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Purpose: To understand readiness measures taken by oncologists to protect patients and health care workers from the novel coronavirus (COVID-19) and how their clinical decision making was influenced by the pandemic., Methods: An online survey was conducted between March 24 and April 29, 2020., Results: A total of 343 oncologists from 28 countries participated. The median age was 43 years (range, 29-68 years), and the majority were male (62%). At the time of the survey, nearly all participants self-reported an outbreak in their country (99.7%). Personal protective equipment was available to all participants, of which surgical mask was the most common (n = 308; 90%). Telemedicine, in the form of phone or video encounters, was common and implemented by 80% (n = 273). Testing patients with cancer for COVID-19 via reverse transcriptase polymerase chain reaction before systemic treatment was not routinely implemented: 58% reported no routine testing, 39% performed testing in selected patients, and 3% performed systematic testing in all patients. The most significant factors influencing an oncologist's decision making regarding choice of systemic therapy included patient age and comorbidities (81% and 92%, respectively). Although hormonal treatments and tyrosine kinase inhibitors were considered to be relatively safe, cytotoxic chemotherapy and immune therapies were perceived as being less safe or unsafe by participants. The vast majority of participants stated that during the pandemic they would use less chemotherapy, immune checkpoint inhibitors, and steroids. Although treatment in neoadjuvant, adjuvant, and first-line metastatic disease was less affected, most of the participants stated that they would be more hesitant to recommend second- or third-line therapies in metastatic disease., Conclusion: Decision making by oncologists has been significantly influenced by the ongoing COVID-19 pandemic.

Context: The coronavirus disease 2019 (COVID-19) pandemic is leading to delays in the treatment of many urologic cancers., Objective: To provide a contemporary picture of the risks from delayed treatment for urologic cancers to assist with triage., Evidence Acquisition: A collaborative review using literature published as of April 2, 2020., Evidence Synthesis: Patients with low-grade non-muscle-invasive bladder cancer are unlikely to suffer from a 3-6-month delay. Patients with muscle-invasive bladder cancer are at risk of disease progression, with radical cystectomy delays beyond 12 wk from diagnosis or completion of neoadjuvant chemotherapy. Prioritization of these patients for surgery or management with radiochemotherapy is encouraged. Active surveillance should be used for low-risk prostate cancer (PCa). Treatment of most patients with intermediate- and high-risk PCa can be deferred 3-6 mo without change in outcomes. The same may be true for cancers with the highest risk of progression. With radiotherapy, neoadjuvant androgen deprivation therapy (ADT) is the standard of care. For surgery, although the added value of neoadjuvant ADT is questionable, it may be considered if a patient is interested in such an approach. Intervention may be safely deferred for T1/T2 renal masses, while locally advanced renal tumors (≥T3) should be treated expeditiously. Patients with metastatic renal cancer may consider vascular endothelial growth factor targeted therapy over immunotherapy. Risks for delay in the treatment of upper tract urothelial cancer depend on grade and stage. For patients with high-grade disease, delays of 12 wk in nephroureterectomy are not associated with adverse survival outcomes. Expert guidance recommends expedient local treatment of testis cancer. In penile cancer, adverse outcomes have been observed with delays of ≥3 mo before inguinal lymphadenectomy. Limitations include a paucity of data and methodologic variations for many cancers., Conclusions: Patients and clinicians should consider the oncologic risk of delayed cancer intervention versus the risks of COVID-19 to the patient, treating health care professionals, and the health care system., Patient Summary: The coronavirus disease 2019 pandemic has led to delays in the treatment of patients with urologic malignancies. Based on a review of the literature, patients with high-grade urothelial carcinoma, advanced kidney cancer, testicular cancer, and penile cancer should be prioritized for treatment during these challenging times., (Copyright © 2020. Published by Elsevier B.V.)

Context: There is a lack of accepted consensus on what should constitute appropriate quality-of-care indicators for bladder cancer., Objective: To evaluate the optimal management of bladder cancer and propose quality indicators (QIs)., Evidence Acquisition: A systematic review was performed to identify literature on current optimal management and potential quality indicators for both non-muscle-invasive (NMIBC) and muscle-invasive (MIBC) bladder cancer. A panel of experts was convened to select a recommended list of QIs., Evidence Synthesis: For NMIBC, preoperative QIs include tobacco cessation counselling and appropriate imaging before initial transurethral resection of bladder tumour (TURBT). Intraoperative QIs include administration of antibiotics, proper safe conduct of TURBT using a checklist, and performing restaging TURBT with biopsy of the prostatic urethra in appropriate cases. Postoperative QIs include appropriate receipt of perioperative adjuvant therapy, risk-stratified surveillance, and appropriate decision to change therapy when indicated (eg, bacillus Calmette-Guerin [BCG] unresponsive). For MIBC, preoperative QIs include multidisciplinary care, selection for candidates for continent urinary diversion, receipt of neoadjuvant cisplatin-based chemotherapy, time to commencing radical treatment, consideration of trimodal therapy as a bladder-sparing alternative in select patients, preoperative counselling with stoma marking, surgical volume of radical cystectomy, and enhanced recovery after surgery protocols. Intraoperative QIs include adequacy of lymphadenectomy, blood loss, and operative time. Postoperative QIs include prospective standardised monitoring of morbidity and mortality, negative surgical margins for pT2 disease, appropriate surveillance after primary treatment, and adjuvant cisplatin-based chemotherapy in appropriate cases. Participation in clinical trials was highlighted as an important component indicating high quality of care., Conclusions: We propose a set of QIs for both NMIBC and MIBC based on established clinical guidelines and the available literature. Although there is currently a lack of level 1 evidence for the benefit of implementing these QIs, we believe that the measurement of these QIs could aid in the improvement and benchmarking of optimal care for bladder cancer., Patient Summary: After a systematic review of existing guidelines and literature, a panel of experts has recommended a set of quality indicators that can help providers and patients measure and strive towards optimal outcomes for bladder cancer care., (Copyright © 2019 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Context: A noninvasive multiparametric magnetic resonance imaging (MRI)-based scoring system for predicting muscle-invasive bladder cancer (MIBC), the "Vesical Imaging Reporting and Data System" (VI-RADS), was recently developed by an international multidisciplinary panel. Since then, a few studies evaluating the value of VI-RADS for predicting MIBC have been published., Objective: To review the diagnostic performance of VI-RADS for the prediction of MIBC., Evidence Acquisition: PubMed and EMBASE databases were searched up to November 10, 2019. We included diagnostic accuracy studies using VI-RADS to predict MIBC using cystectomy or transurethral resection as the reference standard. Methodological quality was evaluated with Quality Assessment of Diagnostic Accuracy Studies-2. Sensitivity and specificity were pooled and plotted using hierarchical summary receiver operating characteristics (HSROC) modeling. Meta-regression analyses were done to explore heterogeneity., Evidence Synthesis: Six studies (1770 patients) were included. Pooled sensitivity and specificity were 0.83 (95% confidence interval [CI] 0.70-0.90) and 0.90 (95% CI 0.83-0.95), and the area under the HSROC curve was 0.94 (95% CI 0.91-0.95). Heterogeneity was present among the studies (Q = 29.442, p <  0.01; I 2  = 87.93%, and 90.99% for sensitivity and specificity). Meta-regression analyses showed that the number of patients (>205 vs ≤205), magnetic field strength (3 vs 1.5 T), T2-weighted image slice thickness (3 vs 4 mm), and VI-RADS cutoff score (≥3 vs ≥4) were significant factors affecting heterogeneity (p ≤  0.03)., Conclusions: VI-RADS shows good sensitivity and specificity for determining MIBC. Technical factors associated with MRI acquisition and cutoff scores need to be taken into consideration as they may affect performance., Patient Summary: A recently established noninvasive magnetic resonance imaging-based scoring system shows good diagnostic performance in detecting muscle-invasive bladder cancer., (Copyright © 2020 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

We should embrace social media, but cautiously. Remember that our brains need downtime, space, and creativity. Remember that the loudest voices are not the most correct and trust a person by their actions, not their opinions., (Copyright © 2019. Published by Elsevier B.V.)

Purpose of Review: Radical cystectomy is the definitive surgical treatment for aggressive bladder cancer. The robotic platform offers a new approach to radical cystectomy, but the benefits are unclear. This review examines the latest evidence, with a particular focus on developments in the last two years., Recent Findings: Prospective evaluations of open (ORC) and robot-assisted radical cystectomy (RARC) are emerging. The radical cystectomy in patients with bladder cancer trial reported in 2018 and demonstrated oncological noninferiority for both approaches and marginal shorter length of stays with RARC using an extracorporeal reconstruction. The trial confirmed prospective randomized comparisons are possible, and replicates observations from two earlier, smaller randomised controlled trials with longer follow-up. Although there has been significant traction to the intracorporeal approach to RARC, randomized trial evidence is awaited to show any benefit over ORC., Summary: New evidence alludes to the noninferiority of the robotic platform in radical cystectomy in comparison to open surgery. There is minimal evidence of a clinically meaningful benefit. Until this is addressed, ORC remains the gold standard for the definitive surgical management of bladder cancer.

Context: Non-visible haematuria (NVH) is a common finding and may indicate undiagnosed urological cancer. The optimal investigation of NVH is unclear, given the incidence of cancer and the public health implications of testing all individuals with this finding., Objective: We review contemporary literature to determine the association of NVH with the diagnosis of bladder cancer (BC), upper tract urothelial carcinoma (UTUC), and kidney cancer (KC)., Evidence Acquisition: A systematic review of original articles in English was completed in May 2019. Meta-analyses for the diagnostic accuracy of NVH and urine cytology were performed., Evidence Synthesis: We screened 1529 articles and selected 78 manuscripts that fulfilled our inclusion criteria for narrative synthesis. Forty manuscripts were eligible for a meta-analysis (reporting 19 193 persons). The likelihood of a urological cancer in patients with NVH increased with age (<1% in those aged <40yr), male sex, and cigarette smoking. Less than 1% of patients are found to have a urological cancer after a negative NVH evaluation. Cancer detection rates in individuals evaluated for NVH ranged from 0% to 16% for BC in 37 studies, 0% to 3.5% for UTUC in 30 studies, and 0% to 9.7% for KC in 29 studies. Substantial statistical heterogeneity was present for the meta-analysis of detection rates., Conclusions: We present an up-to-date review of the association of NVH with the diagnosis of BC, UTUC, and KC. Individuals with dipstick positive haematuria aged ≥40yr, who have had potential precipitating causes excluded, should undergo an evaluation. Re-evaluation of patients with unremarkable initial investigations should be performed in high-risk patients or if new symptoms occur., Patient Summary: One in five people have microscopic traces of blood in their urine. This is an important indicator of urological cancer. Investigating all patients is uncomfortable and expensive. We evaluate the risk of cancer and estimate risks to groups of individuals., (Copyright © 2019 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: Urothelial carcinomas of the upper urinary tract (UTUCs) are rare, with poorer stage-for-stage prognosis than urothelial carcinomas of the urinary bladder. No international consensus exists on the benefit of adjuvant chemotherapy for patients with UTUCs after nephroureterectomy with curative intent. The POUT (Peri-Operative chemotherapy versus sUrveillance in upper Tract urothelial cancer) trial aimed to assess the efficacy of systemic platinum-based chemotherapy in patients with UTUCs., Methods: We did a phase 3, open-label, randomised controlled trial at 71 hospitals in the UK. We recruited patients with UTUC after nephroureterectomy staged as either pT2-T4 pN0-N3 M0 or pTany N1-3 M0. We randomly allocated participants centrally (1:1) to either surveillance or four 21-day cycles of chemotherapy, using a minimisation algorithm with a random element. Chemotherapy was either cisplatin (70 mg/m 2 ) or carboplatin (area under the curve [AUC]4·5/AUC5, for glomerular filtration rate <50 mL/min only) administered intravenously on day 1 and gemcitabine (1000 mg/m 2 ) administered intravenously on days 1 and 8; chemotherapy was initiated within 90 days of surgery. Follow-up included standard cystoscopic, radiological, and clinical assessments. The primary endpoint was disease-free survival analysed by intention to treat with a Peto-Haybittle stopping rule for (in)efficacy. The trial is registered with ClinicalTrials.gov, NCT01993979. A preplanned interim analysis met the efficacy criterion for early closure after recruitment of 261 participants., Findings: Between June 19, 2012, and Nov 8, 2017, we enrolled 261 participants from 57 of 71 open study sites. 132 patients were assigned chemotherapy and 129 surveillance. One participant allocated chemotherapy withdrew consent for data use after randomisation and was excluded from analyses. Adjuvant chemotherapy significantly improved disease-free survival (hazard ratio 0·45, 95% CI 0·30-0·68; p=0·0001) at a median follow-up of 30·3 months (IQR 18·0-47·5). 3-year event-free estimates were 71% (95% CI 61-78) and 46% (36-56) for chemotherapy and surveillance, respectively. 55 (44%) of 126 participants who started chemotherapy had acute grade 3 or worse treatment-emergent adverse events, which accorded with frequently reported events for the chemotherapy regimen. Five (4%) of 129 patients managed by surveillance had acute grade 3 or worse emergent adverse events. No treatment-related deaths were reported., Interpretation: Gemcitabine-platinum combination chemotherapy initiated within 90 days after nephroureterectomy significantly improved disease-free survival in patients with locally advanced UTUC. Adjuvant platinum-based chemotherapy should be considered a new standard of care after nephroureterectomy for this patient population., Funding: Cancer Research UK., (Copyright © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Objective: To test the hypothesis that the baseline clinico-pathological features of the men with localized prostate cancer (PCa) included in the ProtecT (Prostate Testing for Cancer and Treatment) trial who progressed (n = 198) at a 10-year median follow-up were different from those of men with stable disease (n = 1409)., Patients and Methods: We stratified the study participants at baseline according to risk of progression using clinical disease stage, pathological grade and PSA level, using Cox proportional hazard models., Results: The findings showed that 34% of participants (n = 505) had intermediate- or high-risk PCa, and 66% (n = 973) had low-risk PCa. Of 198 participants who progressed, 101 (51%) had baseline International Society of Urological Pathology Grade Group 1, 59 (30%) Grade Group 2, and 38 (19%) Grade Group 3 PCa, compared with 79%, 17% and 5%, respectively, for 1409 participants without progression (P < 0.001). In participants with progression, 38% and 62% had baseline low- and intermediate-/high-risk disease, compared with 69% and 31% of participants with stable disease (P < 0.001). Treatment received, age (65-69 vs 50-64 years), PSA level, Grade Group, clinical stage, risk group, number of positive cores, tumour length and perineural invasion were associated with time to progression (P ≤ 0.005). Men progressing after surgery (n = 19) were more likely to have a higher Grade Group and pathological stage at surgery, larger tumours, lymph node involvement and positive margins., Conclusions: We demonstrate that one-third of the ProtecT cohort consists of people with intermediate-/high-risk disease, and the outcomes data at an average of 10 years' follow-up are generalizable beyond men with low-risk PCa., (© 2020 Crown copyright. BJU International published by John Wiley & Sons Ltd on behalf of BJU International.)

Background: Vesical Imaging Reporting and Data System (VI-RADS) score is adopted to provide preoperative bladder cancer (BCa) staging. Repeated transurethral resection of bladder tumor (Re-TURBT) is recommended in most of high-risk non-muscle-invasive bladder cancers (HR-NMIBCs) due to possibility of persistent/understaged disease after initial TURBT. No diagnostic tools able to improve patient's stratification for such recommendation exist., Objective: To (1) prospectively validate VI-RADS for discriminating between NMIBC and muscle-invasive bladder cancer (MIBC) at TURBT, and (2) evaluate the accuracy of VI-RADS for identifying HR-NMIBC patients who could avoid Re-TURBT and detecting those at higher risk for understaging after TURBT., Design, Setting, and Participants: Patients with BCa suspicion were offered multiparametric magnetic resonance imaging (mpMRI) before TURBT. According to VI-RADS, a cutoff of ≥3 to define MIBC was assumed. TURBT reports were compared with preoperative VI-RADS scores to assess accuracy of mpMRI for discriminating between NMIBC and MIBC. HR-NMIBC Re-TURBT reports were compared with preoperatively recorded VI-RADS scores to assess mpMRI accuracy in predicting Re-TURBT outcomes., Intervention: Multiparametric MRI of the bladder before TURBT., Outcome Measurements and Statistical Analysis: Sensitivity, specificity, positive (PPV) and negative (NPV) predictive values were calculated for mpMRI performance in patients undergoing TURBT and for HR-NMIBC patients candidate for Re-TURBT. Performance of mpMRI was assessed by receiver operating characteristic curve analysis. Ƙ statistics was used to estimate inter- and intrareader variability., Results and Limitations: A total of 231 patients were enrolled. Multiparametric MRI showed sensitivity, specificity, PPV, and NPV for discriminating NMIBC from MIBC at initial TURBT of 91.9% (95% confidence interval [CI]: 82.2-97.3), 91.1% (95% CI: 85.8-94.9), 77.5% (95% CI: 65.8-86.7), and 97.1% (95% CI: 93.3-99.1), respectively. The area under the curve (AUC) was 0.94 (95% CI: 0.91-0.97). Among HR-NMIBC patients (n=114), mpMRI before TURBT showed sensitivity, specificity, PPV, and NPV of 85% (95% CI: 62.1-96.8), 93.6% (95% CI: 86.6-97.6), 74.5% (95% CI: 52.4-90.1), and 96.6% (95% CI: 90.5-99.3) respectively, to identify patients with MIBC at Re-TURBT. The AUC was 0.93 (95% CI: 0.87-0.97)., Conclusions: VI-RADS is accurate for discriminating between NMIBC and MIBC. Within HR-NMIBC cases, VI-RADS could, in future, improve the selection of patients who are candidate for Re-TURBT., Patient Summary: We investigated the accuracy of Vesical Imaging Reporting and Data System (VI-RADS) score to asses bladder cancer staging before transurethral resection of bladder tumors, and we explored the performance of VI-RADS score as a future preoperative predictive tool for the selection of high-risk non-muscle-invasive bladder cancer patients who are candidate for undergoing early repeated transurethral resection of the primary tumor site., (Copyright © 2019 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: There is uncertainty in deferred active treatment (DAT) programmes, regarding patient selection, follow-up and monitoring, reclassification, and which outcome measures should be prioritised., Objective: To develop consensus statements for all domains of DAT., Design, Setting, and Participants: A protocol-driven, three phase study was undertaken by the European Association of Urology (EAU)-European Association of Nuclear Medicine (EANM)-European Society for Radiotherapy and Oncology (ESTRO)-European Association of Urology Section of Urological Research (ESUR)-International Society of Geriatric Oncology (SIOG) Prostate Cancer Guideline Panel in conjunction with partner organisations, including the following: (1) a systematic review to describe heterogeneity across all domains; (2) a two-round Delphi survey involving a large, international panel of stakeholders, including healthcare practitioners (HCPs) and patients; and (3) a consensus group meeting attended by stakeholder group representatives. Robust methods regarding what constituted the consensus were strictly followed., Results and Limitations: A total of 109 HCPs and 16 patients completed both survey rounds. Of 129 statements in the survey, consensus was achieved in 66 (51%); the rest of the statements were discussed and voted on in the consensus meeting by 32 HCPs and three patients, where consensus was achieved in additional 27 statements (43%). Overall, 93 statements (72%) achieved consensus in the project. Some uncertainties remained regarding clinically important thresholds for disease extent on biopsy in low-risk disease, and the role of multiparametric magnetic resonance imaging in determining disease stage and aggressiveness as a criterion for inclusion and exclusion., Conclusions: Consensus statements and the findings are expected to guide and inform routine clinical practice and research, until higher levels of evidence emerge through prospective comparative studies and clinical trials., Patient Summary: We undertook a project aimed at standardising the elements of practice in active surveillance programmes for early localised prostate cancer because currently there is great variation and uncertainty regarding how best to conduct them. The project involved large numbers of healthcare practitioners and patients using a survey and face-to-face meeting, in order to achieve agreement (ie, consensus) regarding best practice, which will provide guidance to clinicians and researchers., (Copyright © 2019. Published by Elsevier B.V.)

Objectives: To evaluate accuracy and inter-observer variability using Vesical Imaging-Reporting and Data System (VI-RADS) for discrimination between non-muscle invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC)., Methods: Between September 2017 and July 2018, 78 patients referred for suspected bladder cancer underwent multiparametric MRI of the bladder (mpMRI) prior to transurethral resection of bladder tumor (TURBT). All mpMRI were reviewed by two radiologists, who scored each lesion according to VI-RADS. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated for each VI-RADS cutoff. Receiver operating characteristics curves were used to evaluate the performance of mpMRI. The Ƙ statistics was used to estimate inter-reader agreement., Results: Seventy-five patients were included in the final analysis, 53 with NMIBC and 22 with MIBC. Sensitivity and specificity were 91% and 89% for reader 1 and 82% and 85% for reader 2 respectively when the cutoff VI-RADS > 2 was used to define MIBC. At the same cutoff, PPV and NPV were 77% and 96% for reader 1 and 69% and 92% for reader 2. When the cutoff VI-RADS > 3 was used, sensitivity and specificity were 82% and 94% for reader 1 and 77% and 89% for reader 2. Corresponding PPV and NPV were 86% and 93% for reader 1 and 74% and 91% for reader 2. Area under curve was 0.926 and 0.873 for reader 1 and 2 respectively. Inter-reader agreement was good for the overall score (Ƙ = 0.731)., Conclusions: VI-RADS is accurate in differentiating MIBC from NMIBC. Inter-reader agreement is overall good., Key Points: • Traditionally, the local staging of bladder cancer relies on transurethral resection of bladder tumor. • However, transurethral resection of bladder tumor carries a significant risk of understaging a cancer; therefore, more accurate, faster, and non-invasive staging techniques are needed to improve outcomes. • Multiparametric MRI has proved to be the best imaging modality for local staging; therefore, its use in suitable patients has the potential to expedite radical treatment when necessary and non-invasive diagnosis in patients with poor fitness.

Immune checkpoint inhibitors (ICIs) are now used routinely to treat advanced or metastatic urothelial and renal cell carcinoma, among other cancers. Furthermore, multiple trials are currently exploring their role in adjuvant, neoadjuvant, and noninvasive (eg, high-grade non-muscle-invasive bladder cancer) settings. Consequently, urologists are increasingly confronted with patients who are on, have recently received, or will be treated with ICI therapy. The care of these patients is likely to be shared between urologists and medical oncologists, with additional occasional support of other medical specialties. Therefore, it is important that urologists have good knowledge of immune-related side effects. Here, we provide advice on prevention, early diagnosis, and clinical management of the most relevant toxicities to strengthen urologists' insight and, thus, role in the multidisciplinary management in the new immunotherapy era. PATIENT SUMMARY: Immune therapy is a common treatment for many patients with advanced cancer. We describe common side effects of this treatment, and advise how they are best prevented and managed., (Copyright © 2019. Published by Elsevier B.V.)

Prostate cancer (PCa) is one of the first three causes of cancer mortality in Europe. Screening in asymptomatic men (aged 55-69yr) using prostate-specific antigen (PSA) is associated with a migration toward lower staged disease and a reduction in cancer-specific mortality. By 20yr after testing, around 100 men need to be screened to prevent one PCa death. While this ratio is smaller than for breast and colon cancer, the long natural history of PCa means many men die from other causes. As such, the nonselective use of PSA testing and radical treatments can lead to overdiagnosis and overtreatment. The European Association of Urology (EAU) supports measures to encourage appropriate PCa detection through PSA testing, while reducing overdiagnosis and overtreatment. These goals may be achieved using personalized risk-stratified approaches. For diagnosis, the greatest benefit from early detection is likely to come in men assessed using baseline PSA levels at the age of 45yr to individualize screening intervals. Multiparametric magnetic resonance imaging as well as risk calculators based on family history, ethnicity, digital rectal examination, and prostate volume should be considered to triage the need for biopsy, thus reducing the risk of overdiagnosis. For treatment, the EAU advocates balancing patient's life expectancy and cancer's mortality risk when deciding an approach. Active surveillance is encouraged in well-informed patients with low-risk and some intermediate-risk cancers, as it decreases the risks of overtreatment without compromising oncological outcomes. Conversely, the EAU advocates radical treatment in suitable men with more aggressive PCa. Multimodal treatment should be considered in locally advanced or high-grade cancers. PATIENT SUMMARY: Implementation of prostate-specific antigen (PSA)-based screening should be considered at a population level. Men at risk of prostate cancer should have a baseline PSA blood test (eg, at 45yr). The level of this test, combined with family history, ethnicity, and other factors, can be used to determine subsequent follow-up. Magnetic resonance imaging scans and novel biomarkers should be used to determine which men need biopsy and how any cancers should be treated., (Copyright © 2019 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: Prostate cancer incidence, treatment, and survival rates vary throughout the UK, but little is known about regional differences in quality of survival., Objective: To investigate variations in patient-reported outcomes between UK countries and English Cancer Alliances., Design, Setting, and Participants: A cross-sectional postal survey of prostate cancer survivors diagnosed 18-42mo previously., Outcome Measurements and Statistical Analysis: Urinary, bowel, and sexual problems and vitality were patient reported using the Expanded Prostate Cancer Index Composite (EPIC-26) questionnaire. General health was also self-assessed. Regional variations were identified using multivariable log-linear regression., Results and Limitations: A total of 35823 men responded, 60.8% of those invited. Self-assessed health was significantly lower than the UK average in Wales and Scotland. Respondents reported more urinary incontinence in Scotland, more urinary irritation/obstruction in Scotland and Northern Ireland (NI), poorer bowel function in Scotland and NI, worse sexual function in Scotland, and reduced vitality/hormonal function in Scotland, Wales, and NI. Self-assessed health was poorer than the English average in South Yorkshire and North-East and Cumbria, with more urinary incontinence in North-East and Cumbria and Peninsula, greater sexual problems in West Midlands, and poorer vitality in North-East and Cumbria and West Midlands. Limitations include difficulty identifying clinically significant differences and limited information on pretreatment conditions., Conclusions: Despite adjustment for treatment, and clinical and sociodemographic factors, quality of survival among prostate cancer survivors varied by area of residence. Adoption of best practice from areas performing well could support enhanced survival quality in poorer performing areas, particularly with regard to bowel problems and vitality, where clinically relevant differences were reported., Patient Summary: We conducted a UK-wide survey of patient's quality of life after treatment for prostate cancer. Outcomes were found to vary depending upon where patients live. Different service providers need to ensure that all prostate cancer patients receive the same follow-up care., (Copyright © 2019 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Guidelines advocate early re-resection for these cancers, although the benefits are unclear and the uniform need is questioned. Here, we compare the outcomes using a large single-center cohort., Objectives: To compare the outcomes of patients with high-grade non-muscle-invasive bladder cancer (BC) who underwent and who did not undergo re-resection following their initial treatment., Design, Setting, and Participants: We identified all eligible patients with a new diagnosis treated between 1994 and 2009 in Sheffield. We annotated these with hospital and registry records., Outcome Measurements and Statistical Analysis: Primary outcomes were disease-specific and overall survival. Secondary outcomes were the findings at re-resection, rates of muscle invasion, and radical treatment. Statistical tests were two tailed and significance defined as p<0.05., Results and Limitations: We identified 932 eligible patients, including 229(25%) who underwent re-resection within 12 wk and 234 (25%) within 3-6 mo after diagnosis. Clinicopathological criteria were similar in patients with and without re-resection. Histological findings on re-resection were no residual cancer in 91 (20%) and BC in 138 (30%: 15 low-grade and 85 high-grade non-muscle-invasive cancers, and 38 muscle-invasive cancers). Patients with re-resection were more frequently diagnosed with muscle invasion (126 [27%] vs 49 [11%], chi-square p<0.001) and more commonly underwent radical treatment (127 [27%] vs 35 [8%], p<0.001) than those without re-resection. A total of 207 patients died from BC, including 46 (22%) with and 161 (78%) without re-resection. Patients who underwent re-resection within 3 mo had significantly higher disease-specific (log rank p=0.009) and overall survival (p<0.001) survival compared with those who did not. Differences were present only for patients with pT1 cancer at diagnosis., Conclusions: Patients undergoing re-resection within 3 mo of diagnosis were more likely to have histologically identified muscle invasion, were more likely to undergo radical treatment, and had a higher survival rate. The differences were greatest in patients with lamina propria invasion, suggesting the potential to avoid in others. Limitations of our work include retrospective design and selection bias., Patient Summary: Patients undergoing re-resection after a diagnosis of high-grade non-muscle-invasive bladder cancer had higher disease-specific and overall survival rates due to more accurate diagnosis and appropriate subsequent radical treatment. Re-resection carries greatest benefit to patients with lamina propria invasion at diagnosis., (Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.)

Introduction: Little is known about the impact of bladder cancer (BC) and its treatments on health-related quality of life (HRQL). To date, most work has been small in scale or restricted to subsets of patients. Life and bladder cancer is a cross-sectional and longitudinal study collecting patient-reported outcomes within two distinct cohorts., Methods and Analysis: A longitudinal study will collect patient-reported outcomes at 3-monthly intervals from newly diagnosed patients. Eligible cases will be identified by recruiting hospitals and surveyed at baseline, 6, 9 and 12 months postdiagnosis to explore changes in outcomes over time. A separate cross-sectional cohort of patients diagnosed within the last 10 years across Yorkshire will be identified through cancer registration systems and surveyed once to explore longer-term HRQL in BC survivors. A comprehensive patient-reported outcome measure (PROM) has been developed using generic, cancer-specific and BC-specific instruments. The study will provide evidence about how useful these PROMs are in measuring BC patient HRQL. The outcome data will be linked with administrative health data (eg, treatment information from hospital data)., Ethics and Dissemination: The study has received the following approvals: Yorkshire and the Humber-South Yorkshire Research Ethics Committee (17/YH/0095), Health Research Authority Confidentiality Advisory Group (17/CAG/0054). Results will be made available to patients, funders, NHS Trusts, Clinical Commissioning Groups, Strategic Clinical Networks and other researchers., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ.)

Context: The centralization of cancer care is associated with better clinical outcomes and may be a method for optimizing value-based health care systems., Objective: To systematically review the literature regarding the impact of centralization of care on clinical outcomes for genitourinary malignancies., Evidence Acquisition: A systematic review was conducted using Ovid and MEDLINE to identify studies between 1970 and 2018 reporting on the centralization of care for genitourinary malignancies. Prospective and retrospective studies were screened., Evidence Synthesis: There were no published randomized control trials (RCTs) on the centralization of care for genitourinary malignancies. Twenty-two retrospective studies met inclusion criteria. Centralization of radical cystectomy was the most studied. Care for bladder cancer, prostate cancer, penile cancer, testicular cancer, and renal cancer was reportedly associated with better morbidity and survival outcomes for patients treated at high-volume centers. However, evidence of better outcomes for centralization of care remains limited for penile, renal, and testicular cancers owing to the paucity of data and/or the lower incidence of these genitourinary malignancies., Conclusions: Care for genitourinary malignancies by high-volume providers was associated with greater utilization of cancer surgery, lower morbidity, and better survival outcomes. Centralization of care was most appropriate for complex procedures such as radical cystectomy when interpreted in the context of survival outcomes. Further research is needed to address the impact of centralizing care for all urologic malignancies with consideration of the associated costs and patient-reported measures, including quality of life and patient experience., Patient Summary: We explored the evidence for moving major operations into larger centers. We focused on surgery for cancers of the bladder, prostate, testicle, penis, and kidney, and found that larger-volume hospitals had better survival outcomes and fewer complications when compared to smaller hospitals. The difference may be greatest for complex major surgeries such as radical cystectomy., (Copyright © 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Occupational and environmental exposure to cadmium is associated with the development of urothelial cancer. The metallothionein (MT) family of genes encodes proteins that sequester metal ions and modulate physiological processes, including zinc homeostasis. Little is known about the selectivity of expression of the different MT isoforms. Here, we examined the effect of cadmium exposure on MT gene and isoform expression by normal human urothelial (NHU) cell cultures. Baseline and cadmium-induced MT gene expression was characterized by next-generation sequencing and RT-PCR; protein expression was assessed by Western blotting using isoform-specific antibodies. Expression of the zinc transporter-1 ( SLC30A1 ) gene was also assessed. NHU cells displayed transcription of MT-2A , but neither MT-3 nor MT-4 genes. Most striking was a highly inducer-specific expression of MT-1 genes, with cadmium inducing transcription of MT-1A , MT-1G , MT-1H , and MT-1M . Whereas MT-1G was also induced by zinc and nickel ions and MT-1H by iron, both MT-1 A and MT-1M were highly cadmium-specific, which was confirmed for protein using isoform-specific antibodies. Protein but not transcript endured post-exposure, probably reflecting sequestration. SLC30A1 transcription was also affected by cadmium ion exposure, potentially reflecting perturbation of intracellular zinc homeostasis. We conclude that human urothelium displays a highly inductive profile of MT-1 gene expression, with two isoforms identified as highly specific to cadmium, providing candidate transcript and long-lived protein biomarkers of cadmium exposure.

Background: Little is known about the health-related quality of life (HRQOL) of men living with advanced prostate cancer. We report population-wide functional outcomes and HRQOL in men with all stages of prostate cancer and identify implications for health-care delivery., Methods: For this population-based study, men in the UK living 18-42 months after diagnosis of prostate cancer were identified through cancer registration data. A postal survey was administered, which contained validated measures to assess functional outcomes (urinary incontinence, urinary irritation and obstruction, bowel, sexual, and vitality and hormonal function), measured with the Expanded Prostate Cancer Index Composite short form (EPIC-26), plus questions about use of interventions for sexual dysfunction) and generic HRQOL (assessed with the 5-level EuroQol five dimensions questionnaire [EQ-5D-5L] measuring mobility, self-care, usual activities, pain or discomfort, and anxiety or depression, plus a rating of self-assessed health). Log-linear and binary logistic regression models were used to compare functional outcomes and HRQOL across diagnostic stages and self-reported treatment groups. Each model included adjustment for age, socioeconomic deprivation, and number of other long-term conditions., Findings: 35 823 (60·8%) of 58 930 men responded to the survey. Disease stage was known for 30 733 (85·8%) of 35 823 men; 19 599 (63·8%) had stage I or II, 7209 (23·4%) stage III, and 3925 (12·8%) stage IV disease. Mean adjusted EPIC-26 domain scores were high, indicating good function, except for sexual function, for which scores were much lower. Compared with men who did not receive androgen deprivation therapy, more men who received the therapy reported moderate to big problems with hot flushes (30·7% [95% CI 29·8-31·6] vs 5·4% [5·0-5·8]), low energy (29·4% [95% CI 28·6-30·3] vs 14·7% [14·2-15·3]), and weight gain (22·5%, 21·7-23·3) vs 6·9% [6·5-7·3]). Poor sexual function was common (81·0%; 95% CI 80·6-81·5), regardless of stage, and more than half of men (n=18 782 [55·8%]) were not offered any intervention to help with this condition. Overall, self-assessed health was similar in men with stage I-III disease, and although slightly reduced in those with stage IV cancer, 23·5% of men with metastatic disease reported no problems on any EQ-5D dimension., Interpretation: Men diagnosed with advanced disease do not report substantially different HRQOL outcomes to those diagnosed with localised disease, although considerable problems with hormonal function and fatigue are reported in men treated with androgen deprivation therapy. Sexual dysfunction is common and most men are not offered helpful intervention or support. Service improvements around sexual rehabilitation and measures to reduce the effects of androgen deprivation therapy are required., Funding: The Movember Foundation, in partnership with Prostate Cancer UK., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objective: To describe how clinicians conceptualised equipoise in the PART (Partial prostate Ablation vs Radical prosTatectomy in intermediate-risk unilateral clinically localised prostate cancer) feasibility study and how this affected recruitment., Subjects and Methods: PART included a QuinteT Recruitment Intervention (QRI) to optimise recruitment. Phase I aimed to understand recruitment, and included: scrutinising recruitment data, interviewing the trial management group and recruiters (n = 13), and audio-recording recruitment consultations (n = 64). Data were analysed using qualitative content and thematic analysis methods. In Phase II, strategies to improve recruitment were developed and delivered., Results: Initially many recruiters found it difficult to maintain a position of equipoise and held preconceptions about which treatment was best for particular patients. They did not feel comfortable about approaching all eligible patients, and when the study was discussed, biases were conveyed through the use of terminology, poorly balanced information, and direct treatment recommendations. Individual and group feedback led to presentations to patients becoming clearer and enabled recruiters to reconsider their sense of equipoise. Although the precise impact of the QRI alone cannot be determined, recruitment increased (from a mean [range] of 1.4 [0-4] to 4.5 [0-12] patients/month) and the feasibility study reached its recruitment target., Conclusion: Although clinicians find it challenging to recruit patients to a trial comparing different contemporary treatments for prostate cancer, training and support can enable recruiters to become more comfortable with conveying equipoise and providing clearer information to patients., (© 2018 The Authors BJU International published by John Wiley & Sons Ltd on behalf of BJU International.)

Context: Bladder cancer (BC) is a significant health problem, and understanding the risk factors for this disease could improve prevention and early detection., Objective: To provide a systematic review and summary of novel developments in epidemiology and risk factors for BC., Evidence Acquisition: A systematic review of original articles was performed by two pairs of reviewers (M.G.C., I.J., F.E., and K.P.) using PubMed/Medline in December 2017, updated in April 2018. To address our primary objective of reporting contemporary studies, we restricted our search to include studies from the last 5yr. We subdivided our review according to specific risk factors (PICO [Population Intervention Comparator Outcome])., Evidence Synthesis: Our search found 2191 articles, of which 279 full-text manuscripts were included. We separated our manuscripts by the specific risk factor they addressed (PICO). According to GLOBOCAN estimates, there were 430000 new BC cases and 165000 deaths worldwide in 2012. Tobacco smoking and occupational exposure to carcinogens remain the factors with the highest attributable risk. The literature was limited by heterogeneity of data., Conclusions: Evidence is emerging regarding gene-environment interactions, particularly for tobacco and occupational exposures. In some populations, incidence rates are declining, which may reflect a decrease in smoking. Standardisation of reporting may help improve epidemiologic evaluation of risk., Patient Summary: Bladder cancer is common worldwide, and the main risk factors are tobacco smoking and exposure to certain chemicals in the working and general environments. There is ongoing research to identify and reduce risk factors, as well as to understand the impact of genetics on bladder cancer risk., (Copyright © 2018. Published by Elsevier B.V.)

Objectives: To provide data on the prevalence of urinary, bowel and sexual dysfunction in Northern Ireland (NI), to act as a baseline for studies of prostate cancer outcomes and to aid service provision within the general population., Subjects and Methods: A cross-sectional postal survey of 10 000 men aged ≥40 years in NI was conducted and age-matched to the distribution of men living with prostate cancer. The EuroQoL five Dimensions five Levels (EQ-5D-5L) and 26-item Expanded Prostate Cancer Composite (EPIC-26) instruments were used to enable comparisons with prostate cancer outcome studies. Whilst representative of the prostate cancer survivor population, the age-distribution of the sample differs from the general population, thus data were generalised to the NI population by excluding those aged 40-59 years and applying survey weights. Results are presented as proportions reporting problems along with mean composite scores, with differences by respondent characteristics assessed using chi-squared tests, analysis of variance, and multivariable log-linear regression., Results: Amongst men aged ≥60 years, 32.8% reported sexual dysfunction, 9.3% urinary dysfunction, and 6.5% bowel dysfunction. In all, 38.1% reported at least one problem and 2.1% all three. Worse outcome was associated with increasing number of long-term conditions, low physical activity, and higher body mass index (BMI). Urinary incontinence, urinary irritation/obstruction, and sexual dysfunction increased with age; whilst urinary incontinence, bowel, and sexual dysfunction were more common among the unemployed., Conclusion: These data provide an insight into sensitive issues seldom reported by elderly men, which result in poor general health, but could be addressed given adequate service provision. The relationship between these problems, raised BMI and low physical activity offers the prospect of additional health gain by addressing public health issues such as obesity. The results provide essential contemporary population data against which outcomes for those living with prostate cancer can be compared. They will facilitate greater understanding of the true impact of specific treatments such as surgical interventions, pelvic radiation or androgen-deprivation therapy., (© 2018 The Authors BJU International published by John Wiley & Sons Ltd on behalf of BJU International.)

Context: High-grade T1 (T1HG) bladder cancer (BCa) has a very high likelihood of disease recurrence and progression to muscle invasion. Radical cystectomy is considered the best chance at cure, albeit with a high risk of morbidity, and is overtreatment for some patients. Treatment with bacillus Calmette-Guerin (BCG) allows bladder preservation but may risk disease progression., Objective: To systematically review the current literature on the management of T1HG BCa and provide updated treatment recommendations., Evidence Acquisition: Medline, EMBASE, and Epub Ahead of Print databases were searched in November 2017 to identify observational cohort studies and controlled trials, between 1946 and 2017, associated with diagnosis, treatment, and prognosis of T1HG BCa., Evidence Synthesis: Clinical understaging and/or persistence of disease is not uncommon at initial transurethral resection (TUR); thus, a second re-TUR is recommended for cases with T1HG BCa. Patients electing a bladder preservation approach should undergo induction BCG therapy followed by a maintenance schedule, while patients with several high-risk features should consider immediate cystectomy and those with BCG-refractory or BCG-unresponsive disease should be considered for early cystectomy. Current phase I/II clinical trials for T1HG patients may offer future bladder preservation therapy approaches., Conclusions: T1HG tumours are heterogeneous in nature and challenging to treat. Bladder preservation with BCG induction and maintenance, or radical cystectomy is the current standard treatment modality of choice for these tumours. Promising therapies for BCG-unresponsive disease are currently under investigation., Patient Summary: Patients with high-grade T1 bladder cancer are at a high risk of tumour recurrence and progression, requiring more aggressive treatment such as bladder removal. Bladder preservation therapies are available (and new therapies are being tested in clinical trials); however, patients should be aware that currently bladder removal is considered the best opportunity for cancer cure., (Copyright © 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Patient-reported outcome measures (PROMs) are important tools used to understand patient-focused outcomes from care. Various PROMs have been developed for patients with bladder cancer (BC), although the disease's heterogeneity makes selection difficult. Accurate measurement of health-related quality of life (HRQL) can only be achieved if the PROM chosen is 'fit for purpose' (i.e. psychometrically sound). Systematic reviews of psychometric properties are useful for selecting the best PROM for a specific purpose. The COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) developed a checklist to improve the selection of health measurement instruments as part of a review process. Our aims were to undertake a systematic review, using the COSMIN criteria, to assess the quality of studies that report the psychometric properties of PROMs used with people with BC and determine the psychometric quality of these PROMs. An electronic search of seven databases including PubMed, MEDLINE and EMBASE (PROSPERO reference CRD42016051974) was undertaken to identify English language publications, published between January 1990 and September 2017 that evaluated psychometric properties of PROMs used in BC research. Two researchers independently screened abstracts and selected full-text papers. Studies were rated on methodological quality using the COSMIN checklist. Overall, 4663 records were screened and 23 studies, reporting outcomes in 3568 patients, were evaluated using the COSMIN checklist. Most PROMs had limited information reported about their psychometric properties. Studies reporting on the Bladder Cancer Index (BCI) and Functional Assessment of Cancer Therapy Vanderbilt Cystectomy Index (FACT-VCI) provided the most detail and these PROMs could be evaluated on the most COSMIN properties. Based on the available evidence, no existing PROM stands out as the most appropriate to measure HRQL in BC populations. This is due to two factors; (i) the heterogeneity of BC and its treatments (ii) no PROM was evaluated on all COSMIN measurement properties due to a lack of validation studies. We suggest future evaluation of generic, cancer generic and BC-specific PROMs to better understand their application with BC populations and propose strategies to help clinicians and researchers., (© 2018 The Authors BJU International published by John Wiley & Sons Ltd on behalf of BJU International.)

Active surveillance (AS) represents a well-recognized management option for many patients with low- and very low-risk prostate cancer (PCa). AS aims to reduce overtreatment whilst ensuring curative treatment for those in whom it is needed, without losing the window of curability. While long-term series have confirmed the safety of AS in carefully selected patients, this has resulted in new clinical questions. Can the inclusion criteria be expanded? Is there a role for biomarkers and multiparametric magnetic resonance imaging at diagnosis or during AS? What is the optimal follow-up schedule as well as the most meaningful trigger for definitive treatment? These questions, together with increasingly adopted heterogeneous protocols in AS, have prompted the European Association of Urology to produce a position paper corroborated by a summary of the scientific background on AS., Patient Summary: Active surveillance (AS) is becoming a widely adopted strategy for patients affected by low-risk prostate cancer. While a formal systematic review on the topic will soon be available, the European Association of Urology has produced specific statements for different open questions on AS., (Copyright © 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: We examined a national data set to determine if workers employed in specific occupations develop distinct bladder cancer (BCa) phenotypes., Objective: To compare the incidence and disease-specific mortality (DSM) of localized and advanced BCa in workers with different job titles., Design, Setting, and Participants: BCa incidence, stage at diagnosis, and DSM in 1.7 million Finnish men (13 717 with BCa) and 1.7 million women (4282 with BCa) with annotated occupational descriptions. Follow-up was 37 and 43 million person-years, respectively., Outcome Measurements and Statistical Analysis: The gender-specific incidence and BCa DSM within each occupational category was compared with the expected number of cases based on the entire Finnish population to generate standardized incidence ratios (SIRs) and standard mortality ratios (SMRs)., Results and Limitations: Occupations were found that had significant differences in the incidence of localized (SIR loc ) and advanced (SIR adv , SMR adv ) BCa and DSM. Male chemical process workers (SIR loc /SIR adv : 5.19; 95% confidence interval [CI], 1.73-25.7), male military personnel (SIR loc /SIR adv : 6.4; 95% CI, 1.09-259.0), and male public safety workers (SIR loc /SIR adv : 1.77; 95% CI, 1.04-3.23) had significantly more localized than advanced tumors. In contrast, miscellaneous construction workers had more advanced than localized cancers for both genders (male SIR loc /SIR adv : 0.67; 95% CI, 0.53-0.86; female SIR loc /SIR adv : 0.12; 95% CI, 0.09-0.54). Male chemical process workers had fewer deaths from BCa than expected from advanced tumors (SMR adv : 0.32; 95% CI, 0.07-0.94), and miscellaneous constructions workers had more deaths from advanced tumors than expected (male SMR adv : 1.44; 95% CI, 1.10-1.85; female SMR adv : 3.35; 95% CI, 1.23-7.30). Limitations of this study are failure to control accurately for the effects of smoking and a lack of specific treatment information., Conclusions: Occupations exist that may differ in their risks for localized and advanced BCa and for DSM., Patient Summary: Occupations have been identified that may have different patterns of bladder cancer than expected. These findings may be explained by confounding factors such as exposure to tobacco smoke; however, it could be that workers with these job titles are exposed to specific bladder carcinogens., (Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Context: Management of bladder cancer (BC) is primarily driven by stage, grade, and biological potential. Knowledge of each is derived using clinical, histopathological, and radiological investigations. This multimodal approach reduces the risk of error from one particular test, but may present a staging dilemma when results conflict. Multiparametric magnetic resonance imaging (mpMRI) may improve patient care through imaging of the bladder with better resolution of the tissue planes than computed tomography and without radiation exposure., Objective: To define a standardized approach to imaging and reporting mpMRI for BC, by developing a VI-RADS score., Evidence Acquisition: We created VI-RADS (Vesical Imaging-Reporting And Data System) through consensus using existing literature., Evidence Synthesis: We describe standard imaging protocols and reporting criteria (including size, location, multiplicity, and morphology) for bladder mpMRI. We propose a five-point VI-RADS score, derived using T2-weighted MRI, diffusion-weighted imaging, and dynamic contrast enhancement, which suggests the risks of muscle invasion. We include sample images used to understand VI-RADS., Conclusions: We hope that VI-RADS will standardize reporting, facilitate comparisons between patients, and in future years, will be tested and refined if necessary. While we do not advocate mpMRI for all patients with BC, this imaging may compliment pathology or reduce radiation-based imaging. Bladder mpMRI may be most useful in patients with non-muscle-invasive cancers, in expediting radical treatment or for determining response to bladder-sparing approaches., Patient Summary: Magnetic resonance imaging (MRI) scans for bladder cancer are becoming more common and may provide accurate information that helps improve patient care. Here, we describe a standardized reporting criterion for bladder MRI. This should improve communication between doctors and allow better comparisons between patients., (Copyright © 2018 European Association of Urology. All rights reserved.)

Context: Perioperative and long-term functional and oncologic outcomes following radical cystectomy (RC) for localized bladder cancer remain unchanged despite advances in technique and perioperative management, as well as neoadjuvant and adjuvant therapy. Accurate assessment of a patient's perioperative risk is critical to inform preoperative counseling and determine a patient's fitness for RC., Objective: To review and synthesize conventional and novel objective patient-specific risk assessment tools that may be incorporated into clinical practice for perioperative risk prognostication with respect to both postoperative complications and long-term oncologic outcomes, patient counseling, and decision-making when RC is being considered., Evidence Acquisition: A collaborative review was performed to synthesize currently available evidence on comorbidity, age, body composition, nutrition, frailty, and geriatric assessments for patients undergoing RC., Evidence Synthesis: Current guidelines recommend that pre-RC risk assessment should take into account age, performance status, and comorbidity. However, conventional comorbidity indices perform inconsistently in accurate assessment of the risk of perioperative complications, prolonged rehabilitation, and long-term oncologic outcomes. Novel metrics including standardized assessments of dependency, comorbidity severity, sarcopenia, malnutrition, physical and cognitive frailty, and comprehensive geriatric assessments may offer more precise estimates of physiologic age and relative vulnerability to adverse outcomes following RC., Conclusions: Perioperative risk assessment before RC should incorporate objective measures of physiologic age, physical function, nutrition, lean muscularity, and frailty. The use of standardized multidimensional instruments should be encouraged for patients undergoing consideration for RC to identify potentially modifiable risk factors that can be targeted with prehabilitation interventions. Future work is needed to validate the performance of these metrics with respect to predicting perioperative complications and oncologic outcomes and to define and assess the effectiveness of specific prehabilitation interventions to optimize patients before surgery., Patient Summary: We review several metrics that doctors can use to measure the risks associated with bladder removal, a major surgical procedure. Moving beyond evaluating a patient's age, the burden of other health problems, and surgeon intuition, these tools may be used to counsel patients regarding their surgical risk, to predict oncologic outcomes, and to help identify potential interventions to improve surgical readiness., (Copyright © 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Introduction: Bladder cancer (BC) is a common malignancy and one of the most expensive to manage. Radical cystectomy (RC) with pelvic lymphadenectomy is a gold standard treatment for high-risk BC. Reductions in morbidity and mortality from RC may be achieved through robot-assisted RC (RARC). Prospective comparisons between open RC (ORC) and RARC have been limited by sample size, use of extracorporeal reconstruction and use of outcomes important for ORC. Conversely, while RARC is gaining in popularity, there is little evidence to suggest it is superior to ORC. We are undertaking a prospective randomised controlled trial (RCT) to compare RARC with intracorporeal reconstruction (iRARC) and ORC using multimodal outcomes to explore qualitative and quantitative recovery after surgery. METHODS AND ANALYSIS: iROC is a multicentre prospective RCT in English National Health Service (NHS) cancer centres. We will randomise 320 patients undergoing RC to either iRARC or ORC. Treatment allocation will occur after trial entry and consent. The primary outcome is days alive and out of hospital within the first 90 days from surgery. Secondary outcomes will measure functional recovery (activity trackers, chair-to-stand tests and health related quality of life (HRQOL) questionnaires), morbidity (complications and readmissions), cost-effectiveness (using EuroQol-5 Domain-5 levels (EQ-5D-5L) and unit costs) and surgeon fatigue. Patients will be analysed according to intention to treat. The primary outcome will be transformed and analysed using regression. All statistical assumptions will be investigated. Secondary outcomes will be analysed using appropriate regression methods. An internal feasibility study of the first 30 patients will evaluate recruitment rates, acceptance of randomised treatment choice, compliance outcome collection and to revise our sample size., Ethics and Dissemination: The study has ethical approval (REC reference 16/NE/0418). Findings will be made available to patients, clinicians, funders and the NHS through peer-reviewed publications, social media and patient support groups., Trial Registration Numbers: ISRCTN13680280 and NCT03049410., Competing Interests: Competing interests: Within iROC, robotic consumables are provider without cost from Intuitive Surgical. JMcG has received educational funding from Intuitive Surgical., (© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Context: Initial treatment for most bladder cancers (BCs) involves transurethral resection (TUR) or tumours. Often more cancer is found after the initial treatment in around half of patients, requiring a second resection. Repeat transurethral resection (reTUR) is recommended for high-risk, non-muscle-invasive bladder cancer (NMIBC) to remove any residual disease and improve cancer outcomes., Objective: To systematically review the practice and therapeutic benefit of an early reTUR for high-risk NMIBC., Evidence Acquisition: A systematic review of original articles was performed using PubMed/Medline and Web of Science databases in December 2016 (initial) and October 2017 (final). We searched the references of included papers., Evidence Synthesis: We screened 15 209 manuscripts and selected 31 detailing 8409 persons with high-grade Ta and T1BC for inclusion. Detrusor muscle was found at initial TUR histology in 30-100% of cases. Residual tumour at reTUR was found in 17-67% of patients following Ta and in 20-71% following T1 cancer. Most residual tumours (36-86%) were found at the original resection site. Upstaging occurred in 0-8% (Ta to ≥T1) and 0-32% (T1 to ≥T2) of cases. Conflicting data report the impact of reTUR on subsequent recurrence and cancer-specific mortality. Recurrence for Ta was 16% in the reTUR group versus 58% in the non-reTUR group. For T1, recurrence ranged from 18% to 56%, but no clear trend was identified between reTUR and control. No clear relationship between reTUR and progression was found for Ta, although for T1 rates were higher in the non-reTUR group in series with control populations (5/6 studies). Overall mortality was slightly reduced in the reTUR group in two studies with controls (22-30% vs 26-36% [no reTUR])., Conclusions: Residual tumour is common after TUR for high-risk NMIBC. The reTUR helps in the diagnosis of this residual cancer and may improve outcomes for cancers initially staged as T1., Patient Summary: Some bladder cancers (BCs) are aggressive but confined to the bladder surface. Initial treatment includes endoscopic resection. More cancer is found after the initial treatment in approximately half of patients. In the aggressive but confined group of BC, a second resection, a few weeks after the first, may help find this residual cancer and improve outcomes, although the evidence quality for this is weak., (Copyright © 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

The dissemination of cancer cells to local and distant sites depends on a complex and poorly understood interplay between malignant cells and the cellular and non-cellular components surrounding them, collectively termed the tumour microenvironment. One of the most abundant cell types of the tumour microenvironment is the fibroblast, which becomes corrupted by locally derived cues such as TGF-β1 and acquires an altered, heterogeneous phenotype (cancer-associated fibroblasts, CAF) supportive of tumour cell invasion and metastasis. Efforts to develop new treatments targeting the tumour mesenchyme are hampered by a poor understanding of the mechanisms underlying the development of CAF. Here, we examine the contribution of microRNA to the development of experimentally-derived CAF and correlate this with changes observed in CAF derived from tumours. Exposure of primary normal human fibroblasts to TGF-β1 resulted in the acquisition of a myofibroblastic CAF-like phenotype. This was associated with increased expression of miR-145, a miRNA predicted in silico to target multiple components of the TGF-β signalling pathway. miR-145 was also overexpressed in CAF derived from oral cancers. Overexpression of miR-145 blocked TGF-β1-induced myofibroblastic differentiation and reverted CAF towards a normal fibroblast phenotype. We conclude that miR-145 is a key regulator of the CAF phenotype, acting in a negative feedback loop to dampen acquisition of myofibroblastic traits, a key feature of CAF associated with poor disease outcome.

Background: Urothelial bladder cancer (UBC) accounts for 10,000 new diagnoses and 5000 deaths annually in the UK (Cancer Research UK, http://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/bladder-cancer , Cancer Research UK, Accessed 26 Mar 2018). Cisplatin-based chemotherapy is standard of care therapy for UBC for both palliative first-line treatment of advanced/metastatic disease and radical neoadjuvant treatment of localised muscle invasive bladder cancer. However, cisplatin resistance remains a critical cause of treatment failure and a barrier to therapeutic advance in UBC. Based on supportive pre-clinical data, we hypothesised that DNA methyltransferase inhibition would circumvent cisplatin resistance in UBC and potentially other cancers., Methods: The addition of SGI-110 (guadecitabine, a DNA methyltransferase inhibitor) to conventional doublet therapy of gemcitabine and cisplatin (GC) is being tested within the phase Ib/IIa SPIRE clinical trial. SPIRE incorporates an initial, modified rolling six-dose escalation phase Ib design of up to 36 patients with advanced solid tumours followed by a 20-patient open-label randomised controlled dose expansion phase IIa component as neoadjuvant treatment for UBC. Patients are being recruited from UK secondary care sites. The dose escalation phase will determine a recommended phase II dose (RP2D, primary endpoint) of SGI-110, by subcutaneous injection, on days 1-5 for combination with GC at conventional doses (cisplatin 70 mg/m 2 , IV infusion, day 8; gemcitabine 1000 mg/m 2 , IV infusion, days 8 and 15) in every 21-day cycle. In the dose expansion phase, patients will be randomised 1:1 to GC with or without SGI-110 at the proposed RP2D. Secondary endpoints will include toxicity profiles, SGI-110 pharmacokinetics and pharmacodynamic biomarkers, and pathological complete response rates in the dose expansion phase. Analyses will not be powered for formal statistical comparisons and descriptive statistics will be used to describe rates of toxicity, efficacy and translational endpoints by treatment arm., Discussion: SPIRE will provide evidence for whether SGI-110 in combination with GC chemotherapy is safe and biologically effective prior to future phase II/III trials as a neoadjuvant therapy for UBC and potentially in other cancers treated with GC., Trial Registration: EudraCT Number: 2015-004062-29 (entered Dec 7, 2015) ISRCTN registry number: 16332228 (registered on Feb 3, 2016).

Background: Multimodal enhanced recovery after surgery (ERAS) regimens have improved outcomes from colorectal surgery., Objective: We report the application of ERAS to patients undergoing radical cystectomy (RC)., Design, Setting, and Participants: Prospective collection of outcomes from consecutive patients undergoing RC at a single institution., Intervention: Twenty-six components including prehabilitation exercise, same day admission, carbohydrate fluid loading, targeted intraoperative fluid resuscitation, regional local anaesthesia, cessation of nasogastric tubes, omitting oral bowel preparation, avoiding drain use, early mobilisation, chewing gum use, and audit., Outcome Measurements and Statistical Analysis: Primary outcomes were length of stay and readmission rate. Secondary outcomes included intraoperative blood loss, transfusion rates, survival, and histopathological findings., Results and Limitations: Four hundred and fifty-three consecutive patients underwent RC, including 393 (87%) with ERAS. Length of stay was shorter with ERAS (median [interquartile range]: 8 [6-13] d) than without (18 [13-25], p<0.001). Patients with ERAS had lower blood loss (ERAS: 600 [383-969] ml vs 1050 [900-1575] ml for non-ERAS, p<0.001), lower transfusion rates (ERAS: 8.1% vs 25%, chi-square test, p<0.001), and fewer readmissions (ERAS: 15% vs 25%, chi-square test, p=0.04) than those without. Histopathological parameters (eg, tumour stage, node count, and margin state) and survival outcomes did not differ with ERAS use (all p>0.1). Multivariable analysis revealed ERAS use was (p=0.002) independently associated with length of stay., Conclusions: The use of ERAS pathways was associated with lower intraoperative blood loss and faster discharge for patients undergoing RC. These changes did not increase readmission rates or alter oncological outcomes., Patient Summary: Recovery after major bladder surgery can be improved by using enhanced recovery pathways. Patients managed by these pathways have shorter length of stays, lower blood loss, and lower transfusion rates. Their adoption should be encouraged., (Copyright © 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Introduction: High-risk non-muscle invasive bladder cancer (HRNMIBC) is a heterogeneous disease that can be difficult to predict. While around 25% of cancers progress to invasion and metastases, the remaining majority of tumours remain within the bladder. It is uncertain whether patients with HRNMIBC are better treated with intravesical maintenance BCG (mBCG) immunotherapy or primary radical cystectomy (RC). A definitive randomised controlled trial (RCT) is needed to compare these two different treatments but may be difficult to recruit to and has not been attempted to date. Before undertaking such an RCT, it is important to understand whether such a comparison is possible and how best to achieve it., Methods and Analysis: BRAVO is a multi-centre, parallel-group, mixed-methods, individually randomised, controlled, feasibility study for patients with HRNMIBC. Participants will be randomised to receive either mBCG immunotherapy or RC. The primary objective is to assess the feasibility and acceptability of performing the definitive phase III trial via estimation of eligibility and recruitment rates, assessing uptake of allocated treatment and compliance with mBCG, determining quality-of-life questionnaire completion rates and exploring reasons expressed by patients for declining recruitment into the study. We aim to recruit 60 participants from six centres in the UK. Surgical trials with disparate treatment options find recruitment challenging from both the patient and clinician perspective. By building on the experiences of other similar trials through implementing a comprehensive training package aimed at clinicians to address these challenges (qualitative substudy), we hope that we can demonstrate that a phase III trial is feasible., Ethics and Dissemination: The study has ethical approval (16/YH/0268). Findings will be made available to patients, clinicians, the funders and the National Health Service through traditional publishing and social media., Trial Registration Number: ISRCTN12509361; Pre results., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)