Hyperthermic intravesical chemotherapy with mitomycin-C for the treatment of high-risk non-muscle-invasive bladder cancer patients.

Objectives: The objectives of the study are to explore tolerability, acceptability and oncological outcomes for patients with high-risk non-muscle-invasive bladder cancer (NMIBC) treated with hyperthermic intravesical chemotherapy (HIVEC) and mitomycin-C (MMC) at our institution. Patients and Methods: Our single-institution, observational study consists of consecutive high-risk NMIBC patients treated with HIVEC and MMC. Our HIVEC protocol included six weekly instillations (induction), followed by two further cycles of three instillations (maintenance) (6 + 3 + 3) if there was cystoscopic response. Patient demographics, instillation dates and adverse events (AEs) were collected prospectively in our dedicated HIVEC clinic. Retrospective case-note review was performed to evaluate oncological outcomes. Primary outcomes were tolerability and acceptability of HIVEC protocol; secondary outcomes were 12-month recurrence-free, progression-free and overall survival. Results: In total, 57 patients (median age 80.3 years) received HIVEC and MMC, with a median follow-up of 18 months. Of these, 40 (70.2%) had recurrent tumours, and 29 (50.9%) had received prior Bacillus Calmette-Guérin (BCG). HIVEC induction was completed by 47 (82.5%) patients, but only 19 (33.3%) completed the full protocol. Disease recurrence (28.9%) and AEs (28.9%) were the most common reasons for incompletion of protocol; five (13.2%) patients stopped treatment due to logistical challenges. AEs occurred in 20 (35.1%) patients; the most frequently documented were rash (10.5%), urinary tract infection (8.8%) and bladder spasm (8.8%). Progression during treatment occurred in 11 (19.3%) patients, 4 (7.0%) of whom had muscle invasion and 5 (8.8%) subsequently required radical treatment. Patients who had received prior BCG were significantly more likely to progress (p = 0.04). 12-month recurrence-free, progression-free and overall survival rates were 67.5%, 82.2%, and 94.7%, respectively. Conclusions: Our single-institution experience suggests that HIVEC and MMC are tolerable and acceptable. Oncological outcomes in this predominantly elderly, pretreated cohort are promising; however, disease progression was higher in patients pretreated with BCG. Further randomised noninferiority trials comparing HIVEC versus BCG in high-risk NMIBC are required.

Oncological Outcomes for Patients Harboring Positive Surgical Margins Following Radical Cystectomy for Muscle-Invasive Bladder Cancer: A Retrospective Multicentric Study on Behalf of the YAU Urothelial Group.

Introduction: Adjuvant therapy has no defined role for patients with positive surgical margins (PSMs) following radical cystectomy (RC) for muscle-invasive bladder cancer (MIBC). The aim of our study was to describe loco-regional recurrence-free survival (LRFS), metastatic-free survival (MFS), recurrence-free survival (RFS), cancer-specific survival (CSS) and overall survival (OS) and identify predictors of each endpoint in patients with PSMs following RC for MIBC. Methods: A collaborative retrospective cohort study was conducted on 394 patients with PSMs who underwent RC for MIBC between January 2000 and December 2018 at 10 tertiary referral centers. Patients receiving perioperative radiotherapy were excluded from the study. Kaplan−Meier curves were used to estimate patient survival. Cox regression analysis was used to identify predictors of survival. Results: Median age at surgery was 70 years (IQR 62−76) with 129 (33%) and 204 (52%) patients had pT3 and pT4 tumors, respectively. Nodal metastasis (pN+) was identified in 148 (38%). Soft tissue PSMs were found in 283 (72%) patients, urethral PSMs in 65 (16.5%), and ureteral PSMs were found in 73 (18.5%). The median follow-up time was 44 months (95% CI 32−60). Median LRFS, MRFS, RFS, CSS, and OS were 14 (95% CI 11−17), 12 (95% CI 10−16), 10 (95% CI 8−12), 23 (95% CI 18−33), and 16 months (95% CI 12−19), respectively. On multivariable Cox regression analysis, the pT3−4 stage, pN+ stage, and multifocal PSMs were independent predictors of LRFS, MRFS, RFS, and OS. Adjuvant chemotherapy improved all oncological outcomes studied (p < 0.05). The number of lymph nodes removed was independently associated with better LRFS, MRFS, and RFS. Advanced age at diagnosis was independently associated with worse OS. Conclusion: Patients with PSMs following RC have poor outcomes since half of them will recur within a year and will die of their disease. Among all PSMs types, patients with multifocal PSMs harbor the worst prognosis. We observed a benefit of adjuvant chemotherapy, but clinical trials evaluating innovative adjuvant strategies for these patients remain an unmet need.

Effect of Robot-Assisted Radical Cystectomy With Intracorporeal Urinary Diversion vs Open Radical Cystectomy on 90-Day Morbidity and Mortality Among Patients With Bladder Cancer: A Randomized Clinical Trial.

Importance: Robot-assisted radical cystectomy is being performed with increasing frequency, but it is unclear whether total intracorporeal surgery improves recovery compared with open radical cystectomy for bladder cancer. Objectives: To compare recovery and morbidity after robot-assisted radical cystectomy with intracorporeal reconstruction vs open radical cystectomy. Design, Setting, and Participants: Randomized clinical trial of patients with nonmetastatic bladder cancer recruited at 9 sites in the UK, from March 2017-March 2020. Follow-up was conducted at 90 days, 6 months, and 12 months, with final follow-up on September 23, 2021. Interventions: Participants were randomized to receive robot-assisted radical cystectomy with intracorporeal reconstruction (n = 169) or open radical cystectomy (n = 169). Main Outcomes and Measures: The primary outcome was the number of days alive and out of the hospital within 90 days of surgery. There were 20 secondary outcomes, including complications, quality of life, disability, stamina, activity levels, and survival. Analyses were adjusted for the type of diversion and center. Results: Among 338 randomized participants, 317 underwent radical cystectomy (mean age, 69 years; 67 women [21%]; 107 [34%] received neoadjuvant chemotherapy; 282 [89%] underwent ileal conduit reconstruction); the primary outcome was analyzed in 305 (96%). The median number of days alive and out of the hospital within 90 days of surgery was 82 (IQR, 76-84) for patients undergoing robotic surgery vs 80 (IQR, 72-83) for open surgery (adjusted difference, 2.2 days [95% CI, 0.50-3.85]; P = .01). Thromboembolic complications (1.9% vs 8.3%; difference, -6.5% [95% CI, -11.4% to -1.4%]) and wound complications (5.6% vs 16.0%; difference, -11.7% [95% CI, -18.6% to -4.6%]) were less common with robotic surgery than open surgery. Participants undergoing open surgery reported worse quality of life vs robotic surgery at 5 weeks (difference in mean European Quality of Life 5-Dimension, 5-Level instrument scores, -0.07 [95% CI, -0.11 to -0.03]; P = .003) and greater disability at 5 weeks (difference in World Health Organization Disability Assessment Schedule 2.0 scores, 0.48 [95% CI, 0.15-0.73]; P = .003) and at 12 weeks (difference in WHODAS 2.0 scores, 0.38 [95% CI, 0.09-0.68]; P = .01); the differences were not significant after 12 weeks. There were no statistically significant differences in cancer recurrence (29/161 [18%] vs 25/156 [16%] after robotic and open surgery, respectively) and overall mortality (23/161 [14.3%] vs 23/156 [14.7%]), respectively) at median follow-up of 18.4 months (IQR, 12.8-21.1). Conclusions and Relevance: Among patients with nonmetastatic bladder cancer undergoing radical cystectomy, treatment with robot-assisted radical cystectomy with intracorporeal urinary diversion vs open radical cystectomy resulted in a statistically significant increase in days alive and out of the hospital over 90 days. However, the clinical importance of these findings remains uncertain. Trial Registration: ISRCTN Identifier: ISRCTN13680280; ClinicalTrials.gov Identifier: NCT03049410.

Impact of Anaesthetist Volume on Radical Cystectomy Outcomes.

BACKGROUND: Radical cystectomy (RC) is a gold standard treatment for aggressive bladder cancer. Higher surgical volumes through centralisation are associated with improved RC outcomes. The impact of anaesthetist experience and RC volume on outcomes is less clear. OBJECTIVE: We sought to examine RC outcomes stratified by anaesthetist volume using a contemporary homogenous series. DESIGN, SETTING, AND PARTICIPANTS: A retrospective analysis of a prospectively collected, single-surgeon database of RC patients over a 10-yr period. INTERVENTION: Four hundred and fifty-three consecutive patients underwent RC, including 430 (95%) with anaesthetist annotation. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Anaesthetists were stratified into low- (<10 cases) and high-volume (≥10 cases) classes. Primary outcomes were blood loss, transfusion rates, length of stay (LOS), and postoperative mortality. RESULTS AND LIMITATIONS: In total, 63 anaesthetists were included for analysis (median two RCs per anaesthetist). Of 63 anaesthetists, 56 (88.9%) and seven (11.1%) were classified, respectively, into low and high volume, and these provided cover for 110 (25.6%) and 320 (74.4%) patients, respectively. When comparing high- versus low-volume anaesthetists, there were shorter LOS (median [interquartile range {IQR}]: 10 [6-14] vs 12 [7-19] d, p = 0.008), lower blood loss (median [IQR]: 600 [384-1000] vs 800 [500-1275] ml, p<0.001), and lower transfusion rate (23/320, 7.2% vs 22/110, 20%; p < 0.001). There was no difference in disease-specific mortality, overall mortality, or readmission rates. In multivariable analysis, a high anaesthetist volume was independently associated with transfusion rate (odds ratio 0.24 [0.07-0.83], p = 0.02). CONCLUSIONS: Higher-volume anaesthetists have lower transfusion rates for RC patients. Whilst LOS and blood loss may also differ with experience, there is no difference in mortality after RC. PATIENT SUMMARY: Radical cystectomy is a major operation. Experienced anaesthetists give fewer blood products to patients undergoing this operation. They may also help reduce blood loss and speed recovery. However, all other recovery measures were similar.

The Impact of Centralised Services on Metric Reflecting High-quality Performance: Outcomes from 1110 Consecutive Radical Cystectomies at a Single Centre.

BACKGROUND: The 2002 National Institute for Health and Care Excellence guidance on centralisation of radical cystectomy (RC) coincided with changes in practice: use of neoadjuvant chemotherapy (NAC) and pelvic lymph node dissection (PLND), and RC for high-risk non-muscle-invasive bladder cancer (HR-NMIBC). OBJECTIVE: To report the outcomes of RC at a single centre and to compare trends in survival with respect to centralisation and change in RC practice. DESIGN, SETTING, AND PARTICIPANTS: Data were collected retrospectively between 1 January 1994 and 31 December 2016. Patients with urothelial cell carcinoma (UCC) were selected. Outcomes from 1994 to 2007 (before centralisation, era 1) were compared with those from 2008 to 2016 (after centralisation, era 2). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was disease-specific mortality. Secondary outcomes were survival and use of NAC and PLND. RESULTS AND LIMITATIONS: Overall, 1100 RCs (era 1, 316; era 2, 794) were performed for UCC. Median (interquartile range [IQR]) follow-up was 28.5 (11.9-57.4) mo. RC for NMIBC was 36.2% versus 51.3% (p<0.001), NAC use was 2.2% versus 31.6% (p<0.001), and PLND use was 59.7% versus 76.4% (p<0.001) in era 1 versus era 2. The 30-d (1.6% [era 1] vs 0.8% [era 2], p=0.21) and 90-d (4.1% vs 2.6%, p=0.2) mortality rates did not differ with respect to RC year. Five-year disease-specific survival (DSS) was 56.0% in era 1 versus 79.0% in era 2 (p<0.001). RC for patients aged ≥75 yr was 13.9% versus 28.1% (p<0.001) and 30-d mortality in this group was 4.5% versus 0% (p=0.001) in era 1 versus era 2. The study is limited by its retrospective design. CONCLUSIONS: Centralisation was associated with higher rates of NAC and PLND use, and increased RC performed for older patients and patients with HR-NMIBC. DSS was higher and RC appeared to be safer for older patients (fewer postoperative mortalities) after centralisation. PATIENT SUMMARY: We looked at outcomes from bladder removal for bladder cancer. Survival outcomes improved following centralisation of services. Surgery appeared to be safer for older patients, as there were fewer postoperative mortalities after centralisation. Centralisation of radical cystectomy (RC) services was associated with higher rates of neoadjuvant chemotherapy and pelvic lymph node dissection use, and increased usage of RC for older patients with high-risk non-muscle-invasive bladder cancer. Survival outcomes from RC were superior after centralisation and safer for older patients undergoing RC (fewer postoperative mortalities).

Radical Cystectomy Against Intravesical BCG for High-Risk High-Grade Nonmuscle Invasive Bladder Cancer: Results From the Randomized Controlled BRAVO-Feasibility Study.

PURPOSE: High-grade nonmuscle invasive bladder cancer (HRNMIBC) is a heterogeneous disease. Treatments include intravesical maintenance Bacillus Calmette-Guerin (mBCG) and radical cystectomy (RC). We wanted to understand whether a randomized trial comparing these options was possible. MATERIALS AND METHODS: We conducted a two-arm, prospective multicenter randomized study to determine the feasibility in Bacillus Calmette-Guerin-naive patients. Participants had new high-risk HRNMIBC suitable for both treatments. Random assignment was stratified by age, sex, center, stage, presence of carcinoma in situ, and prior low-risk bladder cancer. Qualitative work investigated how to maintain equipoise. The primary outcome was the number of patients screened, eligible, recruited, and randomly assigned. RESULTS: We screened 407 patients, approached 185, and obtained consent from 51 (27.6%) patients. Of these, one did not proceed and therefore 50 were randomly assigned (1:1). In the mBCG arm, 23/25 (92.0%) patients received mBCG, four had nonmuscle invasive bladder cancer (NMIBC) after induction, three had NMIBC at 4 months, and four received RC. At closure, two patients had metastatic BC. In the RC arm, 20 (80.0%) participants received cystectomy, including five (25.0%) with no tumor, 13 (65.0%) with HRNMIBC, and two (10.0%) with muscle invasion in their specimen. At follow-up, all patients in the RC arm were free of disease. Adverse events were mostly mild and equally distributed (15/23 [65.2%] patients with mBCG and 13/20 [65.0%] patients with RC). The quality of life (QOL) of both arms was broadly similar at 12 months. CONCLUSION: A randomized controlled trial comparing mBCG and RC will be challenging to recruit into. Around 10% of patients with high-risk HRNMIBC have a lethal disease and may be better treated by primary radical treatment. Conversely, many are suitable for bladder preservation and may maintain their prediagnosis QOL.

Occupational bladder cancer: A cross section survey of previous employments, tasks and exposures matched to cancer phenotypes.

OBJECTIVES: Up to 10% of Bladder Cancers may arise following occupational exposure to carcinogens. We hypothesised that different cancer phenotypes reflected different patterns of occupational exposure. METHODS: Consecutive participants, with bladder cancer, self-completed a structured questionnaire detailing employment, tasks, exposures, smoking, lifestyle and family history. Our primary outcome was association between cancer phenotype and occupational details. RESULTS: We collected questionnaires from 536 patients, of whom 454 (85%) participants (352 men and 102 women) were included. Women were less likely to be smokers (68% vs. 81% Chi sq. p<0.001), but more likely than men to inhale environmental tobacco smoke at home (82% vs. 74% p = 0.08) and use hair dye (56% vs. 3%, p<0.001). Contact with potential carcinogens occurred in 282 (62%) participants (mean 3.1 per worker (range 0-14)). High-grade cancer was more common than low-grade disease in workers from the steel, foundry, metal, engineering and transport industries (p<0.05), and in workers exposed to crack detection dyes, chromium, coal/oil/gas by-products, diesel fumes/fuel/aircraft fuel and solvents (such as trichloroethylene). Higher staged cancers were frequent in workers exposed to Chromium, coal products and diesel exhaust fumes/fuel (p<0.05). Various workers (e.g. exposed to diesel fuels or fumes (Cox, HR 1.97 (95% CI 1.31-2.98) p = 0.001), employed in a garage (HR 2.19 (95% CI 1.31-3.63) p = 0.001), undertaking plumbing/gas fitting/ventilation (HR 2.15 (95% CI 1.15-4.01) p = 0.017), undertaking welding (HR 1.85 (95% CI 1.24-2.77) p = 0.003) and exposed to welding materials (HR 1.92 (95% CI 1.27-2.91) p = 0.002)) were more likely to have disease progression and receive radical treatment than others. Fewer than expected deaths were seen in healthcare workers (HR 0.17 (95% CI 0.04-0.70) p = 0.014). CONCLUSIONS: We identified multiple occupational tasks and contacts associated with bladder cancer. There were some associations with phenotype, although our study design precludes robust assessment.

The association of cigarette smoking and pathological response to neoadjuvant platinum-based chemotherapy in patients undergoing treatment for urinary bladder cancer - A prospective European multicenter observational study of the EAU Young Academic Urologists (YAU) urothelial carcinoma working group.

OBJECTIVE: To prospectively study the impact of smoking on pathological response to neoadjuvant chemotherapy (NAC) in patients undergoing radical cystectomy (RC) for urothelial carcinoma of the bladder (UCB). MATERIALS & METHODS: We collected standard clinicopathological variables, including smoking status (never, former, current) in patients undergoing NAC and RC for UCB at 12 European tertiary care centers between 12/2013-12/2015. Clinicopathological variables were compared according to smoking status. Multivariable logistic regression models were built to assess the association of smoking status and a) complete (no residual disease), b) partial (residual, non-muscle invasive disease), c) no pathological response (residual muscle invasive or lymph node positive disease). Kaplan-Meier and Cox regression analyses were employed to study the impact of response to NAC on survival. RESULTS AND LIMITATIONS: Our final cohort consisted of 167 NAC patients with a median follow-up of 15 months (interquartile range (IQR) 9-26 months) of whom 48 (29%), 69 (41%), and 50 (30%) where never, former, and current smokers, respectively. Smoking was significantly associated with advanced age (p = 0.013), worse ECOG performance status (p = 0.049), and decreased pathological response to NAC (p = 0.045). On multivariable logistic regression analyses, former and current smoking status was significantly associated with lower odds of complete pathological response (odds ratio (OR) 0.37, 95% confidence interval (CI) 0.16-0.87, p = 0.023, and OR 0.34, 95% CI 0.13-0.85, p = 0.021), while current smoking status was significantly associated with a greater likelihood of no pathological response (OR 2.49, 95% CI 1.02-6.06, p = 0.045). Response to NAC was confirmed as powerful predictor of survival. CONCLUSIONS: Smoking status is adversely associated with pathological response to NAC. Smokers should be informed about these adverse effects, counseled regarding smoking cessation, and possibly be considered for immunotherpeutics as they may be more effective in smokers.

Postoperative Chemotherapy Bladder Instillation After Radical Nephroureterectomy: Results of a European Survey from the Young Academic Urologist Urothelial Cancer Group.

BACKGROUND: Level 1 evidence supports the administration of single postoperative intravesical chemotherapy (pIVC) following radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC), in order to decrease intravesical recurrence risk. OBJECTIVE: The Young Academic Urologist Urothelial Cancer Group aimed to investigate the use of pIVC in daily practice among European colleagues. DESIGN SETTING AND PARTICIPANTS: An online survey was shared with European Association of Urology Section of Oncological Urology (ESOU) 2017 participants via e-mail. Submissions were accepted from April to June 2017. The topics for 15 questions of this survey included the habit of delivering pIVC, the choice of drug, its dosage, related doubts or concerns, reasons not to perform pIVC, knowledge of the evidence, and surgical preferences for RNU. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Survey software was used for analyses. Logistic regression analyses were used to investigate the association between surgeons' experience and caseloads with pIVC utilization. RESULTS AND LIMITATIONS: Overall, 127 responses were collected (11.6%). About half of the participants (47%) regularly administered pIVC following RNU. The drug most commonly utilized was mitomycin (85%); 82% adhered to the standard dosage of 40 mg. Different administration protocols were adopted: ≤48 h (39%), 7-10 postoperative days (35%), >10 d (11%), and intraoperatively (10%). The evidence was supported by prospective randomized clinical trials for only 65% of responders. Among interviewees who did not deliver pIVC, the most commonly reported reasons were lack of supporting data (55%), fear of potential side effects (18%), and organizational hurdles (15%). CONCLUSIONS: Our research highlights the limited use of pIVC following RNU for UTUC, raising the question of how the compliance with level 1 evidence in the urological community may be promoted. PATIENT SUMMARY: Level 1 evidence supports the administration of single postoperative intravesical chemotherapy (pIVC) following radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC), in order to decrease intravesical recurrence risk. The Young Academic Urologist Urothelial Cancer Group aimed to investigate the use of pIVC in daily practice among European colleagues. Our research highlights the limited use of pIVC (47%) following RNU for UTUC, raising the question of how the compliance with level 1 evidence in the urological community may be promoted.

Urothelial Carcinoma in Bladder Diverticula: A Multicenter Analysis of Characteristics and Clinical Outcomes.

BACKGROUND: Urothelial carcinoma arising in a bladder diverticulum (UCBD) is uncommon, and data on treatment and outcome are sparse. OBJECTIVE: To analyze clinicopathological characteristics of UCBD and to compare outcome after radical cystectomy (RC) and partial cystectomy (PC). DESIGN, SETTING, AND PARTICIPANTS: Data of 115 UCBD patients treated with RC (n=81) or PC (n=34) between 2000 and 2016 were collected from 11 institutional databases and were analyzed retrospectively. Median follow-up was 5.0yr (95% confidence interval [CI]: 4.0-6.2). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Upstaging of tumor stage at diagnostic transurethral resection (TUR) to the RC/PC specimen was investigated. Overall survival (OS) and metastasis-free survival (MFS) after RC and PC were analyzed using Kaplan-Meier estimates, and compared using the log-rank test. Intravesical recurrences after PC were reported. A multivariable Cox proportional-hazard model was used to identify factors associated with OS. RESULTS AND LIMITATIONS: There were no statistically significant differences in clinicopathological characteristics between RC and PC groups. Fifty-five percent of patients with cTa/is/1 at diagnostic TUR had ≥pT2 tumors at RC/PC. Five-year OS and MFS were, respectively, 62% and 66% for RC and 66% and 55% for PC (p=0.9 and p=0.6). Intravesical tumor recurrence was seen in six of 34 (18%) PC patients. In multivariable analysis, positive surgical margins and extravesical disease (≥pT2) were associated with worse OS, whereas treatment modality was not (RC: reference; PC: hazard ratio 0.94, [95% CI: 0.47-1.90], p=0.9). CONCLUSIONS: Upstaging of UCBD was frequent, indicating an inaccuracy in clinical staging. We found no differences in OS or MFS between PC and RC groups; therefore, PC may represent a feasible surgical alternative to RC in selected UCBD patients. PATIENT SUMMARY: In this report, we looked at the treatment of urothelial carcinoma arising in a bladder diverticulum (UCBD). We found that bladder-sparing treatment by partial cystectomy may be an alternative to radical cystectomy in carefully selected UCBD patients.

Epidemiology, aetiology and screening of bladder cancer.

Bladder cancer (BC) is a common, significant and expensive health condition. Understanding the risk factors for this disease is paramount to improving disease prevention and increasing public awareness. Historically BC has been a disease of industrialized regions and the most responsible carcinogens are tobacco smoke and occupational chemical exposure. BC incidence and mortality differ dramatically by region and reflect differences in risk factor exposure, healthcare behaviour, and population demographics. Screening studies have suggested a survival benefit amongst screened non-symptomatic populations with known risk factors, but this has not become standard practice.

Selection of patients and benefit of immediate radical cystectomy for non-muscle invasive bladder cancer.

Bladder cancer (BC) is a common disease in both sexes and majority of cases present as non-muscle invasive BC (NMIBC). The percentage of NMIBC progressing to muscle invasive BC (MIBC) varies between 25% and 75% and currently there are no reliable molecular markers that may predict the outcome of high-risk (HR) NMIBC. Transurethral resection of the bladder tumour (TURBT) with intravesical bacillus Calmette-Guérin (BCG) or immediate radical cystectomy (RC) are the current gold standard treatment options. The European Association of Urology (EAU) guidelines recommend immediate or delayed RC for HR- and a subgroup of "highest-risk" NMIBC. These cases include pT1, carcinoma in-situ (CIS), multifocal disease, histological variants such as micropapillary and sarcomatoid, and patients who have contraindications to, or have failed with BCG. The comparative risks between maintenance BCG (mBCG) and immediate RC are unclear. However, RC may give patients the best oncological outcome.

Discrepancy Between European Association of Urology Guidelines and Daily Practice in the Management of Non-muscle-invasive Bladder Cancer: Results of a European Survey.

BACKGROUND: The European Association of Urology (EAU) non-muscle-invasive bladder cancer (NMIBC) guidelines are meant to help minimise morbidity and improve the care of patients with NMIBC. However, there may be underuse of guideline-recommended care in this potentially curable cohort. OBJECTIVE: To assess European physicians' current practice in the management of NMIBC and evaluate its concordance with the EAU 2013 guidelines. DESIGN, SETTING, AND PARTICIPANTS: Initial 45-min telephone interviews were conducted with 20 urologists to develop a 26-item questionnaire for a 30-min online quantitative interview. A total of 498 physicians with predefined experience in treatment of NMIBC patients, from nine European countries, completed the online interviews. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Descriptive statistics of absolute numbers and percentages of the use of diagnostic tools, risk group stratification, treatment options chosen, and follow-up regimens were used. RESULTS AND LIMITATIONS: Guidelines are used by ≥87% of physicians, with the EAU guidelines being the most used ones (71-100%). Cystoscopy (60-97%) and ultrasonography (42-95%) are the most used diagnostic techniques. Using EAU risk classification, 40-69% and 88-100% of physicians correctly identify all the prognostic factors for low- and high-risk tumours, respectively. Re-transurethral resection of the bladder tumour (re-TURB) is performed in 25-75% of low-risk and 55-98% of high-risk patients. Between 21% and 88% of patients received a single instillation of chemotherapy within 24h after TURB. Adjuvant intravesical treatment is not given to 6-62%, 2-33%, and 1-20% of the patients with low-, intermediate-, and high-risk NMIBC, respectively. Patients with low-risk NMIBC are likely to be overmonitored and those with high-risk NMIBC undermonitored. Our study is limited by the possible recall bias of the selected physicians. CONCLUSIONS: Although most European physicians claim to apply the EAU guidelines, adherence to them is low in daily practice. PATIENT SUMMARY: Our survey among European physicians investigated discrepancies between guidelines and daily practice in the management of non-muscle-invasive bladder cancer (NMIBC). We conclude that the use of the recommended diagnostic tools, risk-stratification of NMIBC, and performance of re-TURB have been adopted, but adjuvant intravesical treatment and follow-up are not uniformly applied.

Long-term Outcomes from Re-resection for High-risk Non-muscle-invasive Bladder Cancer: A Potential to Rationalize Use.

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.

Occupation and Bladder Cancer Phenotype: Identification of Workplace Patterns That Increase the Risk of Advanced Disease Beyond Overall Incidence.

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 (SIRloc) and advanced (SIRadv, SMRadv) BCa and DSM. Male chemical process workers (SIRloc/SIRadv: 5.19; 95% confidence interval [CI], 1.73-25.7), male military personnel (SIRloc/SIRadv: 6.4; 95% CI, 1.09-259.0), and male public safety workers (SIRloc/SIRadv: 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 SIRloc/SIRadv: 0.67; 95% CI, 0.53-0.86; female SIRloc/SIRadv: 0.12; 95% CI, 0.09-0.54). Male chemical process workers had fewer deaths from BCa than expected from advanced tumors (SMRadv: 0.32; 95% CI, 0.07-0.94), and miscellaneous constructions workers had more deaths from advanced tumors than expected (male SMRadv: 1.44; 95% CI, 1.10-1.85; female SMRadv: 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.

Prospective Implementation of Enhanced Recovery After Surgery Protocols to Radical Cystectomy.

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.