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Objective: To provide insight into the use and staging information on lymph-node involvement added by fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) in patients with muscle-invasive bladder cancer (MIBC), based on a nationwide population-based cohort study., Patients and Methods: We analysed a nationwide cohort of patients with MIBC without signs of distant metastases, newly diagnosed in the Netherlands between November 2017 and October 2019. From this cohort, we selected patients who underwent pre-treatment staging with CT only or CT and FDG-PET/CT. The distribution of patients, disease characteristics, imaging findings, nodal status (clinical nodal stage cN0 vs cN+) and treatment were described for each imaging modality group (CT only vs CT and FDG-PET/CT)., Results: We identified 2731 patients with MIBC: 1888 (69.1%) underwent CT only; 606 (22.2%) underwent CT and FDG-PET/CT, 237 (8.6%) underwent no CT. Of the patients who underwent CT only, 200/1888 (10.6%) were staged as cN+, vs 217/606 (35.8%) who underwent CT and FDG-PET/CT. Stratified analysis showed that this difference was found in patients with clinical tumour stage (cT)2 as well as cT3/4 MIBC. Of patients who underwent both imaging modalities and were staged with CT as cN0, 109/498 (21.9%) were upstaged to cN+ based on FDG-PET/CT. Radical cystectomy (RC) was the most common treatment within both imaging groups. Preoperative chemotherapy was more frequently applied in cN+ disease and in FDG-PET/CT-staged patients. Concordance of pathological N stage after upfront RC was higher among patients staged as cN+ with CT and FDG-PET/CT (50.0% pN+) than those staged as cN+ with only CT (39.3%)., Conclusion: Patients with MIBC who underwent pre-treatment staging with FDG-PET/CT were more often staged as lymph node positive, regardless of cT stage. In patients with MIBC who underwent CT and FDG-PET/CT, FDG-PET/CT led to clinical nodal upstaging in approximately one-fifth. Additional imaging findings may influence subsequent treatment strategies., (© 2023 The Authors. BJU International published by John Wiley & Sons Ltd on behalf of BJU International.)

Bladder cancer is among the ten most common cancers globally, causes considerable morbidity and mortality and is, therefore, a substantial burden for health-care systems. The incidence of bladder cancer is affected by demographic trends, most notably population growth and ageing, as well as exposure to risk factors, especially tobacco smoking. Consequently, the incidence has not been stable throughout the world over time, nor will it be in the near future. Further primary prevention efforts are of the utmost importance to reduce the medical and financial burden of bladder cancer on populations and health-care systems. Simultaneously, less-invasive and lower-cost approaches for the diagnosis of both primary and recurrent bladder cancers are required to address challenges posed by the increasing shortage of health-care professionals and limited financial resources worldwide. In this regard, urinary biomarkers have demonstrated promising diagnostic accuracy and efficiency. Awareness of the risk factors and symptoms of bladder cancer should also be increased in society, particularly among health-care professionals and high-risk groups. Studies investigating the associations between lifestyle factors and bladder cancer outcomes are scarce and should be a research priority. In this Review, we outline global trends in bladder cancer incidence and mortality, and discuss the main risk factors influencing bladder cancer occurrence and outcomes. We then discuss the implications, challenges and opportunities of these epidemiological trends for public health and clinical practice., (© 2023. Springer Nature Limited.)

Purpose: Bladder cancer (BC) is a common malignancy with well-established differences in incidence, clinical manifestation and outcomes between men and women. It is unknown to what extent disparities in outcomes are influenced by differences in treatment approaches. This paper describes treatment patterns among men and women with muscle-invasive BC focusing on curative treatment (radical cystectomy or trimodal therapy)., Methods: A retrospective population-based cohort study was performed with data from the Netherlands Cancer Registry. All patients newly diagnosed with muscle-invasive, non-advanced BC (MIBC, cT2-4a, N0/X, M0/X) in the years 2018, 2019 and 2020 were identified. Patient and tumor characteristics and initial treatment were compared between men and women with descriptive statistics and multivariable logistic regression analyses., Results: A total of 3484 patients were diagnosed with non-advanced MIBC in 2018-2020 in the Netherlands, of whom 28% were women. Women had higher T-stage and more often non-urothelial histology. Among all strata of clinical T-stage, women less often received treatment with curative intent (radical cystectomy [RC] or trimodality treatment). Among RC-treated patients, women more often received neoadjuvant treatment (except for cT4a disease). After adjustment for pre-treatment factors, odds ratios were indicative of women having lower probability of receiving curative treatment and RC specifically, and higher probability to receive NAC when treated with RC then men, although not statistically significant., Conclusions: Considerable differences in treatment patterns between men and women with MIBC exist. A more considerate role of the patient's sex in treatment decisions could help decrease these differences and might mitigate disparities in outcomes., (© 2022. The Author(s).)

Introduction: For many years EAU guidelines have recommended the use of cisplatin-based regimens over carboplatin for treatment of advanced urothelial cell carcinoma (UCC) in eligible patients. The claim of an overall survival (OS) benefit is based on (a meta-analysis of) 2 RCTs totalling 190 patients, of which one study has methodological flaws. These studies warrant secondary analysis to substantiate the evidence for an OS benefit of cisplatin- versus carboplatin-based regimens., Patients and Methods: Individual patient data (IPD) were reconstructed from the 2 RCTs, assessing OS in both treatment arms. IPD of both studies were then jointly reanalysed to assess an OS estimate with Kaplan-Meier methods, with, and without an alternative censoring scenario to assess the impact of the original biased censoring approach. Kaplan-Meier curves were compared by calculating restricted mean survival time (RMST) differences., Results: In each study individually, and in both studies combined, the survival benefit of cisplatin versus carboplatin was less than 1 month and not significant in a follow-up window of 12 months. This was also the case when an alternative censoring scenario was applied., Conclusion: Careful scrutiny of the data on which guidelines base the recommendation of cisplatin-based chemotherapy for the treatment of advanced UCC does not uphold the finding that cisplatin leads to an OS benefit when compared to carboplatin. This conclusion, combined with higher toxicity in cisplatin-based regimens warrants a reconsideration of this guideline recommendation., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Cisplatin is preferred to carboplatin when treating metastatic urothelial carcinoma of the bladder (mUCB), despite its greater toxicity. Randomised studies underpinning this have been performed in noncontemporary populations with limitations in sample sizes and analyses, affecting their validity in current clinical practice., Objective: To estimate overall survival (OS) and assess the benefit of cisplatin-based regimens over carboplatin-based regimens in a contemporary cohort of patients with mUCB., Design, Setting, and Participants: A nationwide retrospective cohort study was conducted in patients diagnosed with de novo mUCB in the Netherlands between 2016 and 2019, who underwent first-line treatment with cisplatin- or carboplatin-based chemotherapy, based on the data from the Netherlands Cancer Registry., Outcome Measurements and Statistical Analysis: A propensity model for receiving cisplatin-based chemotherapy based on age, sex, age-adjusted Charlson Comorbidity Index, renal function, performance status, serum haemoglobin, and the presence of visceral and bone metastases was used to produce inverse probability weighting (IPW) per patient. Unadjusted and IPW-adjusted Kaplan-Meier OS curves of both chemotherapy groups were compared by restricted mean survival time (RMST)., Results and Limitations: Of the 1041 patients with mUCB, 359 received either cisplatin (n = 170; 47%) or carboplatin (n = 189; 53%) as first line. The cisplatin group was younger, had fewer comorbidities, and had better performance status and renal function. The median OS in the cisplatin and carboplatin groups was 13.1 and 11.5 mo, respectively. After IPW adjustment, prognostic factors were balanced between the two chemotherapy groups (standardised differences <0.1), and differences in RMST were <2.0 mo and not statistically significant up to 24 mo., Conclusions: After accounting for all known prognostic factors, we found no significant survival benefit for cisplatin over carboplatin as first-line chemotherapy in mUCB., Patient Summary: In this study, we compared the survival benefits of cisplatin- and carboplatin-based chemotherapy for patients with metastatic bladder cancer., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: To contribute to the debate regarding the minimum volume of radical cystectomies (RCs) that a hospital should perform by evaluating the association between hospital volume (HV) and postoperative mortality., Patients and Methods: Patients who underwent RC for bladder cancer between 1 January 2008 and 31 December 2018 were retrospectively identified from the Netherlands Cancer Registry. To create a calendar-year independent measure, the HV of RCs was calculated per patient by counting the RCs performed in the same hospital in the 12 months preceding surgery. The relationship of HV with 30- and 90-day mortality was assessed by logistic regression with a non-linear spline function for HV as a continuous variable, which was adjusted for age, tumour, node and metastasis (TNM) stage, and neoadjuvant treatment., Results: The median (interquartile range; range) HV among the 9287 RC-treated patients was 19 (12-27; 1-75). Of all the included patients, 208 (2.2%) and 518 (5.6%) died within 30 and 90 days after RC, respectively. After adjustment for age, TNM stage and neoadjuvant therapy, postoperative mortality slightly increased between an HV of 0 and an HV of 25 RCs and steadily decreased from an HV of 30 onwards. The lowest risks of postoperative mortality were observed for the highest volumes., Conclusion: This paper, based on high-quality data from a large nationwide population-based cohort, suggests that increasing the RC volume criteria beyond 30 RCs annually could further decrease postoperative mortality. Based on these results, the volume criterion of 20 RCs annually, as recently recommended by the European Association of Urology Guideline Panel, might therefore be reconsidered., (© 2021 The Authors BJU International published by John Wiley & Sons Ltd on behalf of BJU International.)

Introduction: A better understanding of the molecular profile of bladder tumours, the identification of novel therapeutic targets, and introduction of new drugs and has renewed research interest in the field of bladder cancer. We describe the design and setup of a Dutch Prospective Bladder Cancer Infrastructure (ProBCI) as a means to stimulate and accelerate clinically meaningful experimental and observational research., Methods and Analysis: ProBCI entails an open cohort of patients with bladder cancer in which the trials within cohorts (TwiCs) design can be embedded. Physicians in participating hospitals prospectively recruit invasive (≥T1) patients with bladder cancer on primary diagnosis for inclusion into the study. Extensive clinical data are collected and updated every 4 months, along with patient-reported outcomes and biomaterials. Informed consent includes participation in TwiCs studies and renewed contact for future studies. Consent for participation in questionnaires and molecular analyses that may yield incidental findings is optional., Ethics and Dissemination: The Dutch ProBCI is a unique effort to construct a nation-wide cohort of patients with bladder cancer including clinical data, patient-reported outcomes and biomaterial, to facilitate observational and experimental research. Data and materials are available for other research groups on request through www.probci.nl. Ethics approval was obtained from METC Utrecht (reference: NL70207.041.19)., Trial Registration Number: NCT04503577., Competing Interests: Competing interests: NM reports grants and personal fees from Merck Sharp & Dohme, Roche, Janssen, AstraZeneca, grants from Sanofi and Pfizer, and personal fees from Astellas Pharma, Bristol-Myers Squibb, and Bayer outside the submitted work. JLB reports personal fees from Merck Sharp & Dohme, Roche and Janssen outside the submitted work. AGvdH reports personal fees from Merck Sharp & Dohme, Roche, Janssen, Sanofi, Ipsen Farmacuetica, Astellas Pharma and MML outside the submitted work. MSvdH reports grants and personal fees from Roche, Bristol-Myers Squibb and AstraZeneca, and personal fees from Merck Sharp & Dohme, Janssen, Astellas Pharma and Seattle Genetics outside the submitted work. AR, KKA, RPM and LAK have nothing to disclose., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Bladder cancer is among the top ten most common cancer types in the world, with approximately 550,000 new cases annually. The highest burden of bladder cancer is currently falling on most developed communities across the globe. But with an anticipated shift in world demographics with growing and aging populations mainly on the African continent, and important shifts in exposure to different risk factors across the world, this is likely to change over the next decades. In this review, we provide an overview of the current incidence, mortality, prevalence, survival, risk factors and costs of bladder cancer worldwide.

Background: With the introduction of new therapeutic options, the landscape of metastatic bladder cancer (mBC) management is shifting. We describe current clinical practice and outcomes of mBC patients as a benchmark for translation of developments into clinical practice in the near future., Patients and Methods: Nation-wide population-based cohort study including all patients diagnosed with synchronous metastatic bladder cancer in the Netherlands in 2016-2017, identified through the Netherlands Cancer Registry (NCR). Clinical data on patient and disease characteristics, treatments and survival from the NCR were supplemented with specific information from electronic health records and descriptively analyzed. This study was part of the Prospective Bladder Cancer Infrastructure., Results: Synchronous metastatic bladder cancer was diagnosed in 636 patients in the Netherlands in 2016 and 2017. 35% (221 patients) received systemic treatment, of whom 88 received multiple treatment lines. Most common first-line regimen was carboplatin-based chemotherapy (49%), followed by cisplatin-based chemotherapy (41%) and immunotherapy (8%). Factors associated with systemic treatment were: young age, <2 comorbidities, adequate renal function and performance-status (WHO-0-1/Karnofsky-80-100), urothelial carcinoma and lymph node only metastases. Median overall survival was 4.4 months for the total cohort, and 12.3, 12.9 and 11.1 months for patients treated with first-line immunotherapy, cisplatin-based and carboplatin-based chemotherapy, respectively., Conclusions: Many mBC patients received no systemic treatment or received carboplatin-based chemotherapy, partly because of cisplatin-ineligibility. Observed survival corresponded relatively well with rates reported from trials among chemotherapy-treated patients. These data can serve as a benchmark for future studies evaluating the application of immunotherapy outside a trial setting., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)