Is a Single Nephrographic Phase Computed Tomography Sufficient for Detecting Urothelial Carcinoma in Patients with Visible Haematuria? A Prospective Paired Noninferiority Comparison.

Background: There is uncertainty about the utility of multiphase computed tomography (CT) compared with single-phase CT in the routine examination of patients with visible haematuria (VH). Objective: To compare the accuracies of single nephrographic phase (NP) CT and four-phase CT in detecting urothelial carcinoma (UC). Design setting and participants: This was a single-centre, prospective, paired, noninferiority study of patients with painless VH referred for CT before cystoscopy between September 2019 and June 2021. Patients were followed up for 1 yr to ascertain UC diagnosis. Intervention: All patients underwent four-phase CT (control), from which single NP CT (experimental) was extracted. Both were independently assessed for UC. Outcome measurements and statistical analysis: The primary outcome was the difference in accuracy between the control and experimental CT using a 7.5% noninferiority limit. Histologically verified UC defined a positive reference standard. Secondary outcomes included differences in sensitivity, specificity, negative (NPV) and positive (PPV) predictive values, and area under the curve (AUC). All results are reported per patient. Results and limitations: Of the 308 patients included, UC was diagnosed in 45 (14.6%). The difference in accuracy between the control and experimental CT was 1.9% (95% confidence interval -2.8 to 6.7), demonstrating noninferiority. Sensitivity was 93.3% versus 91.1%, specificity was 83.7% versus 81.8%, NPV was 98.7% versus 98.2%, PPV was 49.4% versus 46.1%, and AUC was 0.96 versus 0.94 for the control versus experimental CT. Limitations included a low number of UC cases and no definite criteria for selecting a noninferiority limit. Conclusions: The accuracy of NP CT is not inferior to that of four-phase CT for detecting UC. Patient summary: This study shows that a computed tomography (CT) examination with only one contrast phase is no worse than a more complex CT examination for detecting cancer in the urinary tract among patients presenting with visible blood in the urine.

The 2021 Updated European Association of Urology Guidelines on Metastatic Urothelial Carcinoma.

CONTEXT: Treatment of metastatic urothelial carcinoma is currently undergoing a rapid evolution. OBJECTIVE: This overview presents the updated European Association of Urology (EAU) guidelines for metastatic urothelial carcinoma. EVIDENCE ACQUISITION: A comprehensive scoping exercise covering the topic of metastatic urothelial carcinoma is performed annually by the Guidelines Panel. Databases covered by the search included Medline, EMBASE, and the Cochrane Libraries, resulting in yearly guideline updates. EVIDENCE SYNTHESIS: Platinum-based chemotherapy is the recommended first-line standard therapy for all patients fit to receive either cisplatin or carboplatin. Patients positive for programmed death ligand 1 (PD-L1) and ineligible for cisplatin may receive immunotherapy (atezolizumab or pembrolizumab). In case of nonprogressive disease on platinum-based chemotherapy, subsequent maintenance immunotherapy (avelumab) is recommended. For patients without maintenance therapy, the recommended second-line regimen is immunotherapy (pembrolizumab). Later-line treatment has undergone recent advances: the antibody-drug conjugate enfortumab vedotin demonstrated improved overall survival and the fibroblast growth factor receptor (FGFR) inhibitor erdafitinib appears active in case of FGFR3 alterations. CONCLUSIONS: This 2021 update of the EAU guideline provides detailed and contemporary information on the treatment of metastatic urothelial carcinoma for incorporation into clinical practice. PATIENT SUMMARY: In recent years, several new treatment options have been introduced for patients with metastatic urothelial cancer (including bladder cancer and cancer of the upper urinary tract and urethra). These include immunotherapy and targeted treatments. This updated guideline informs clinicians and patients about optimal tailoring of treatment of affected patients.

European Association of Urology Guidelines on Muscle-invasive and Metastatic Bladder Cancer: Summary of the 2020 Guidelines.

CONTEXT: This overview presents the updated European Association of Urology (EAU) guidelines for muscle-invasive and metastatic bladder cancer (MMIBC). OBJECTIVE: To provide practical evidence-based recommendations and consensus statements on the clinical management of MMIBC with a focus on diagnosis and treatment. EVIDENCE ACQUISITION: A broad and comprehensive scoping exercise covering all areas of the MMIBC guideline has been performed annually since its 2017 publication (based on the 2016 guideline). Databases covered by the search included Medline, EMBASE, and the Cochrane Libraries, resulting in yearly guideline updates. A level of evidence and a grade of recommendation were assigned. Additionally, the results of a collaborative multistakeholder consensus project on advanced bladder cancer (BC) have been incorporated in the 2020 guidelines, addressing those areas where it is unlikely that prospective comparative studies will be conducted. EVIDENCE SYNTHESIS: Variant histologies are increasingly reported in invasive BC and are relevant for treatment and prognosis. Staging is preferably done with (enhanced) computerised tomography scanning. Treatment decisions are still largely based on clinical factors. Radical cystectomy (RC) with lymph node dissection remains the recommended treatment in highest-risk non-muscle-invasive and muscle-invasive nonmetastatic BC, preceded by cisplatin-based neoadjuvant chemotherapy (NAC) for invasive tumours in "fit" patients. Selected men and women benefit from sexuality sparing RC, although this is not recommended as standard therapy. Open and robotic RC show comparable outcomes, provided the procedure is performed in experienced centres. For open RC 10, the minimum selected case load is 10 procedures per year. If bladder preservation is considered, chemoradiation is an alternative in well-selected patients without carcinoma in situ and after maximal resection. Adjuvant chemotherapy should be considered if no NAC was given. Perioperative immunotherapy can be offered in clinical trial setting. For fit metastatic patients, cisplatin-based chemotherapy remains the first choice. In cisplatin-ineligible patients, immunotherapy in Programmed Death Ligand 1 (PD-L1)-positive patients or carboplatin in PD-L1-negative patients is recommended. For second-line treatment in metastatic disease, pembrolizumab is recommended. Postchemotherapy surgery may prolong survival in responders. Quality of life should be monitored in all phases of treatment and follow-up. The extended version of the guidelines is available at the EAU website: https://uroweb.org/guideline/bladder-cancer-muscle-invasive-and-metastatic/. CONCLUSIONS: This summary of the 2020 EAU MMIBC guideline provides updated information on the diagnosis and treatment of MMIBC for incorporation into clinical practice. PATIENT SUMMARY: The European Association of Urology Muscle-invasive and Metastatic Bladder Cancer (MMIBC) Panel has released an updated version of their guideline, which contains information on histology, staging, prognostic factors, and treatment of MMIBC. The recommendations are based on the current literature (until the end of 2019), with emphasis on high-level data from randomised clinical trials and meta-analyses and on the findings of an international consensus meeting. Surgical removal of the bladder and bladder preservation are discussed, as well as the use of chemotherapy and immunotherapy in localised and metastatic disease.

European Association of Urology Guidelines on Upper Urinary Tract Urothelial Carcinoma: 2020 Update.

CONTEXT: The European Association of Urology (EAU) Guidelines Panel on Upper Urinary Tract Urothelial Carcinoma (UTUC) has prepared updated guidelines to aid clinicians in the current evidence-based management of UTUC and to incorporate recommendations into clinical practice. OBJECTIVE: To provide an overview of the EAU guidelines on UTUC as an aid to clinicians. EVIDENCE ACQUISITION: The recommendations provided in the current guidelines are based on a thorough review of available UTUC guidelines and articles identified following a systematic search of Medline. Data on urothelial malignancies and UTUC were searched using the following keywords: urinary tract cancer, urothelial carcinomas, upper urinary tract carcinoma, renal pelvis, ureter, bladder cancer, chemotherapy, ureteroscopy, nephroureterectomy, neoplasm, adjuvant treatment, instillation, recurrence, risk factors, and survival. References were weighted by a panel of experts. EVIDENCE SYNTHESIS: Owing to the rarity of UTUC, there are insufficient data to provide strong recommendations. The 2017 tumour, node, metastasis (TNM) classification is recommended. Recommendations are given for diagnosis and risk stratification as well as for radical and conservative treatment, and prognostic factors are discussed. A single postoperative dose of intravesical mitomycin after nephroureterectomy reduces the risk of bladder tumour recurrence. Kidney-sparing management should be offered as a primary treatment option to patients with low-risk tumour and two functional kidneys. After radical nephroureterectomy, cisplatin-based chemotherapy is indicated in locally advanced UTUC. CONCLUSIONS: These guidelines contain information on the management of individual patients according to a current standardised approach. Urologists should take into account the specific clinical characteristics of each patient when determining the optimal treatment regimen, based on the proposed risk stratification of these tumours. PATIENT SUMMARY: Urothelial carcinoma of the upper urinary tract is rare, but because 60% of these tumours are invasive at diagnosis, an appropriate diagnosis is most important. A number of known risk factors exist.

European Association of Urology Guidelines on Primary Urethral Carcinoma-2020 Update.

CONTEXT: Primary urethral carcinoma (PUC) is a rare cancer accounting for <1% of all genitourinary malignancies. OBJECTIVE: To provide updated practical recommendations for the diagnosis and management of PUC. EVIDENCE ACQUISITION: A systematic search interrogating Ovid (Medline), EMBASE, and the Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews was performed. EVIDENCE SYNTHESIS: Urothelial carcinoma of the urethra is the predominant histological type of PUC (54-65%), followed by squamous cell carcinoma (16-22%) and adenocarcinoma (10-16%). Diagnosis of PUC depends on urethrocystoscopy with biopsy and urinary cytology. Pathological staging and grading are based on the tumour, node, metastasis (TNM) classification and the 2016 World Health Organization grading systems. Local tumour extent and regional lymph nodes are assessed by magnetic resonance imaging, and the presence of distant metastases is assessed by computed tomography of the thorax/abdomen and pelvis. For all patients with localised distal tumours (≤T2N0M0), partial urethrectomy or urethra-sparing surgery is a valid treatment option, provided that negative intraoperative surgical margins can be achieved. Prostatic Ta-Tis-T1 PUC can be treated with repeat transurethral resection of the prostate and bacillus Calmette-Guérin. In prostatic or proximal ≥ T2N0 disease, neoadjuvant cisplatin-based chemotherapy should be considered prior to radical surgery. All patients with locally advanced disease (≥T3N0-2M0) should be discussed within a multidisciplinary team. In men with locally advanced squamous cell carcinoma, curative radiotherapy combined with radiosensitising chemotherapy can be offered for definitive treatment and genital preservation. In patients with local urethral recurrence, salvage surgery or radiotherapy can be offered. For patients with distant metastatic disease, systemic therapy based on tumour characteristics can be evaluated. CONCLUSIONS: These updated European Association of Urology guidelines provide up-to-date guidance for the contemporary diagnosis and management of patients with suspected PUC. PATIENT SUMMARY: Primary urethral carcinoma (PUC) is a very rare, but aggressive disease. These updated European Association of Urology guidelines provide evidence-based guidance for clinicians treating patients with PUC.

The Importance of Hospital and Surgeon Volume as Major Determinants of Morbidity and Mortality After Radical Cystectomy for Bladder Cancer: A Systematic Review and Recommendations by the European Association of Urology Muscle-invasive and Metastatic Bladder Cancer Guideline Panel.

CONTEXT: In bladder cancer patients treated with radical cystectomy (RC), controversy exists regarding the impact of the annual hospital volume (HV) and/or surgeon volume (SV) on oncological outcomes and quality of care. OBJECTIVE: A systematic review was performed to evaluate the impact of HV and SV on clinical outcomes. Primary outcomes included in-hospital, 30-d, and 90-d mortality. Secondary outcomes included complications, long-term survival, positive surgical margin rate, lymphadenectomy performance, length of hospital stay, neobladder performance, and blood loss/transfusion rate. EVIDENCE ACQUISITION: Medline, Embase, and the Cochrane Central Register of Controlled Trials were searched. Comparative studies published after the year of 2000 including patients who underwent RC for bladder cancer were eligible for inclusion. Partial cystectomy was an exclusion criterion. Risk of bias (RoB) assessment was performed according to the ROBINS-1 tool. EVIDENCE SYNTHESIS: After screening of 1190 abstracts, 39 studies recruiting 549 542 patients were included. All studies were retrospective observation cohort studies (level of evidence 3). Twenty-two studies reported on HV only, six studies on SV only, and 12 on both. Higher HV, specifically an HV of >10, was associated with improved primary and secondary outcomes in most studies. In addition, there is some evidence that an HV of >20 improves outcomes. For SV, limited and conflicting data are reported. Most studies had moderate to high RoB. The results were synthesized narratively. CONCLUSIONS: Acknowledging the lower level of evidence, HV is likely associated with in-hospital, 30- and 90-d mortality, as well as the secondary outcomes assessed. Based on this study, the European Association of Urology Muscle-invasive and Metastatic Bladder Cancer Guideline Panel recommends hospitals to perform at least 10, and preferably >20, RCs annually or refer the patient to a center that reaches this number. For SV, limited and conflicting data are available. The available evidence suggests HV rather than SV to be the main driver of perioperative outcomes. PATIENT SUMMARY: Current literature suggests that the number of bladder removal operations per hospital per year is associated with postoperative survival as well as the quality of care provided.

European Association of Urology Guidelines on Upper Urinary Tract Urothelial Carcinoma: 2017 Update.

CONTEXT: The European Association of Urology (EAU) Guidelines Panel on Upper Urinary Tract Urothelial Carcinoma (UTUC) has prepared updated guidelines to aid clinicians in the current evidence-based management of UTUC and to incorporate recommendations into clinical practice. OBJECTIVE: To provide an overview of the EAU guidelines on UTUC as an aid to clinicians. EVIDENCE ACQUISITION: The recommendations provided in the current guidelines are based on a thorough review of available UTUC guidelines and articles identified following a systematic search of Medline. Data on urothelial malignancies and UTUC were searched using the following keywords: urinary tract cancer; urothelial carcinomas; upper urinary tract, carcinoma; renal pelvis; ureter; bladder cancer; chemotherapy; ureteroscopy; nephroureterectomy; adjuvant treatment; instillation; recurrence; risk factors; and survival. References were weighted by a panel of experts. EVIDENCE SYNTHESIS: Owing to the rarity of UTUC, there are insufficient data to provide strong recommendations (ie, grade A). However, the results of recent multicentre studies are now available, and there is a growing number of retrospective articles in UTUC. The 2017 tumour, node, metastasis (TNM) classification is recommended. Recommendations are given for diagnosis and risk stratification, as well as for radical and conservative treatment; prognostic factors are also discussed. A single postoperative dose of intravesical mitomycin after radical nephroureterectomy reduces the risk of bladder tumour recurrence. Kidney-sparing management should be offered as a primary treatment option to patients with low-risk tumours and two functional kidneys. CONCLUSIONS: These guidelines contain information on the management of individual patients according to a current standardised approach. Urologists should take into account the specific clinical characteristics of each patient when determining the optimal treatment regimen, based on the proposed risk stratification of these tumours. PATIENT SUMMARY: Urothelial carcinoma of the upper urinary tract is rare, but because 60% of these tumours are invasive at diagnosis; appropriate diagnosis and management is most important. We present recommendations based on current evidence for optimal management.

Oncological and functional outcomes of sexual function-preserving cystectomy compared with standard radical cystectomy in men: A systematic review.

INTRODUCTION: Different sexual function-preserving surgical techniques aimed at improving voiding and sexual function in patients undergoing radical cystectomy for bladder cancer have been described. The objective of this systematic review is to determine the effect of sexual function-preserving cystectomy (SPC) on functional and oncological outcomes. MATERIALS AND METHODS: Relevant databases were searched covering the time frame 2000 to 2015. All publications presenting data on any type of SPC reporting oncological or functional outcomes with a minimum follow-up of 1 year were identified. Comparative studies including a minimum of 30 patients and single-arm case series with a minimum of 50 patients were selected. No language restrictions were applied. RESULTS: In a total of 8,517 identified abstracts, 12 studies were eligible for inclusion. SPC described included prostate-, capsule-, seminal vesicle, and nerve-sparing techniques. Local recurrence ranged from 1.2% to 61.1% (vs. 16.0%-55.0% in the control group) and metastatic disease from 0% to 33.3% (vs. 33.0%). No differences were found in comparative studies reporting oncological outcomes. Postoperative potency was significantly better in the SPC groups in 6 studies comparing sexual function-preserving cystectomy vs. radical cystectomy (P<0.05). No major effect on continence was found. Overall, there was moderate to high risk of bias and confounding. CONCLUSIONS: The evidence base for prostate-, capsule-, or nerve-sparing cystectomy suggests that these procedures may yield better sexual outcomes than standard cystectomy, without compromising oncological outcomes. However, the overall quality of the evidence was moderate, and hence if offered, patients must be carefully selected, counseled, and closely monitored.

Systematic review of the oncological and functional outcomes of pelvic organ-preserving radical cystectomy (RC) compared with standard RC in women who undergo curative surgery and orthotopic neobladder substitution for bladder cancer.

CONTEXT: Pelvic organ-preserving radical cystectomy (POPRC) for women may improve postoperative sexual and urinary functions without compromising the oncological outcome compared with standard radical cystectomy (RC). OBJECTIVE: To determine the effect of POPRC on sexual, oncological and urinary outcomes compared with RC in women who undergo standard curative surgery and orthotopic neobladder substitution for bladder cancer. EVIDENCE ACQUISITION: Medline, Embase, Cochrane controlled trials databases and clinicaltrial.gov were systematically searched for all relevant publications. Women with bladder cancer who underwent POPRC or standard RC and orthotopic neobladder substitution with curative intent were included. Prospective and retrospective comparative studies and single-arm case series were included. The primary outcomes were sexual function at 6-12 months after surgery and oncological outcomes including disease recurrence and overall survival (OS) at >2 years. Secondary outcomes included urinary continence at 6-12 months. Risk of bias (RoB) assessment was performed using standard Cochrane review methodology including additional domains based on confounder assessment. EVIDENCE SYNTHESIS: The searches yielded 11 941 discrete articles, of which 15 articles reporting on 15 studies recruiting a total of 874 patients were eligible for inclusion. Three papers had a matched-pair study design and the rest of the studies were mainly small, retrospective case series. Sexual outcomes were reported in seven studies with 167/194 patients (86%) having resumed sexual activity within 6 months postoperatively, with median (range) patients' sexual satisfaction score of 88.5 (80-100)%. Survival outcomes were reported in seven studies on 197 patients, with a mean follow-up of between 12 and 132 months. At 3 and 5 years, cancer-specific survival was 70-100% and OS was 65-100%. In all, 11 studies reported continence outcomes. Overall, the daytime and night-time continence rates were 58-100% and 42-100%, respectively. Overall, the self-catheterisation rate was 9.5-78%. Due to poor reporting and large heterogeneity between studies, instead of subgroup-analysis, a narrative synthesis approach was used. The overall RoB was high across all studies. CONCLUSION: For well-selected patients, POPRC with orthotopic neobladder may potentially be comparable to standard RC for oncological outcomes, whilst improving sexual and urinary function outcomes. However, in women undergoing RC, oncological and functional data regarding POPRC remain immature and require further evaluation in a prospective comparative setting.

Updated 2016 EAU Guidelines on Muscle-invasive and Metastatic Bladder Cancer.

CONTEXT: Invasive bladder cancer is a frequently occurring disease with a high mortality rate despite optimal treatment. The European Association of Urology (EAU) Muscle-invasive and Metastatic Bladder Cancer (MIBC) Guidelines are updated yearly and provides information to optimise diagnosis, treatment, and follow-up of this patient population. OBJECTIVE: To provide a summary of the EAU guidelines for physicians and patients confronted with muscle-invasive and metastatic bladder cancer. EVIDENCE ACQUISITION: An international multidisciplinary panel of bladder cancer experts reviewed and discussed the results of a comprehensive literature search of several databases covering all sections of the guidelines. The panel defined levels of evidence and grades of recommendation according to an established classification system. EVIDENCE SYNTHESIS: Epidemiology and aetiology of bladder cancer are discussed. The proper diagnostic pathway, including demands for pathology and imaging, is outlined. Several treatment options, including bladder-sparing treatments and combinations of treatment modalities (different forms of surgery, radiation therapy, and chemotherapy) are described. Sequencing of these modalities is discussed. Potential indications and contraindications, such as comorbidity, are related to treatment choice. There is a new paragraph on organ-sparing approaches, both in men and in women, and on minimal invasive surgery. Recommendations for chemotherapy in fit and unfit patients are provided including second-line options. Finally, a follow-up schedule is provided. CONCLUSIONS: The current summary of the EAU Muscle-invasive and Metastatic Bladder Cancer Guidelines provides an up-to-date overview of the available literature and evidence dealing with diagnosis, treatment, and follow-up of patients with metastatic and muscle-invasive bladder cancer. PATIENT SUMMARY: Bladder cancer is an important disease with a high mortality rate. These updated guidelines help clinicians refine the diagnosis and select the appropriate therapy and follow-up for patients with metastatic and muscle-invasive bladder cancer.

Oncologic Outcomes of Kidney-sparing Surgery Versus Radical Nephroureterectomy for Upper Tract Urothelial Carcinoma: A Systematic Review by the EAU Non-muscle Invasive Bladder Cancer Guidelines Panel.

CONTEXT: There is uncertainty regarding the oncologic effectiveness of kidney-sparing surgery (KSS) compared with radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). OBJECTIVE: To systematically review the current literature comparing oncologic outcomes of KSS versus RNU for UTUC. EVIDENCE ACQUISITION: A computerised bibliographic search of the Medline, Embase, and Cochrane databases was performed for all studies reporting comparative oncologic outcomes of KSS versus RNU. Approaches considered for KSS were segmental ureterectomy (SU) and ureteroscopic (URS) or percutaneous (PC) management. Using the methodology recommended by the Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines, we identified 22 nonrandomised comparative retrospective studies published between 1999 and 2015 that were eligible for inclusion in this systematic review. A narrative review and risk-of-bias (RoB) assessment were performed using cancer-specific survival (CSS) as the primary end point. EVIDENCE SYNTHESIS: Seven studies compared KSS overall (n=547) versus RNU (n=1376). Information on the comparison of SU (n=586) versus RNU (n=3692), URS (n=162) versus RNU (n=367), and PC (n=66) versus RNU (n=114) was available in 10, 5, and 2 studies, respectively. No significant difference was found between SU and RNU in terms of CSS or any other oncologic outcomes. Only patients with low-grade and noninvasive tumours experienced similar CSS after URS or PC when compared with RNU, despite an increased risk of local recurrence following endoscopic management of UTUC. The RoB assessment revealed, however, that the analyses were subject to a selection bias favouring KSS. CONCLUSIONS: Our systematic review suggests similar survival after KSS versus RNU only for low-grade and noninvasive UTUC when using URS or PC. However, selected patients with high-grade and invasive UTUC could safely benefit from SU when feasible. These results should be interpreted with caution due to the risk of selection bias. PATIENT SUMMARY: We reviewed the studies that compared kidney-sparing surgery versus radical nephroureterectomy for upper tract urothelial carcinoma. We found similar oncologic outcomes for favourable tumours when using ureteroscopic or percutaneous management, whereas indications for segmental ureterectomy could be extended to selected cases of aggressive tumours.

European Association of Urology Guidelines on Upper Urinary Tract Urothelial Cell Carcinoma: 2015 Update.

CONTEXT: The European Association of Urology (EAU) guidelines panel on upper urinary tract urothelial cell carcinoma (UTUC) has prepared updated guidelines to aid clinicians in the current evidence-based management of UTUC and to incorporate recommendations into clinical practice. OBJECTIVE: To provide a brief overview of the EAU guidelines on UTUC as an aid to clinicians. EVIDENCE ACQUISITION: The recommendations provided in the current guidelines are based on a thorough review of available UTUC guidelines and articles identified following a systematic search of Medline. Data on urothelial malignancies and UTUC were searched using these keywords: urinary tract cancer; urothelial carcinomas; upper urinary tract, carcinoma; renal pelvis; ureter; bladder cancer; chemotherapy; nephroureterectomy; adjuvant treatment; instillation; neoadjuvant treatment; recurrence; risk factors; and survival. References were weighted by a panel of experts. EVIDENCE SYNTHESIS: Due to the rarity of UTUC, there are insufficient data to provide strong recommendations (ie, grade A). However, the results of recent multicentre studies are now available, and there is a growing interest in UTUC. The 2009 TNM classification is recommended. Recommendations are given for diagnosis and risk stratification as well as radical and conservative treatment, and prognostic factors are discussed. A single postoperative dose of intravesical mitomycin after nephroureterectomy reduces the risk of bladder tumour recurrence. Recommendations are also provided for patient follow-up after different therapeutic strategies. CONCLUSIONS: These guidelines contain information on the management of individual patients according to a current standardised approach. Urologists should take into account the specific clinical characteristics of each patient when determining the optimal treatment regimen, based on the proposed risk stratification of these tumours. PATIENT SUMMARY: Urothelial carcinoma of the upper urinary tract is rare, but because 60% of these tumours are invasive at diagnosis, an appropriate diagnosis is most important. A number of known risk factors exist.

The impact of the extent of lymphadenectomy on oncologic outcomes in patients undergoing radical cystectomy for bladder cancer: a systematic review.

CONTEXT: Controversy exists regarding the therapeutic value of lymphadenectomy (LND) in patients undergoing radical cystectomy (RC) for muscle-invasive bladder cancer (MIBC). OBJECTIVE: To systematically review the relevant literature assessing the impact of LND on oncologic and perioperative outcomes in patients undergoing RC for MIBC. EVIDENCE ACQUISITION: Medline, Medline In-Process, Embase, the Cochrane Central Register of Controlled Trials, and the Latin American and Caribbean Center on Health Sciences Information (LILACS) were searched up to December 2013. Comparative studies reporting on no LND, limited LND (L-LND), standard LND (S-LND), extended LND (E-LND), superextended LND (SE-LND), and oncologic and perioperative outcomes were included. Risk-of-bias and confounding assessments were performed. EVIDENCE SYNTHESIS: Twenty-three studies reporting on 19,793 patients were included. All but one study were retrospective. Planned meta-analyses were not possible because of study heterogeneity; therefore, data were synthesized narratively. There were high risks of bias and confounding across most studies as well as extreme heterogeneity in the definition of the anatomic boundaries of LND templates. All seven studies comparing LND with no LND favored LND in terms of better oncologic outcomes. Seven of 14 studies comparing (super)extended LND with L-LND or S-LND reported a beneficial outcome for (super)extended LND in at least a subset of patients. No difference in outcome was reported in two studies comparing E-LND and S-LND. The comparative harms of different extents of LND remain unclear. CONCLUSIONS: Although the quality of the data was poor, the available evidence indicates that any kind of LND is advantageous over no LND. Similarly, E-LND appears to be superior to lesser degrees of dissection, while SE-LND offered no additional benefits. It is hoped that data from ongoing randomized clinical trials will clarify remaining uncertainties. PATIENT SUMMARY: The current literature suggests that removal of lymph nodes in bladder cancer surgery is beneficial and might result in better outcomes in terms of prolonging survival; however, the quality of the available studies is poor, and high-quality studies are needed.

EAU guidelines on muscle-invasive and metastatic bladder cancer: summary of the 2013 guidelines.

CONTEXT: The European Association of Urology (EAU) guidelines panel on Muscle-invasive and Metastatic bladder cancer (BCa) updates its guidelines yearly. This updated summary provides a synthesis of the 2013 guidelines document, with emphasis on the latest developments. OBJECTIVE: To provide graded recommendations on the diagnosis and treatment of patients with muscle-invasive BCa (MIBC), linked to a level of evidence. EVIDENCE ACQUISITION: For each section of the guidelines, comprehensive literature searches covering the past 10 yr in several databases were conducted, scanned, reviewed, and discussed both within the panel and with external experts. The final results are reflected in the recommendations provided. EVIDENCE SYNTHESIS: Smoking and work-related carcinogens remain the most important risk factors for BCa. Computed tomography (CT) and magnetic resonance imaging can be used for staging, although CT is preferred for pulmonary evaluation. Open radical cystectomy with an extended lymph node dissection (LND) remains the treatment of choice for treatment failures in non-MIBC and T2-T4aN0M0 BCa. For well-informed, well-selected, and compliant patients, however, multimodality treatment could be offered as an alternative, especially if cystectomy is not an option. Comorbidity, not age, should be used when deciding on radical cystectomy. Patients should be encouraged to actively participate in the decision-making process, and a continent urinary diversion should be offered to all patients unless there are specific contraindications. For fit patients, cisplatinum-based neoadjuvant chemotherapy should always be discussed, since it improves overall survival. For patients with metastatic disease, cisplatin-containing combination chemotherapy is recommended. For unfit patients, carboplatin combination chemotherapy or single agents can be used. CONCLUSIONS: This 2013 EAU Muscle-invasive and Metastatic BCa guidelines updated summary aims to increase the quality of care and outcome for patients with muscle-invasive or metastatic BCa. PATIENT SUMMARY: In this paper we update the EAU guidelines on Muscle-invasive and Metastatic bladder cancer. We recommend that chemotherapy be administered before radical treatment and that bladder removal be the standard of care for disease confined to the bladder.

EAU guidelines on primary urethral carcinoma.

CONTEXT: The European Association of Urology (EAU) Guidelines Group on Muscle-Invasive and Metastatic Bladder Cancer prepared these guidelines to deliver current evidence-based information on the diagnosis and treatment of patients with primary urethral carcinoma (UC). OBJECTIVE: To review the current literature on the diagnosis and treatment of patients with primary UC and assess its level of scientific evidence. EVIDENCE ACQUISITION: A systematic literature search was performed to identify studies reporting urethral malignancies. Medline was searched using the controlled vocabulary of the Medical Subject Headings database, along with a free-text protocol. EVIDENCE SYNTHESIS: Primary UC is considered a rare cancer, accounting for <1% of all malignancies. Risk factors for survival include age, tumour stage and grade, nodal stage, presence of distant metastasis, histologic type, tumour size, tumour location, and modality of treatment. Pelvic magnetic resonance imaging is the preferred method to assess the local extent of urethral tumour; computed tomography of the thorax and abdomen should be used to assess distant metastasis. In localised anterior UC, urethra-sparing surgery is an alternative to primary urethrectomy in both sexes, provided negative surgical margins can be achieved. Patients with locally advanced UC should be discussed by a multidisciplinary team of urologists, radiation oncologists, and oncologists. Patients with noninvasive UC or carcinoma in situ of the prostatic urethra and prostatic ducts can be treated with a urethra-sparing approach with transurethral resection and bacillus Calmette-Guérin (BCG). Cystoprostatectomy with extended pelvic lymphadenectomy should be reserved for patients not responding to BCG or as a primary treatment option in patients with extensive ductal or stromal involvement. CONCLUSIONS: The 2013 guidelines document on primary UC is the first publication on this topic by the EAU. It aims to increase awareness in the urologic community and provide scientific transparency to improve outcomes of this rare urogenital malignancy.

CT urography for hematuria.

Hematuria can signify serious disease such as bladder cancer, upper urinary tract urothelial cell carcinoma (UUT-UCC), renal cell cancer or urinary tract stones. CT urography is a rapidly evolving technique made possible by recent advances in CT technology. CT urography is defined as CT examination of the kidneys, ureters and bladder with at least one series of images acquired during the excretory phase after intravenous contrast administration. The reasoning for using CT urography to investigate hematuria is based on its high diagnostic accuracy for urothelial cell carcinoma (UCC) and favorable comparison with other imaging techniques. The optimum diagnostic imaging strategy for patients with hematuria at high-risk for UCC involves the use of CT urography as a replacement for other imaging tests (ultrasonography, intravenous urography, or retrograde ureteropyelography) and as a triage test for cystoscopy, resulting in earlier diagnosis and improved prognosis of bladder cancer, UUT-UCC, renal cell cancer and stones. Current problems with CT urography for investigating hematuria might be solved with a formative educational program simulating clinical reporting to reduce reader error, and a new technique for image-guided biopsy of UUT-UCC detected by CT urography for histopathological confirmation of diagnosis and elimination of false-positive results. CT urography is recommended as the initial imaging test for hematuria in patients at high-risk for UCC.

Evaluation of diagnostic strategies for bladder cancer using computed tomography (CT) urography, flexible cystoscopy and voided urine cytology: results for 778 patients from a hospital haematuria clinic.

UNLABELLED: Study Type - Diagnostic (exploratory cohort) Level of Evidence 2b What's known on the subject? and What does the study add? Haematuria clinics with same day imaging and flexible cystoscopy are an efficient way for investigating patients with haematuria. The principal role of haematuria clinics with reference to bladder cancer is to determine which patients are 'normal' and may be discharged, and which patients are abnormal and should undergo rigid cystoscopy. It is well recognised that CT urography offers a thorough evaluation of the upper urinary tract for stones, renal masses and urothelial neoplasms but the role of CT urography for diagnosing bladder cancer is less certain. The aim of the present study was to evaluate the diagnostic accuracy of CT urography in patients with visible haematuria aged >40 years and to determine if CT urography has a role for diagnosing bladder cancer. This study shows that the optimum diagnostic strategy for investigating patients with visible haematuria aged >40 years with infection excluded is a combined strategy using CT urography and flexible cystoscopy. Patients positive for bladder cancer on CT urography should be referred directly for rigid cystoscopy and so avoid flexible cystoscopy. The number of flexible cystoscopies required therefore may be reduced by 17%. The present study also shows that the diagnostic accuracy of voided urine cytology is too low to justify its continuing use in a haematuria clinic using CT urography and flexible cystoscopy. OBJECTIVES: To evaluate and compare the diagnostic accuracy of computed tomography (CT) urography with flexible cystoscopy and voided urine cytology for diagnosing bladder cancer. To evaluate diagnostic strategies using CT urography as: (i) an additional test or (ii) a replacement test or (iii) a triage test for diagnosing bladder cancer in patients referred to a hospital haematuria rapid diagnosis clinic. PATIENTS AND METHODS: The clinical cohort consisted of a consecutive series of 778 patients referred to a hospital haematuria rapid diagnosis clinic from 1 March 2004 to 17 December 2007. Criteria for referral were at least one episode of macroscopic haematuria, age >40 years and urinary tract infection excluded. Of the 778 patients, there were 747 with technically adequate CT urography and flexible cystoscopy examinations for analysis. On the same day, patients underwent examination by a clinical nurse specialist followed by voided urine cytology, CT urography and flexible cystoscopy. Voided urine cytology was scored using a 5-point system. CT urography was reported immediately by a uroradiologist and flexible cystoscopy performed by a urologist. Both examinations were scored using a 3-point system: 1, normal; 2, equivocal; and 3, positive for bladder cancer. The reference standard consisted of review of the hospital imaging and histopathology databases in December 2009 for all patients and reports from the medical notes for those referred for rigid cystoscopy. Follow-up was for 21-66 months. RESULTS: The prevalence of bladder cancer in the clinical cohort was 20% (156/778). For the diagnostic strategy using CT urography as an additional test for diagnosing bladder cancer, when scores of 1 were classified as negative and scores of 2 and 3 as positive, sensitivity was 1.0 (95% confidence interval [CI] 0.98-1.00), specificity was 0.94 (95% CI 0.91-0.95), the positive predictive value (PPV) was 0.80 (95% CI 0.73-0.85) and the negative predictive value (NPV) was 1.0 (95% CI 0.99-1.00). For the diagnostic strategy using CT urography as a replacement test for flexible cystoscopy for diagnosing bladder cancer, when scores of 1 were classified as negative and scores of 2 and 3 as positive, sensitivity was 0.95 (95% CI 0.90-0.97), specificity was 0.83 (95% CI 0.80-0.86), the PPV was 0.58 (95% CI 0.52-0.64), and the NPV was 0.98 (95% CI 0.97-0.99). Similarly using flexible cystoscopy for diagnosing bladder cancer, if scores of 1 were classified as negative and scores of 2 and 3 as positive, sensitivity was 0.98 (95% CI 0.94- 0.99), specificity was 0.94 (95% CI 0.92-0.96), the PPV was 0.80 (95% CI 0.73-0.85) and the NPV was 0.99 (95% CI 0.99-1.0). For the diagnostic strategy using CT urography and flexible cystoscopy as a triage test for rigid cystoscopy and follow-up (option 1), patients with a positive CT urography score are referred directly for rigid cystoscopy, and patients with an equivocal or normal score were referred for flexible cystoscopy. Sensitivity was 1.0 (95% CI 0.98-1.0), specificity was 0.94 (95% CI 0.91-0.95), the PPV was 0.80 (95% CI 0.73-0.85), and the NPV was 1.0 (95% CI 0.99-1.0). For the diagnostic strategy using CT urography and flexible cystoscopy as a triage test for rigid cystoscopy and follow-up (option 2), patients with a positive CT urography score are referred directly for rigid cystoscopy, patients with an equivocal score are referred for flexible cystoscopy and patients with a normal score undergo clinical follow-up. Sensitivity was 0.95 (95% CI 0.90-0.97), specificity was 0.98 (95% CI 0.97-0.99), the PPV was 0.93 (95% CI 0.87-0.96), and the NPV was 0.99 (95% CI 0.97-0.99). For voided urine cytology, if scores of 0-3 were classified as negative and 4-5 as positive for bladder cancer, sensitivity was 0.38 (95% CI 0.31-0.45), specificity was 0.98 (95% CI 0.97-0.99), the PPV was 0.82 (95% CI 0.72-0.88) and the NPV was 0.84 (95% CI 0.81-0.87). CONCLUSIONS: There is a clear advantage for the diagnostic strategy using CT urography and flexible cystoscopy as a triage test for rigid cystoscopy and follow-up (option 1), in which patients with a positive CT urography score for bladder cancer are directly referred for rigid cystoscopy, but all other patients undergo flexible cystoscopy. Diagnostic accuracy is the same as for the additional test strategy with the advantage of a 17% reduction of the number of flexible cystoscopies performed. The sensitivity of voided urine cytology is too low to justify its continuing use in a hospital haematuria rapid diagnosis clinic using CT urography and flexible cystoscopy.

Treatment of muscle-invasive and metastatic bladder cancer: update of the EAU guidelines.

CONTEXT: New data regarding treatment of muscle-invasive and metastatic bladder cancer (MiM-BC) has emerged and led to an update of the European Association of Urology (EAU) guidelines for MiM-BC. OBJECTIVE: To review the new EAU guidelines for MiM-BC with a specific focus on treatment. EVIDENCE ACQUISITION: New literature published since the last update of the EAU guidelines in 2008 was obtained from Medline, the Cochrane Database of Systematic Reviews, and reference lists in publications and review articles and comprehensively screened by a group of urologists, oncologists, and a radiologist appointed by the EAU Guidelines Office. Previous recommendations based on the older literature on this subject were also taken into account. Levels of evidence (LEs) and grades of recommendations (GRs) were added based on a system modified from the Oxford Centre for Evidence-based Medicine Levels of Evidence. EVIDENCE SYNTHESIS: Current data demonstrate that neoadjuvant chemotherapy in conjunction with radical cystectomy (RC) is recommended in certain constellations of MiM-BC. RC remains the basic treatment of choice in localised invasive disease for both sexes. An attempt has been made to define the extent of surgery under standard conditions in both sexes. An orthotopic bladder substitute should be offered to both male and female patients lacking any contraindications, such as no tumour at the level of urethral dissection. In contrast to neoadjuvant chemotherapy, current advice recommends the use of adjuvant chemotherapy only within clinical trials. Multimodality bladder-preserving treatment in localised disease is currently regarded only as an alternative in selected, well-informed, and compliant patients for whom cystectomy is not considered for medical or personal reasons. In metastatic disease, the first-line treatment for patients fit enough to sustain cisplatin remains cisplatin-containing combination chemotherapy. With the advent of vinflunine, second-line chemotherapy has become available. CONCLUSIONS: In the treatment of localised invasive bladder cancer (BCa), the standard treatment remains radical surgical removal of the bladder within standard limits, including as-yet-unspecified regional lymph nodes. However, the addition of neoadjuvant chemotherapy must be considered for certain specific patient groups. A new drug for second-line chemotherapy (vinflunine) in metastatic disease has been approved and is recommended.