) months. In multivariable analysis, BC-specific mortality was more common in older patients (HR 4.87, 95% CI 1.1-21.6; P = 0.037) and those with Tis/T1 disease (HR 2.26, 95% CI 1.23-4.16; P = 0.008) but did not vary with initial treatment., Conclusions: Patients with HRNMIBC are at high-risk of mortality. Those choosing RC as their initial treatment have lower risks of mortality than others, although this may reflect fitness and selection., (© 2024 The Author(s). BJU International published by John Wiley & Sons Ltd on behalf of BJU International.)

Treatment options for recurrent high-risk non-muscle-invasive bladder cancer (HR NMIBC) and muscle-invasive bladder cancer (MIBC) are limited, highlighting a need for clinically effective, accessible, and better-tolerated alternatives. In this review we examine the clinical development program of TAR-200, a novel targeted releasing system designed to provide sustained intravesical delivery of gemcitabine to address the needs of patients with NMIBC and of those with MIBC. We describe the concept and design of TAR-200 and the clinical development of this gemcitabine intravesical system in the SunRISe portfolio of studies. This includes 3 phase I studies evaluating the safety and initial tumor activity of TAR-200 and 5 phase II/III studies assessing the efficacy and safety of TAR-200, with or without systemic cetrelimab, as a treatment option for patients with HR NMIBC (bacillus Calmette-Guérin naive [papillary and carcinoma in situ] and MIBC (neoadjuvant and patients ineligible for or refusing radical cystectomy). Pharmacokinetics demonstrate intravesical gemcitabine delivery via TAR-200 over a prolonged period without detectable plasma levels. Phase I studies showed that TAR-200 is well tolerated, with preliminary antitumor activity in intermediate-risk NMIBC and MIBC. Preliminary data from the phase IIb SunRISe-1 study demonstrate that TAR-200 monotherapy is safe and effective in patients with bacillus Calmette-Guérin-unresponsive high-risk NMIBC. TAR-200 represents an innovative approach to the local treatment of bladder cancer., Competing Interests: Declaration of competing interest Siamak Daneshmand has received grants/research funding and travel support from Photocure; consulting/advisory fees from Photocure, Pacific Edge, Ferring, Bristol Myers Squibb, Janssen, Johnson & Johnson, Protara, Urogen, Pfizer, CG Oncology, Vesica Health, and ImmunityBio; and has stock/other ownership interests in Taris. Ashish M. Kamat has served as a consultant for Abbott Molecular, Arquer, ArTara, Asieris, Astra Zeneca, BioClin Therapeutics, Biological Dynamics, Bristol Myers Squibb, Cepheid, Cold Genesys, Eisai, Engene, Ferring, FerGene, Imagin, Incyte DSMB, Janssen, MDxHealth, Medac, Merck, Pfizer, Photocure, ProTara, Roviant, Seattle Genetics, Sessen Bio, Theralase, TMC Innovation, US Biotest, and Urogen; and has contracted research with Adolor, Bristol Myers Squibb, FerGene, FKD Industries, Heat Biologics, Merck, Photocure, and SWOG/NIH and patents with CyPRIT (Cytokine Predictors of Response to Intravesical Therapy) Joint with UT MD Anderson Cancer Center. Neal D. Shore has received grants/research funding from AbbVie, Advantagene, Amgen, Aragon Pharmaceuticals, Astellas, AstraZeneca, Bayer, Boston Scientific, Bristol Myers Squibb, CG Oncology, Clovis Oncology, Dendreon, DisperSol, Endocyte, Exact Imaging, Exelixis, Ferring, FKD Therapies, Forma Therapeutics, Foundation Medicine, Genentech, Guardant Health, InVitae, Istari Oncology, Janssen, Jiansu Yahong Meditech, MDxHealth, Medivation, Merck, MT Group, Myovant Sciences, Myriad, Novartis, Nymox, OncoCellMDx, ORIC Pharmaceuticals, Pacific Edge, Palette Life Sciences, Plexxikon, Pfizer, Point Biopharma, Propella Therapeutics, RhoVac, Sanofi, Seattle Genetics, Sesen Bio, Steba Biotech, Theralase, Tolmar, Urogen, Urotronic, US Biotest, Vaxiion, Veru, and Zenflow; consulting/advisory fees from AbbVie, Amgen, Astellas, AstraZeneca, Bayer, Boston Scientific, Bristol Myers Squibb, CG Oncology, Clarity Pharmaceuticals, Clovis Oncology, Dendreon, Exact Imaging, FerGene, Ferring, Foundation Medicine, Genesis Cancer Care, Genzyme, InVitae, Janssen, Lantheus, Lilly, MDxHealth, Medivation, Myovant Sciences, Myriad Genetics, Nymox, Pacific Edge Biotechnology, Peerview, Pfizer, Phosphorus, Photocure, Propella Therapeutics, Sanofi, Sema4, Sesen Bio, Specialty Networks, Telix Pharmaceuticals, Tempus, Tolmar, Urogen, and Vaxiion; and honoraria/speaker fees from Astellas, AstraZeneca, Bayer, Clovis Oncology, Dendreon, Foundation Medicine, Guardant Health, Janssen, Merck, and Pfizer. Joshua J. Meeks has received honoraria from Astellas Pharma, AstraZeneca, Imvax, Incyte, Janssen, Merck, Pfirzer, Prokarium, Urogen Pharma; research funding from Epizyme and Merck Sharp & Dohme; has patents, royalties, or other intellectual property (institutional) : NMIBC classifier, TCGA classifier; and has a relationship (undefined) with Olympus. Matthew D. Galsky has served as a consultant for Abbvie Inc, Alligator, Astellas Pharma, AstraZeneca, Basilea, Bicycle, Bristol Myers Squibb, Curis, Dracen, Dragonfly, EMD Serono, FujiFilm Holdings America Corporation, Genentech, Gilead Sciences, GlaxoSmithKline, Incyte Corp, Janssen Biotech, Merck, Numab, Pfizer, Rappta Therapeutics, Seattle Genetics, and Veracyte. Joseph M. Jacob has received consulting or advisory fees from Janssen, Photocure, Urogen, and Verity Pharmaceuticals. Michiel S. van der Heijden has served as a consultant (paid to institution) for Astellas Pharma, AstraZeneca, Bristol Myers Squibb, Janssen, MSD Oncology, Pfizer, Roche, and Seagen; and has received institutional research funding from 4SC, AstraZeneca, Bristol Myers Squibb, and Roche. Stephen B. Williams has no disclosures to report. Thomas Powles has received consulting fees from Astellas, AstraZeneca, Bristol Myers Squibb, Eisai, Exelixis, Incyte, Ipsen, Johnson & Johnson, Mash Up Ltd, Merck Serono, MSD, Novartis, Pfizer, Roche, and Seattle Genetics; grant support from Astellas, AstraZeneca, Bristol Myers Squibb, Eisai, Exelixis, Ipsen, Johnson & Johnson, Merck Serono, MSD, Novartis, Pfizer, Seattle Genetics, and Roche; and support for attending meetings and/or travel from AstraZeneca, Ipsen, MSD, Pfizer, and Roche. Sam S. Chang has served as a consultant for ImmunityBio, Janssen, Merck, Pfizer, and Uro Urogen; Vanderbilt University Medical Center is a trial site for TAR-200. James W. F. Catto has received honoraria from AstraZeneca, Bristol Myers Squibb, and Roche; consultant fees from AstraZeneca, Bristol Myers Squibb, Ferring, Gilead Sciences, Ipsen, Janssen, QED Therapeutics, Photocure, Roche, and Steba Biotech; and institutional grants from Roche; has participated in a data safety monitoring board or advisory board for Bristol Myers Squibb; and is an unpaid trustee for Fight Bladder Cancer UK and Weston Park Cancer Charity. Sarah P. Psutka has had a consulting or advisory role with Janssen, Medtronic, and Merck; and has received honoraria from AstraZeneca. Félix Guerrero-Ramos has received grants/research funding from Combat Medical; consulting/advisory fees from AstraZeneca, Bristol Myers Squibb, Combat Medical, and Janssen; honoraria/speaker fees from Combat Medical, Janssen, and Pfizer; and travel support from Ipsen and Pfizer. Evanguelos Xylinas has received grants/research funding from Ferring; and consulting/advisory fees from Boston Scientific, Ipsen, Janssen Oncology, MSD, Astellas, AstraZeneca, and Bristol Myers Squibb. Makito Miyake has no disclosures to report. Giuseppe Simone has no disclosures to report. Karen Daniel, Hussein Sweiti, and Christopher Cutie are employees of Janssen Research & Development and may have stock/stock options with Johnson & Johnson. Andrea Necchi has served as a consultant or advisor for Astellas, AstraZeneca, Bayer, Bristol Myers Squibb, Incyte, Janssen, Merck, Pfizer, and Roche; and has received institutional grant support from Bristol Myers Squibb, Gilead Sciences, and Merck., (Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: Transurethral resection of bladder tumor (TURBT) is the initial staging procedure for new bladder cancers (BCs). For muscle-invasive bladder cancers (MIBCs), TURBT may delay definitive treatment. We investigated whether definitive treatment can be expedited for MIBC using flexible cystoscopic biopsy and multiparametric magnetic resonance imaging (mpMRI) for initial staging., Patients and Methods: We conducted a prospective open-label, randomized study conducted within 17 UK hospitals (registered as ISRCTN 35296862). Participants with suspected new BC were randomly assigned 1:1 to TURBT-staged or mpMRI-staged care, with minimization factors of sex, age, and clinician visual assessment of stage. Blinding was not possible. Patients unable/unwilling to undergo mpMRI or with previous BC were ineligible. The study had two stages with separate primary outcomes of feasibility and time to correct treatment (TTCT) for MIBC, respectively., Results: Between May 31, 2018, and December 31, 2021, 638 patients were screened, and 143 participants randomly assigned to TURBT (n = 72; 55 males, 15 MIBCs) or initial mpMRI (n = 71; 53 males, 14 MIBCs). For feasibility, 36 of 39 (92% [95% CI, 79 to 98]) participants with suspected MIBC underwent mpMRI. The median TTCT for participants with MIBC was significantly shorter with initial mpMRI (n = 12, 53 days [95% CI, 20 to 89] v n = 14, 98 days [95% CI, 72 to 125] for TURBT, log-rank P .02). There was no detriment for participants with non-MIBC (median TTCT: n = 30, 17 days [95% CI, 8 to 25] for mpMRI v n = 28, 14 days [95% CI, 10 to 29] for TURBT, log-rank P = .67). No serious adverse events were reported., Conclusion: The mpMRI-directed pathway led to a 45-day reduction in TTCT for MIBC. Incorporating mpMRI ahead of TURBT into the standard pathway was beneficial for all patients with suspected MIBC.

Background: Testing high-risk populations for non-visible haematuria may enable earlier detection of bladder cancer, potentially decreasing mortality. This research aimed to assess the cost-effectiveness of urine dipstick screening for bladder cancer in high-risk populations in England., Methods:  A microsimulation model developed in R software was calibrated to national incidence data by age, sex and stage, and validated against mortality data. Individual risk factors included age, sex, smoking status and factory employment. We evaluated three one-time screening scenarios: (1) current and former smokers of different ages within the 55-70 years range, (2) a mixed-age cohort of smokers aged 55-80 years and (3) individuals aged 65-79 years from high-risk regions. Probabilistic and scenario analyses evaluated uncertainty. The incremental cost-effectiveness ratio (ICER) was calculated and compared with the standard £20,000/quality-adjusted life year (QALY) threshold using payer's perspective and 2022 year of evaluation with 3.5% discounting for both costs and effects., Results:  Screening all current and former smokers (scenario 1) and both mixed-age cohorts (scenarios 2 and 3) was not cost-effective at the threshold of £20,000/QALY. Screening at age 58 years had a 33% probability of being cost-effective at £20,000/QALY threshold and a 64% probability at £30,000/QALY threshold. Screening current and former smoking men aged 58 and 60 years was cost-effective, with ICERs of £18,181 and £18,425 per QALY, respectively. Scenario results demonstrated the high impact of assumptions on lead time, diagnostic pathway, and screening efficacy on predictions., Conclusions:  Screening smoking men aged 58 or 60 years for bladder cancer using urine dipstick tests may be cost-effective., Competing Interests: Declarations. Conflict of Interest: The authors have no conflicts of interest besides being funded by the Yorkshire Cancer Research. Funding: This work was funded by Yorkshire Cancer Research (grant number RA/2019/R1/004: S431 Early detection of bladder cancer in Yorkshire: feasibility assessments for implementing a targeted study in populations with high disease specific mortality risk) and the Quality Research Policy Support Fund from the University of Sheffield. The funders have no impact on the study. Data availability: The microsimulation model is not publicly available owing to restrictions on the use of population data. However, the model code can be requested from the corresponding author for validation purposes. Authors’ contribution: O.M.: Conceptual modelling, R model design, analysis, manuscript writing. C.T.: Conceptual modelling, R model validation, manuscript revisions. E.A.: Analysis, manuscript revisions. J.T.: Funding acquisition, conceptual modelling, manuscript revisions. J.C.: Funding acquisition, conceptual modelling, manuscript revisions., (© 2025. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Neoadjuvant chemotherapy followed by radical cystectomy is the standard treatment for cisplatin-eligible patients with muscle-invasive bladder cancer. Adding perioperative immunotherapy may improve outcomes., Methods: In this phase 3, open-label, randomized trial, we assigned, in a 1:1 ratio, cisplatin-eligible patients with muscle-invasive bladder cancer to receive neoadjuvant durvalumab plus gemcitabine-cisplatin every 3 weeks for four cycles, followed by radical cystectomy and adjuvant durvalumab every 4 weeks for eight cycles (durvalumab group), or to receive neoadjuvant gemcitabine-cisplatin followed by radical cystectomy alone (comparison group). Event-free survival was one of two primary end points. Overall survival was the key secondary end point., Results: In total, 533 patients were assigned to the durvalumab group and 530 to the comparison group. The estimated event-free survival at 24 months was 67.8% (95% confidence interval [CI], 63.6 to 71.7) in the durvalumab group and 59.8% (95% CI, 55.4 to 64.0) in the comparison group (hazard ratio for progression, recurrence, not undergoing radical cystectomy, or death from any cause, 0.68; 95% CI, 0.56 to 0.82; P<0.001 by stratified log-rank test). The estimated overall survival at 24 months was 82.2% (95% CI, 78.7 to 85.2) in the durvalumab group and 75.2% (95% CI, 71.3 to 78.8) in the comparison group (hazard ratio for death, 0.75; 95% CI, 0.59 to 0.93; P = 0.01 by stratified log-rank test). Treatment-related adverse events of grade 3 or 4 in severity occurred in 40.6% of the patients in the durvalumab group and in 40.9% of those in the comparison group; treatment-related adverse events leading to death occurred in 0.6% in each group. Radical cystectomy was performed in 88.0% of the patients in the durvalumab group and in 83.2% of those in the comparison group., Conclusions: Perioperative durvalumab plus neoadjuvant chemotherapy led to significant improvements in event-free survival and overall survival as compared with neoadjuvant chemotherapy alone. (Funded by AstraZeneca; NIAGARA ClinicalTrials.gov number, NCT03732677; EudraCT number, 2018-001811-59.)., (Copyright © 2024 Massachusetts Medical Society.)

Background: Efforts to improve recovery after radical cystectomy (RC) are needed., Objective: To investigate wrist-worn wearable activity trackers in RC participants., Design, Setting, and Participants: An observational cohort study was conducted within the iROC randomised trial., Intervention: Patients undergoing RC at nine cancer centres wore wrist-based trackers for 7 days (d) at intervals before and after surgery., Outcome Measurements and Statistical Analysis: Step counts were compared with participant and operative features, and recovery outcomes., Results and Limitations: Of 308 participants, 284 (92.2%) returned digital activity data at baseline (median 17 d [interquartile range: 8-32] before RC), and postoperatively (5 [5-6] d) and at weeks 5 (43 [38-43] d), 12 (94 [87-106] d), and 26 (192 [181-205] d) after RC. Compliance was affected by the time from surgery and a coronavirus disease 2019 pandemic lockdown (return rates fell to 0-7%, chi-square p < 0.001). Step counts dropped after surgery (mean of 28% of baseline), before recovering at 5 weeks (wk) (71% of baseline) and 12 wk (95% of baseline; all analysis of variance [ANOVA] p < 0.001). Baseline step counts were not associated with postoperative recovery or death. Patients with extended hospital stays had reduced postoperative step counts, with a difference of 2.2 d (95% confidence interval: 0.856-3.482 d) between the lowest third and highest two-third tertiles (linear regression analysis; p < 0.001). Additionally, they spent less time out of the hospital within 90 d of RC (80.3 vs 74.3 d, p = 0.013). Lower step counts at 5, 12, and 26 wk were seen in those seeking medical help and needing readmission (ANOVA p ≤ 0.002)., Conclusions: Baseline step counts were not associated with recovery. Lower postoperative step counts were associated with longer length of stay at the hospital and postdischarge readmissions. Studies are required to determine whether low step counts can identify patients at a risk of developing complications., Patient Summary: Postoperative step counts appear to be a promising tool to identify patients in the community needing medical help or readmission. More work is needed to understand which measures are most useful and how best to collect these., (Copyright © 2023. Published by Elsevier B.V.)

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. POUT was a phase III, randomized, open-label trial, including 261 patients with muscle-invasive or lymph node-positive, nonmetastatic upper tract urothelial cancer (UTUC) randomly assigned after radical nephroureterectomy to platinum-based chemotherapy (132) or surveillance (129). Primary outcome analysis demonstrated that chemotherapy improved disease-free survival (DFS). At that time, the planned secondary outcome analysis of overall survival (OS) was immature. By February 2022, 50 and 67 DFS events had occurred in the chemotherapy and surveillance groups, respectively, at a median follow-up of 65 months. The 5-year DFS was 62% versus 45%, univariable hazard ratio (HR), 0.55 (95% CI, 0.38 to 0.80, P = .001). The restricted mean survival time (RMST) was 18 months longer (95% CI, 6 to 30) in the chemotherapy arm. There were 46 and 60 deaths in the chemotherapy and control arms, respectively. The 5-year OS was 66% versus 57%, with univariable HR, 0.68 (95% CI, 0.46 to 1.00, P = .049) and RMST difference 11 months (95% CI, 1 to 21). Treatment effects were consistent across chemotherapy regimens (carboplatin or cisplatin) and disease stage. Toxicities were similar to those previously reported, and there were no clinically relevant differences in quality of life between arms. In summary, although OS was not the primary outcome measure, the updated results add further support for the use of adjuvant chemotherapy in patients with UTUC, suggesting long-term benefits.

Uroplakins are a family of membrane-spanning proteins highly specific to the urothelium. There are four uroplakin proteins in humans. These are encoded by the following UPK genes: UPK1A , UPK1B , UPK2 and UPK3 Uroplakin proteins span the apical membrane of umbrella cells of the urothelium, where they associate into urothelial plaques. This provides a barrier function to prevent passage of urine across the urothelium in the renal pelvis, ureters, and bladder. Uroplakins are also involved in developmental processes such as nephrogenesis. The specific localisation of uroplakins within the urothelium means that they are often expressed in primary and metastatic urothelial cell carcinoma and may be used as an immunohistochemical marker of urothelial malignancy., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To describe the health-related quality of life (HRQoL) of patients in a prospective 12-month observational cohort study of new bladder cancer diagnoses and compare with national cancer and general population surveys., Patients and Methods: A prospective UK study in patients with new bladder cancer diagnoses at 13 NHS Trusts. The HRQoL data were collected at 3, 6, 9 and 12 months. Questionnaires used included: the EuroQoL five Dimensions (EQ-5D), European Organisation for Research and Treatment of Cancer quality of life questionnaire (EORTC QLQ)-30-item core, EORTC QLQ-24-item non-muscle-invasive bladder cancer, and EORTC QLQ-30-item muscle-invasive bladder cancer. Results were compared with the Cancer Quality of Life Survey and Health Survey for England., Results: A total of 349 patients were recruited, 296 (85%) completed the first (baseline) and 233 (67%) the final survey. The patients underwent transurethral resection of bladder tumour (TURBT) ± intravesical therapy (238 patients, 80%), radical cystectomy/radiotherapy (51, 17%) or palliation (seven, 2%). At baseline, patients needing radical treatment reported worse HRQoL including lower social function (74.2 vs 83.8, P = 0.002), increased fatigue (31.5 vs 26.1, P = 0.03) and more future worries (39.2 vs 29.4, P = 0.005) than patients who underwent TURBT. Post-treatment surveys showed no change/improvements for patients who underwent TURBT but deterioration for the radically treated cohort. At final survey, reports were similar to baseline, regardless of treatment. Radically treated patients continued to report poorer HRQoL including issues with body image (23.4 vs 12.5, P = 0.007) and male sexual function (75.8 vs 40.4, P < 0.001) compared to those who underwent TURBT. Radically treated patients reported lower EQ-5D utility scores and more problems with usual activities than the general population., Discussion: Patients undergoing TURBT can be reassured regarding HRQoL following treatment. However, those requiring radical treatment report greater changes in HRQoL with the need for appropriate clinical and supportive care to minimise the impact of treatments., (© 2023 The Authors. BJU International published by John Wiley & Sons Ltd on behalf of BJU International.)

Background: Academic and community urology centers participating in a pragmatic clinical trial in non-muscle-invasive bladder cancer completed monthly surveys assessing restrictions in aspects of bladder cancer care due to the COVID-19 Public Health Emergency. Our objective was to describe pandemic-related restrictions on bladder cancer care., Methods: We invited 32 sites participating in a multicenter pragmatic bladder cancer trial to complete monthly surveys distributed through REDCap beginning in May 2020. These surveys queried sites on whether they were experiencing restrictions in the use of elective surgery, transurethral resection of bladder tumors (TURBT), radical cystectomy, office cystoscopy, and intravesical bacillus Calmette-Guerin (BCG) availability. Responses were collated with descriptive statistics., Results: Of 32 eligible sites, 21 sites had at least a 50% monthly response rate over the study period and were included in the analysis. Elective surgery was paused at 76% of sites in May 2020, 48% of sites in January 2021, and 52% of sites in January 2022. Over those same periods, coinciding with COVID-19 incidence waves, TURBT was restricted at 10%, 14%, and 14% of sites, respectively, radical cystectomy was restricted at 10%, 14%, and 19% of sites, respectively, and cystoscopy was restricted at 33%, 0%, and 10% of sites, respectively., Conclusions: Bladder cancer care was minimally restricted compared with more pronounced restrictions seen in general elective surgeries during the COVID-19 pandemic., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Treatment options are limited for patients with high-risk non-muscle-invasive bladder cancer (NMIBC) with disease recurrence after bacillus Calmette-Guérin (BCG) treatment and who are ineligible for/refuse radical cystectomy. FGFR alterations are commonly detected in NMIBC. We evaluated the activity of oral erdafitinib, a selective pan-fibroblast growth factor receptor (FGFR) tyrosine kinase inhibitor, versus intravesical chemotherapy in patients with high-risk NMIBC and select FGFR3/2 alterations following recurrence after BCG treatment., Patients and Methods: Patients aged ≥18 years with recurrent, BCG-treated, papillary-only high-risk NMIBC (high-grade Ta/T1) and select FGFR alterations refusing or ineligible for radical cystectomy were randomized to 6 mg daily oral erdafitinib or investigator's choice of intravesical chemotherapy (mitomycin C or gemcitabine). The primary endpoint was recurrence-free survival (RFS). The key secondary endpoint was safety., Results: Study enrollment was discontinued due to slow accrual. Seventy-three patients were randomized 2 : 1 to erdafitinib (n = 49) and chemotherapy (n = 24). Median follow-up for RFS was 13.4 months for both groups. Median RFS was not reached for erdafitinib [95% confidence interval (CI) 16.9 months-not estimable] and was 11.6 months (95% CI 6.4-20.1 months) for chemotherapy, with an estimated hazard ratio of 0.28 (95% CI 0.1-0.6; nominal P value = 0.0008). In this population, safety results were generally consistent with known profiles for erdafitinib and chemotherapy., Conclusions: Erdafitinib prolonged RFS compared with intravesical chemotherapy in patients with papillary-only, high-risk NMIBC harboring FGFR alterations who had disease recurrence after BCG therapy and refused or were ineligible for radical cystectomy., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Recruitment and retention in cancer trials are long-standing issues, exacerbated by the COVID-19 pandemic. The UK National Institute of Health Research and leading clinicians have emphasised the urgency to achieve and surpass prepandemic levels of participation. Data from a recent UK trial demonstrated the impact of COVID-19 and highlighted factors that limited recruitment. In response to this worldwide problem, studies have identified strategies for remediation at the levels of funding, the research environment, study design and trial team-related aspects, yet evidence of progress is lacking. Equality, diversity and inclusivity have become central to UK health and social policy during the 2000s. The need for greater inclusivity in trials has become a particular concern for cancer researchers and funders in the UK and in the USA, in recognition of potential bias in results. In the UK trials, the lack of standardised recording of ethnicity data renders interpretation difficult and caution is required in comparisons with the USA. Recently, the focus of concern has shifted away from the impact of deprivation and low socioeconomic status on trial participation. Barriers created by these factors and their frequent intersection with ethnicity should not be overlooked. The UK has adopted an advisory approach to broadening recruitment, publishing policy documents, guidance and toolkits. In the USA, by contrast, action on inclusion is increasingly mandated. Within the UK paradigm, the cancer research community is strongly encouraged to adopt a coordinated approach towards standardised digital data collection and embed and evaluate innovative, cocreated, locally relevant strategies., Competing Interests: Competing interests: JWFC: Grants or contracts from any entity—Roche—payment to his employer and trials unit. Consulting fees—AstraZeneca; BMS; Gilead; QED Therapeutics; Roche; Ferring; Steba Biotech; UroGen; Janssen; Photocure—all payment to JWFC. Payment or honoraria for lectures, presentations, speakers, bureaus, manuscript writing or educational events—BMS; AstraZeneca; Roche—all payment to JWFC. Participation on a data safety monitoring board or advisory board—BMS—no payment. Leadership or fiduciary role in other board, society, committee or advocacy group—Fight Bladder Cancer UK—unpaid trustee. NDJ: all support for the present manuscript (eg, funding, provision of study materials, medical writing, article processing charges)—National Institute of Health and Care Research Health Technology Assessment programme, Project funding to the Cancer Research UK Clinical Trial Unit, University of Birmingham (Project no. 14/08/60). RTB: all support for the present manuscript (eg, funding, provision of study materials, medical writing, article processing charges)—BladderPath research funding to University of Birmingham, UK. Grants or contracts from any entity (all in list research funding to university of Birmingham, UK)—Cancer Research UK (Early Detection & Diagnosis); Cancer Research UK (Data Innovation Award); Janssen; University Hospitals Birmingham Charity, UK; Cancer Research UK (Biospecimen Collection); QED Therapeutics, USA; UroGen Pharma, USA; Cancer Research UK (Biomarker Project Award); Cancer Research UK (Early Detection Spark Award. Royalties or licences—Nonacus, UK—Diagnostic urinary biomarker royalties to University of Birmingham, UK. Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events—The Karolinska Institute, Sweden, Personal honorarium as PhD opponent. Patents planned, issued or pending—International patent application (PCT/GB2019/052776)—University of Oxford, UK & University of Birmingham, UK. Leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid—Action Bladder Cancer UK—unpaid trustee., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To report the NHS Digital (NHSD) data for patients diagnosed with kidney cancer (KC) in England. We explore the incidence, route to diagnosis (RTD), treatment, and survival patterns from 2013 to 2019., Materials and Methods: Data was extracted from the Cancer Data NHSD portal for International Classification of Diseases, 10th edition coded KC; this included Cancer Registry data, Hospital Episode Statistics, and cancer waiting times data., Results: Registrations included 66 696 individuals with KC. Incidence of new KC diagnoses increased (8998 in 2013, to 10 232 in 2019), but the age-standardised rates were stable (18.7-19.4/100 000 population). Almost half of patients (30 340 [45.5%]) were aged 0-70 years and the cohort were most frequently diagnosed with Stage 1-2 KC (n = 26 297 [39.4%]). Most patients were diagnosed through non-urgent general practitioner referrals (n = 16 814 [30.4%]), followed by 2-week-wait (n = 15 472 [28.0%]) and emergency routes (n = 11 796 [21.3%]), with older patients (aged ≥70 years), Stage 4 KCs, and patients with non-specified renal cell carcinoma being significantly more likely to present through the emergency route (all P < 0.001). Invasive treatment (surgery or ablation), radiotherapy, or systemic anti-cancer therapy use varied with disease stage, patient factors, and treatment network (Cancer Alliance). Survival outcomes differed by Stage, histological subtype, and social deprivation class (P < 0.001). Age-standardised mortality rates did not change over the study duration, although immunotherapy usage is likely not captured in this study timeline., Conclusion: The NHSD resource provides useful insight about the incidence, diagnostic pathways, treatment, and survival of patients with KC in England and a useful benchmark for the upcoming commissioned National Kidney Cancer Audit. The RTD data may be limited by incidental diagnoses, which could confound the high proportion of 'emergency' diagnoses. Importantly, survival outcomes remained relatively unchanged., (© 2023 The Authors. BJU International published by John Wiley & Sons Ltd on behalf of BJU International.)

Background: Little is known about contemporary lifestyle choices in patients with bladder cancer (BC). These choices include carcinogenic risk factors and could affect fitness to receive treatments., Objective: To evaluate the contemporary lifestyle choices in BC patients., Design, Setting, and Participants: Self-reported surveys from participants diagnosed with BC in the previous 10 yr captured smoking patterns, e-cigarette use, physical activity using the GODIN Leisure-Time Exercise Questionnaire, long-term conditions (LTCs), relationship status, sociodemographics, and body mass index (BMI; height and weight)., Outcome Measurements and Statistical Analysis: Findings were compared with the general population and men with prostate cancer., Results and Limitations: Completed surveys were received from 2092 participants. Most respondents were ex-smokers (61% vs 10% current vs 29% never). The use of e-cigarettes was uncommon (9%) and at lower rates than the age-equivalent general population. Passive smoke exposure was frequent (48%). Most participants (68%) were "insufficiently active" using the GODIN criteria and less physically active than the age-equivalent general population. Most respondents (44%) were classified as overweight (BMI 25-29.99) or obese (22%, BMI >30). Lifestyle factors varied with age, sex, socioeconomic deprivation, and LTCs. Younger participants were less likely to smoke (p < 0.001), more likely to have used e-cigarettes (p < 0.001), but more likely to have had passive smoke exposure (p = 0.008). Those from less affluent areas were more likely to smoke (p < 0.001), have used e-cigarettes (p < 0.001), and have had passive smoke exposure (p = 0.02). Females were less likely to be smokers (p < 0.001) but more likely to have been exposed to passive smoke (p < 0.001)., Conclusions: Persons affected by BC often have smoking exposures and high BMI, and are insufficiently active. Rates of e-cigarette use were lower than in the general population. Efforts to improve quality of life in this cohort should include wider advocation of smoking cessation, perhaps including the use of e-cigarettes, and programmes to increase exercise and reduce BMI., Patient Summary: We looked at the lifestyle choices, such as smoking, e-cigarette use, physical activity levels, and obesity, of patients following a bladder cancer diagnosis. We conclude that this population would benefit from healthy lifestyle interventions., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Context: Differences in recovery, oncological, and quality of life (QoL) outcomes between open radical cystectomy (ORC) and robot-assisted radical cystectomy (RARC) for patients with bladder cancer are unclear., Objective: This review aims to compare these outcomes within randomized trials of ORC and RARC in this context. The primary outcome was the rate of 90-d perioperative events. The secondary outcomes included operative, pathological, survival, and health-related QoL (HRQoL) measures., Evidence Acquisition: Systematic literature searches of MEDLINE, Embase, Web of Science, and clinicaltrials.gov were performed up to May 31, 2022., Evidence Synthesis: Eight trials, reporting 1024 participants, were included. RARC was associated with a shorter hospital length of stay (LOS; mean difference [MD] 0.21, 95% confidence interval [CI] 0.03-0.39, p = 0.02) than and similar complication rates to ORC. ORC was associated with higher thromboembolic events (odds ratio [OR] 1.84, 95% CI 1.02-3.31, p = 0.04). ORC was associated with more blood loss (MD 322 ml, 95% CI 193-450, p < 0.001) and transfusions (OR 2.35, 95% CI 1.65-3.36, p < 0.001), but shorter operative time (MD 76 min, 95% CI 39-112, p < 0.001) than RARC. No differences in lymph node yield (MD 1.07, 95% CI -1.73 to 3.86, p = 0.5) or positive surgical margin rates (OR 0.95, 95% CI 0.54-1.67, p = 0.9) were present. RARC was associated with better physical functioning or well-being (standardized MD 0.47, 95% CI 0.29-0.65, p < 0.001) and role functioning (MD 8.8, 95% CI 2.4-15.1, p = 0.007), but no improvement in overall HRQoL. No differences in progression-free survival or overall survival were seen. Limitations may include a lack of generalization given trial patients., Conclusions: RARC offers various perioperative benefits over ORC. It may be more suitable in patients wishing to avoid blood transfusion, those wanting a shorter LOS, or those at a high risk of thromboembolic events., Patient Summary: This study compares robot-assisted keyhole surgery with open surgery for bladder cancer. The robot-assisted approach offered less blood loss, shorter hospital stays, and fewer blood clots. No other differences were seen., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: Investigating the use of the EORTC bladder cancer (BC) modules by evaluating: (a) study contexts/designs; (b) languages/countries in which the modules were administered; (c) their acceptance by patients/investigators; and (d) their psychometric properties., Methods: A systematic review was performed with studies from 1998 until 20/10/2021 in five databases. Articles/conference abstracts using the EORTC-QLQBLM30 (muscle invasive BC) and the EORTC-QLQNMIBC24 (previously referred to as QLQ-BLS24; non-muscle invasive BC) were included. Two authors independently screened titles/abstracts/full-texts and performed data extraction., Results: A total of 76 eligible studies were identified. Most studies included the BLM30 (n = 53), were in a urological surgery context (n = 41) and were cross-sectional (n = 35) or prospective (n = 30) in design. The BC modules were administered in 14 languages across 19 countries. Missing data were low-moderate for all non-sex related questions (< 1% to 15%). Sex-related questions had higher rates of missing data (ranging from 6.9% to 84%). Most investigators did not use all scales of the questionnaires. One validation study for the original BLS24 led to the development of the NMIBC24, which adopted a new scale structure for which good structural validity was confirmed (n = 3). Good reliability and validity was shown for the NMIBC24 module, except for malaise and bloating/flatulence scales. Psychometric evidence for BLM30 is lacking., Conclusion: These results provide insight into how the EORTC BC quality of life modules could be further improved. Current work is ongoing to update the modules and to determine if the two modules can be combined into a single questionnaire that works well in both the NMIBC and MIBC settings., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Context: Bladder cancer (BC) is common worldwide and poses a significant public health challenge. External risk factors and the wider exposome (totality of exposure from external and internal factors) contribute significantly to the development of BC. Therefore, establishing a clear understanding of these risk factors is the key to prevention., Objective: To perform an up-to-date systematic review of BC's epidemiology and external risk factors., Evidence Acquisition: Two reviewers (I.J. and S.O.) performed a systematic review using PubMed and Embase in January 2022 and updated it in September 2022. The search was restricted to 4 yr since our previous review in 2018., Evidence Synthesis: Our search identified 5177 articles and a total of 349 full-text manuscripts. GLOBOCAN data from 2020 revealed an incidence of 573 000 new BC cases and 213 000 deaths worldwide in 2020. The 5-yr prevalence worldwide in 2020 was 1 721 000. Tobacco smoking and occupational exposures (aromatic amines and polycyclic aromatic hydrocarbons) are the most substantial risk factors. In addition, correlative evidence exists for several risk factors, including specific dietary factors, imbalanced microbiome, gene-environment risk factor interactions, diesel exhaust emission exposure, and pelvic radiotherapy., Conclusions: We present a contemporary overview of the epidemiology of BC and the current evidence for BC risk factors. Smoking and specific occupational exposures are the most established risk factors. There is emerging evidence for specific dietary factors, imbalanced microbiome, gene-external risk factor interactions, diesel exhaust emission exposure, and pelvic radiotherapy. Further high-quality evidence is required to confirm initial findings and further understand cancer prevention., Patient Summary: Bladder cancer is common, and the most substantial risk factors are smoking and workplace exposure to suspected carcinogens. On-going research to identify avoidable risk factors could reduce the number of people who get bladder cancer., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Little is known about the distal excretory component of the urinary tract in Danio rerio (zebrafish). This component is affected by many human diseases and disorders of development. Here, we have undertaken multi-level analyses to determine the structure and composition of the distal urinary tract in the zebrafish. In silico searches identified uroplakin 1a (ukp1a), uroplakin 2 (upk2) and uroplakin 3b (upk3b) genes in the zebrafish genome (orthologues to genes that encode urothelium-specific proteins in humans). In situ hybridization demonstrated ukp1a expression in the zebrafish pronephros and cloaca from 96 h post-fertilization. Haematoxylin and Eosin staining of adult zebrafish demonstrated two mesonephric ducts uniting into a urinary bladder that leads to a distinct urethral opening. Immunohistochemistry identified Uroplakin 1a, Uroplakin 2 and GATA3 expression in zebrafish urinary bladder cell layers that match human urothelial expression. Fluorescent dye injections demonstrated zebrafish urinary bladder function, including urine storage and intermittent micturition, and a urethral orifice separate from the larger anal canal and rectum. Our findings reveal homology between the urinary tracts of zebrafish and humans, and offer the former as a model system to study disease., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2023. Published by The Company of Biologists Ltd.)

Background and Objective: Bladder cancer is common among current and former smokers. High bladder cancer mortality may be decreased through early diagnosis and screening. The aim of this study was to appraise decision models used for the economic evaluation of bladder cancer screening and diagnosis, and to summarise the main outcomes of these models., Methods: MEDLINE via PubMed, Embase, EconLit and Web of Science databases was systematically searched from January 2006 to May 2022 for modelling studies that assessed the cost effectiveness of bladder cancer screening and diagnostic interventions. Articles were appraised according to Patient, Intervention, Comparator and Outcome (PICO) characteristics, modelling methods, model structures and data sources. The quality of the studies was also appraised using the Philips checklist by two independent reviewers., Results: Searches identified 3082 potentially relevant studies, which resulted in 18 articles that met our inclusion criteria. Four of these articles were on bladder cancer screening, and the remaining 14 were diagnostic or surveillance interventions. Two of the four screening models were individual-level simulations. All screening models (n = 4, with three on a high-risk population and one on a general population) concluded that screening is either cost saving or cost effective with cost-effectiveness ratios lower than $53,000/life-years saved. Disease prevalence was a strong determinant of cost effectiveness. Diagnostic models (n = 14) assessed multiple interventions; white light cystoscopy was the most common intervention and was considered cost effective in all studies (n = 4). Screening models relied largely on published evidence generalised from other countries and did not report the validation of their predictions to external data. Almost all diagnostic models (n = 13 out of 14) had a time horizon of 5 years or less and most of the models (n = 11) did not incorporate health-related utilities. In both screening and diagnostic models, epidemiological inputs were based on expert elicitation, assumptions or international evidence of uncertain generalisability. In modelling disease, seven models did not use a standard classification system to define cancer states, others used risk-based, numerical or a Tumour, Node, Metastasis classification. Despite including certain components of disease onset or progression, no models included a complete and coherent model of the natural history of bladder cancer (i.e. simulating the progression of asymptomatic primary bladder cancer from cancer onset, i.e. in the absence of treatment)., Conclusions: The variation in natural history model structures and the lack of data for model parameterisation suggest that research in bladder cancer early detection and screening is at an early stage of development. Appropriate characterisation and analysis of uncertainty in bladder cancer models should be considered a priority., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)