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Objective: To evaluate whether differences exist between men and women in response to intravesical BCG treatments. The incidence of urothelial carcinoma of the bladder is lower in women but they tend to present with more aggressive and advanced disease. Some prior studies also suggest there are sex-based differences in response to treatment for non-muscle invasive bladder tumors., Methods: In this retrospective study, we reviewed all consecutive patients who received BCG at the CHU de Québec - Laval University from 2009-2019. Men and women were treated with intravesical BCG therapy following pathologic confirmation of urothelial carcinoma. Outcomes evaluated include recurrence, progression, and treatment tolerability. Recurrence was defined as a pathology confirmed cancer whereas progression was the new development of high-grade (recurrence) pathology or an increase of stage. Tolerability was defined according to the proportion of prescribed BCG received. All clinical details were obtained through review of the medical records, collaborated by pharmacy records for BCG administration. Competing-risk analysis was used to compare outcomes., Results: Among 613 patients who received BCG at our institution between 2009-2019, 472 (77.0%) were men and 141 (23.0%) were women. The recurrence rate was not different between sexes, with a 5-year recurrence risk of 52% (95% CI: 36.93-65.4) among women compared to 57.5% (CI 95%: 51.9-62.6) among men. The overall non-progression rate at 1,3 and 5 years was 97.3% (95% CI: 95.6%-98.3%), 93.6% (95% CI: 91.2%-95.4%), and 91.7% (95% CI: 88.4%-94.1%), respectively. The completion of ≥5 induction BCG instillations and maintenance BCG use was similar in both genders., Conclusions: We report a contemporary NMIBC cohort treated with BCG and find no clear evidence for sex-based differences in response to BCG treatment in regard of progression, recurrence, and tolerability., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Context: Bladder cancer demonstrates striking gender-based differences in incidence, with a role for androgens possibly implicated in the development and progression of the disease. Emerging preclinical and clinical evidence suggests that there may be a role for antiandrogen therapy in bladder cancer., Objective: This systematic review assessed the current clinical evidence evaluating androgen suppressive therapy (AST) for the treatment or prevention of bladder cancer., Evidence Acquisition: Following Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines, MEDLINE was searched for full-text articles detailing clinical outcomes or incidence of bladder cancer among patients who received AST, defined as gonadotropin-releasing hormone agonists or equivalent, androgen receptor antagonists, or 5-alpha reductase inhibitors., Evidence Synthesis: A total of 12 studies were included. Five studies focused on prostate cancer patients, with one study in men with lower urinary tract symptoms. Among these studies, a lower incidence of bladder cancer was observed in five, with adjusted risk reduction estimates ranging from 7% to 47%. Six studies evaluating 11 820 bladder cancer patients investigated clinical outcomes among men who received a form of AST. Three out of four studies evaluating recurrence-free survival found a benefit for AST, with adjusted hazard ratios for recurrence of non-muscle-invasive cancer ranging from 0.29 to 0.53. Limitations included large variability in data sources and methodologies, as well as no data on tolerability., Conclusions: Current evidence indicates that antiandrogen therapies exert a favorable influence on bladder tumors. Further prospective studies are needed to assess their therapeutic potential., Patient Summary: Androgen suppressive therapy is commonly prescribed for the treatment of prostate-related problems. Prior research indicates that there may be a role for these treatments in patients with bladder cancer. In this review, we evaluate the current evidence that strongly suggests that these agents may be effective against bladder cancer., (Copyright © 2020 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Purpose: To assess whether receipt of 5-alpha reductase inhibitors (5-ARIs) influences the findings on surgical pathology at the time of radical cystectomy (RC) and subsequent clinical outcomes. 5-ARIs may slow the progression of non-muscle-invasive bladder cancer., Patients and Methods: We retrospectively reviewed all patients who underwent RC at our institution between 2009 and 2017. Men were included who had urothelial cancer in the RC specimen. Patients with nonurothelial pathology or who had no cancer in the specimen were excluded. Odds ratios for pathologic features and hazard ratios for survival were adjusted for baseline patient characteristics and disease stage., Results: Our study cohort included 338 men; 48 patients (14%) were receiving dutasteride or finasteride at time of RC, 58 (17%) metformin, and 195 (58%) statins. Among patients receiving 5-ARIs, there was a lower proportion of positive margins (P = .08) and lymphovascular invasion (P = .05). This was statistically significant when patients with urothelial carcinoma variants were excluded. Multivariable logistic regression analysis demonstrated that 5-ARI receipt was associated with a lower odds ratio (OR) for the presence of lymphovascular invasion (OR = 0.49; 95% confidence interval, 0.24-1.00; P = .049) and positive surgical margins (OR = 0.30; 95% confidence interval, 0.09-1.07; P = .063). Further, 5-ARI receipt was associated with better overall survival, with an adjusted hazard ratio of 0.40 (95% confidence interval, 0.19-0.83; P = .015). No similar tendencies were observed with metformin or statins., Conclusion: 5-ARIs may exert a protective biologic effect on the invasive properties of high-grade urothelial carcinoma. Further research is needed to understand the therapeutic implications., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objectives: To assess the rate of urinary tract infection (UTI), the characteristics of the bacterial aetiological agents involved, the type and duration of antibiotics used, and the clinical risk factors of UTI in a multi-institutional cohort of patients who had undergone radical cystectomy (RC)., Patients and Methods: The pre- and postoperative characteristics of patients who had undergone open RC at 1 of 3 institutions between 2009 and 2015 were analyzed by means of the patient charts. Patients were classified according to the presence or absence of UTI. Analysis of the severity of UTI was based on the EAU/EAU Section of Infections in Urology (ESIU) classification system. The bacterial aetiological agents and their antibiotic susceptibility were also assessed. Factors predicting postoperative UTI were identified using univariable and multivariable logistic regression analysis., Results: Of 217 patients, 42 (19.4%) had developed postoperative UTI, of whom 50% had urosepsis or uroseptic shock. Multivariable analysis showed continent urinary derivation as the only significant predictor of UTI with an odds ratio of 5.03 (95% confidence interval 2.12-11.9, P < 0.001). The duration of perioperative antibiotic prophylaxis was not associated with an increased risk of UTI. Enterococcus was the most commonly isolated bacteria (25.7%), but this species is not covered by the recommended antibiotic prophylaxis., Conclusion: Patients with continent urinary diversion after RC have a significantly higher risk of developing UTI. Prolonged perioperative administration of antibiotics does not seem to reduce the risk of UTI. Enterococcus as the most commonly isolated bacteria is not covered by most recommended antibiotic prophylaxis regimens. Therefore different antibiotic regimens should be considered for high-risk patients., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: Radical cystectomy (RC) can be associated with significant blood loss, whereas many patients are presenting with anemia preoperatively. To date, there is a lack of data addressing the impact of preoperative anemia (PA) on survival of patients undergoing RC for urothelial carcinoma of the bladder (UCB)., Methods: This retrospective multicenter study includes 684 patients with UCB undergoing RC with pelvic lymph node dissection. The median follow-up was 50 (IQR 29,78) months. Anemia was defined in line with the WHO classification (hemoglobin (Hb): male ≤13 g/dL, female ≤12 g/dL) and based on contemporary gender- and age-adjusted classification (Hb: white male aged <60 years: ≤13.7 g/dL; ≥60 years: ≤13.2 g/dL; white female of all ages ≤12.2 g/dL). Univariable and multivariable Cox regression analyses were used to assess the effects of PA on oncological outcomes., Results: A total of 269 (39.3 %) and 302 (44.2 %) patients were anemic according to the WHO classification versus contemporary classification. Age, increased ECOG performance status, advanced tumor stages, lymph node metastasis, positive surgical margin and anemia were associated with disease recurrence (DR), cancer-specific mortality (CSM) and all-cause mortality (ACM). In multivariable analysis, anemia was an independent predictor of DR, CSM and ACM (WHO and/or contemporary classification). Blood transfusion was significantly associated with ACM in both classifications of anemia., Conclusions: PA is significantly associated with worse oncological outcome in patients undergoing RC. Based on the additional unfavorable influence of blood transfusion, this emphasizes the importance of early diagnosis and correction of anemia and implementation of alternative methods of blood volume management.

Introduction: The purpose of this study was to evaluate and compare complications after radical cystectomy in patients aged ≥75 years., Materials and Methods: 251 patients aged 75-95 years (median 79) underwent radical cystectomy between 2000 and 2012 at four institutions. The patients were divided into two groups: ≥75-84 years of age (group 1) versus ≥85 years of age (group 2). Comorbidities, body mass index, and complications were obtained retrospectively, except at the Central Hospital of Bolzano and Weill Cornell Medical Center, which collected data prospectively. Cancer-specific survival, overall mortality, hospital stay, clinical outcome and complications were assessed. Complications were categorized using the Clavien-Dindo classification reporting system. The mean follow-up was 21 months., Results: The median hospital stay was 17 (2-91) days. Perioperative Clavien-Dindo grade ≥III complications were seen in 24.1% (48/199) of group 1 patients and 19.2% (10/52) of group 2 patients (p = 0.045). 30- and 90-day mortality was 4.5 and 13.5% in group 1 and 6.5 and 32.3% in group 2, respectively. Only the 90-day mortality rate was statistically significant (p < 0.05) between the two groups. The 3-year overall survival was 40% in group 1 and 34% in group 2. The 3-year cancer-specific survival was 52% in group 1 and 50% in group 2., Conclusions: We evaluated a large series of elderly (≥75 years) patients undergoing radical cystectomy at four institutions. Comparing patients aged ≥75-84 and ≥85 years revealed no significant difference in complications, 30-day mortality, overall and cancer-specific survival rates. Only 90-day mortality rates were significantly higher in the ≥85-year-old patients., (© 2014 S. Karger AG, Basel.)

Objectives: Bladder perforation is the second most common complication during transurethral resection of bladder tumours. It is unknown whether perforation affects the natural history of the tumour through cell seeding. The aim of this study was to study the impact of perforation on the oncologic outcomes of bladder carcinoma., Materials and Methods: Between 2003 and 2007, 926 consecutive patients underwent transurethral resection of bladder tumours at our institution; 327 cases were staged ≥ pT2 and were treated immediately with cystectomy and/or multimodal therapy and therefore excluded from the study. An additional 34 cases without urothelial carcinoma were excluded. Of the remaining 565 patients with non-muscle invasive bladder cancer, 457 (80.8 %) were male and 108 (19.2 %) were female with a mean age of 69.5 years in men and 67.3 years in women. Thirty-seven patients (6.5 %) experienced bladder perforation at the time of tumour resection. This group of patients (Group 1) was compared to the remaining 528 patients (Group 2) who did not experience a bladder perforation., Results: Patients with bladder wall perforation experienced a shorter disease-free survival in both univariate (p = 0.003) and multivariate analyses (p = 0.006). In addition, subsequent recurrences revealed stage progression of recurrent disease (p = 0.05) and trended to a higher number of cystectomies in the perforated group of patients (p = 0.06). Nevertheless, perforation did not appear to influence overall survival (p = 0.127) or cancer-specific survival (p = 0.141)., Conclusion: The results indicate that bladder perforation during resection of superficial bladder tumours is burdened by a shortened disease-free survival and T-stage progression.

Objective: To test the prognostic value of multicolor fluorescence in situ hybridization analyses of tumor cells in urine for prediction of the recurrence and progression of tumor in patients with intermediate risk non-muscle invasive bladder cancer., Methods: A total of 168 patients with non-muscle invasive bladder cancer were included in the study. Fluorescence in situ hybridization was carried out on the bladder wash urine collected before resection. Tumors were classified as low molecular grading if they had a diploid chromosomal pattern or only a loss of p16 or ch3 aneuploidy, and as high molecular grading if they showed aneuploidy of ch7 or 17. Cox regression models assessed the added prognostic value of fluorescence in situ hybridization for primary tumor recurrence or progression, respectively., Results: Median follow up was 67 months. A total of 57% of tumors were classified as low molecular grading. The 2- and 5-year recurrence-free survival was 68% and 49% for low molecular grading, and 47% and 30% for high molecular grading, respectively. The 2- and 5-year progression-free survival was 95% and 84% for low molecular grading, and 79% and 58% for high molecular grading tumor patients, respectively. Molecular grading (hazard ratio 1.60; P = 0.03) was associated with recurrence, when also accounting for histopathology and a patient's characteristics. Both cancer severity score (hazard ratio 1.51; P < 0.01) and molecular grading (hazard ratio 2.53; P < 0.01) independently and positively predicted progression in multivariable models. The C-index for predicting recurrence increased from 0.58 to 0.61 when molecular grading fluorescence in situ hybridization was included in the model, and from 0.68 to 0.72 when predicting progression., Conclusions: Fluorescence in situ hybridization-based molecular grading increases the accuracy of a prognostic model, predicting both recurrence and progression in patients with intermediate risk non-muscle invasive bladder cancer., (© 2014 The Japanese Urological Association.)

Aim: To examine the long-term follow-up of patients with that previously underwent risk stratification based on multicolour FISH testing., Patients and Methods: On 81 patients with intermediate-risk urothelial carcinoma, a multicolour-FISH was performed. Patients were sub-divided into low- and high-risk groups based on chromosomal patterns. Univariate analysis, using Mantel-Cox log-rank test for disease-free, progression-free survival and overall survival, was employed to determine the prognostic significance of FISH analysis. Survival times were calculated according to the Kaplan-Meier product-limit method and multivariate analysis using Cox proportional hazards regression model., Results: The univariate Mantel-Cox log-rank test showed significant differences between the low-risk and the high-risk group for disease-free survival (p=0.005) and overall survival (p=0.038), but not for progression-free survival (p=0.129)., Conclusion: Our long-term follow-up data appear to be able to divide tumors into low and high risk groups for recurrence based on molecular/genetic changes observed with FISH., (Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Objective: To identify prognostic clinical and histopathological parameters, including comorbidity indices at the time of radical cystectomy (RC), for overall survival (OS) after recurrence following RC for urothelial carcinoma of the bladder (UCB)., Materials and Methods: A retrospective multicenter study was carried out in 555 unselected consecutive patients who underwent RC with pelvic lymph node dissection for UCB from 2000 to 2010. A total of 227 patients with recurrence comprised our study group. Cox proportional hazards regression models were calculated with established variables to assess their independent influence on OS after recurrence., Results: The median time from RC to recurrence and the median OS after recurrence was 10.9 and 5.4 months, respectively. Neither the time to recurrence nor the type of recurrence (systematic vs. local) was predictive of the OS. In contrast, age (hazard ratio (HR) 1.53, p = 0.011), lymph node metastasis (HR 1.56, p = 0.007), and positive surgical margins (HR 1.53, p = 0.046) significantly affected the OS after disease recurrence. In addition, the dichotomized Charlson comorbidity index (CCI; dichotomized into >2 vs. 0-2) was the only comorbidity score with an independent prediction of OS (HR 1.41, p = 0.033). We observed a significant gain in the base model's predictive accuracy, i.e. from 68.4 to 70.3% (p < 0.001), after inclusion of the dichotomized CCI., Conclusions: We present the first outcome study of comorbidity indices used as predictors of OS after disease recurrence in patients undergoing RC for UCB. The CCI at the time of RC had no significant influence on the time to recurrence but represented an independent predictor of OS after disease recurrence., (2014 S. Karger AG, Basel.)

Introduction: The aim of this study was to compare overall survival in elderly patients (≥ 80 years) with muscle-invasive bladder cancer (MIBC) undergoing either radical cystectomy (RC) or conservative treatment., Material and Methods: We performed a retrospective, comparative analysis of overall- and cancer-specific survival in octagenarians with MIBC (≥ pT2) submitted to RC or conservative treatment. Uni- and multivariable Cox regression analysis were performed to assess predictors of overall survival. Cumulative hospital stay was also analyzed for all patients., Results: The RC-group consisted of 33 patients with a mean age of 82.3 years (IQR 80.4-85.4 years) and the bladder preservation a cohort of 35 patients aged 83.8 years (IQR 81.8-88.2 years). No difference was detectable for overall survival (15.9 months versus 9.5 months; p = 0.18) and cancer-specific survival (23.5 months versus 19.5 months p = 0.71) or 90-day mortality (6.1% versus 14.3%; p = 0.43) between the two groups. Patients who received conservative treatment had a shorter cumulative length of hospital stay (p = 0.001). Age at the time of transurethral resection of the bladder (TUR-B) was an independent predictor of the overall survival (p = 0.004)., Conclusions: In this retrospective study, no clear survival benefit was observed for patients ≥80 years submitted either to radical cystectomy or conservative treatment. There was however a trend favoring radical cystectomy but this did not approach statistical significance. Octagenarians that underwent RC however spent more of their remaining lifetime in the hospital than those treated conservatively.

Background: The aim of the current study was to report the results of 7422 uCyt+/ImmunoCyt and cytology analyses that were performed over the course of 9 years at the study institution for the evaluation and follow-up of patients with urothelial carcinoma., Methods: Between January 2002 and March 2011, 2217 patients with a mean age of 69.5 years (range, 15 years-99 years) were enrolled in the current study. All patients seen for the follow-up of bladder and/or upper tract urothelial cancer as well as those with a history that was suspicious for bladder cancer were recruited. In all patients, a voided urinary cytology and uCyt+/ImmunoCyt test was performed. Patients underwent routine cystoscopy as well as cystoscopy when cytology and/or the uCyt+/ImmunoCyt test yielded positive results. Lesions that were detected cystoscopically were biopsied and removed transurethrally. A total of 7422 uCyt+/ImmunoCyt and cytology analyses were performed., Results: Of the 7422 uCyt+/ImmunoCyt tests and cytologies that were performed, 7075 (95.3%) were considered adequate. A total of 578 patients (with 1156 analyses) underwent biopsy and 728 (63%) samples had a histologically proven urothelial carcinoma. Overall sensitivity was 34.5% for cytology, 68.1% for uCyt+/ImmunoCyt, and 72.8% for the 2 tests combined. Overall specificity was 97.9% for cytology, 72.3% for uCyt+/ImmunoCyt, and 71.9% for the 2 tests combined. Cytology and the uCyt+/ImmunoCyt test together had an overall sensitivity of 72.8%, with 59% for grade 1, 77% for grade 2, and 90% for grade 3 tumors (according to the 1973 World Health Organization grading classification system)., Conclusions: On the basis of their 9-year experience, the authors confirm the value of uCyt+/ImmunoCyt and cytology analyses in the follow-up of patients with non-muscle-invasive urothelial cancer. This could potentially reduce the number and cost of routine cystoscopic examinations in patients who are followed for bladder carcinoma. Cancer (Cancer Cytopathol) 2013;121:392-397. © 2013 American Cancer Society., (© 2013 American Cancer Society.)

Introduction: The aim of the study was to assess the strength of the online tool RiskCheck Bladder Cancer©, version 5.0 (RCBC) for early detection of bladder cancer (BC)., Materials and Methods: RCBC was evaluated retrospectively based on the data of 241 patients, of which 141 were suffering from BC. Statistical analysis was performed by descriptive statistics, nonparametric group comparison, classification tree analysis and ROC analysis., Results: ROC analysis of the risk classification showed a sensitivity of 71.6%, a specificity of 56.5%, a positive predictive value of 67.8%, a negative predictive value of 52% and an accuracy of 63.5%. BC risk factors ranked by importance are time of smoking (p < 0.0001), gender (within the nonsmoking group: p < 0.009), occupational toxin exposure (within the group <35 years of smoking: p < 0.048) and amount of consumed cigarettes resulting in a 95% association with BC (within the group >35 years of smoking: p < 0.0001)., Conclusions: The high predictive power of RCBC for the identification of asymptomatic patients living under risk could be demonstrated., (© 2013 S. Karger AG, Basel.)

Objective: A second transurethral resection of the bladder (TURB) is recommended for high-grade bladder cancer (BC) yet yields negative results in over half of the cases. Aim of this study was to identify prognostic indicators of a positive second TURB or the need for a subsequent cystectomy., Materials and Methods: The study cohort consisted of 101 patients with high-risk BC (T1G2-3, TaG3, Carcinoma in situ) who underwent second TURB after complete first resection. Age, gender, stage, grade, carcinoma in situ (Cis), tumour number, size, localization, surgeon experience and bladder wash cytology before the second TURB were considered as potential prognostic factors of positive histology at second TURB or the need for subsequent cystectomy., Results: The mean follow-up period was 23.8 months. The study cohort was comprised of 82 males and 17 females. Cytology on bladder wash urine was performed in 85/101 patients and in 39 was negative; 55.5 % of second TURB specimens were negative. The rate of upstaging to ≥T2 was 4.9 %. Cis (OR 8.4; 95 % CI 1.3-54.2; p = 0.03) and positive cytology (OR 6.8; 95 % CI 2.3-19.9; p = <0.01) were independent prognostic factors of a residual tumour in the second TURB. Cytology also correlated with clinical need for cystectomy in the follow-up (HR 6.5; 95 % CI 1.3-30.5; p = 0.02)., Conclusions: CIS and positive cytology prior to second TURB increased the risk of a positive second TURB specimen. A positive cytology also increases the risk of the subsequent need for cystectomy.

Background: Comorbidity and performance indices allow assessment of preoperative health status. However, the optimal tool for use in patients with urothelial carcinoma of the bladder (UCB) who are undergoing radical cystectomy (RC) has not yet been established., Objective: To evaluate correlation of Adult Comorbidity Evaluation-27 (ACE27), Charlson Comorbidity Index, Age-Adjusted Charlson Comorbidity Index, Eastern Cooperative Oncology Group performance status, and American Society of Anesthesiologists (ASA) score with survival., Design, Setting, and Participants: A retrospective multicenter study was carried out on 555 unselected consecutive patients who underwent RC for UCB from 2000 to 2010., Intervention: RC with pelvic lymph node dissection in patients with UCB without neoadjuvant chemotherapy., Outcome Measurements and Statistical Analysis: Cox regression models were calculated with established variables to assess predictive capacity for cancer-specific mortality (CSM) and cancer-independent mortality (CIM)., Results and Limitations: All indices were independent predictors for CIM but not for CSM. The ASA score was the only index that significantly increased the predictive accuracy of the predefined CIM model (+2.3%; p=0.045). To create a clinically valuable tool, we devised a weighted prognostic model including age and the best prognosticators within the performance and comorbidity scores (ASA/ACE27 0-1/2-3). A 3-yr CIM rate of 8%, 26%, and 47% was calculated for the low-, intermediate-, and high-risk groups, respectively. Patients >75 yr of age with ASA 3/4 and ACE27 >1 exhibited a CIM risk seven times greater than patients ≤75 yr with ASA 1/2 and ACE27 0/1. This study is limited by the short follow-up and its retrospective nature., Conclusions: Comorbidity and performance assessment is mandatory in the preoperative prediction of CIM for patients undergoing RC for UCB. The present results indicate that the ASA score is the tool of choice. External and prospective validation is warranted., (Copyright © 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Unlabelled: What's known on the subject? and What does the study add? The degree of comorbidity significantly affects the course of patients with bladder cancer undergoing radical cystectomy (RC). To our knowledge this is the first study comparing four different comorbidity indices in patients undergoing RC for urothelial carcinoma to assess the best clinical predictors for 90-day perioperative mortality. We concluded that the ASA score should be the method of choice, as it showed a predictive ability superior to that of ECOG and CCI, and is much easier to generate than the ACE-27., Objective: To evaluate which of the following among the Adult Comorbidity Evaluation-27 (ACE-27), the Charlson Comorbidity Index (CCI), the Eastern Cooperative Oncology Group performance status (ECOG) and the American Society of Anesthesiologists (ASA) comorbidity scores correlate best with perioperative mortality after radical cystectomy (RC) for urothelial carcinoma (UC) of the bladder., Patients and Methods: A study was carried out on 555 unselected consecutive patients without neoadjuvant chemotherapy who underwent RC for UC of the bladder from 2000 to 2010 at one of two institutions. Patients' medical records were reviewed retrospectively. We established a defined binary linear progression model based on clinical variables to predict perioperative mortality <90 days after RC (90PM). To this model we added, individually, the comorbidity indices ACE-27, CCI, ECOG, and ASA to assess their predictive capacity regarding 90PM., Results: The overall 90PM was 7.9%. Age (P = 0.01) and clinical distant metastatic tumour stage (P = 0.002) were independent predictors for 90PM in the multivariate analysis. Each of the four investigated comorbidity indices was able to significantly increase the predictive capacity of the basic model: ECOG +13.5%, (odds ratio [OR]: 1.61, P = 0.036; area under the curve [AUC] 74.7), ASA Score +28.3% (OR: 2.19, P = 0.004; AUC 76.1), Charlson Index +12.3% (OR: 1.31, P = 0.047; AUC 73.8) and ACE-27 + 29.8% (OR: 1.72, P = 0.004; AUC 76.1)., Conclusions: ASA and ACE-27 show a nearly identical clinical predictive value for perioperative mortality. Both scores could be considered for clinical practice. With regard to ease of generation and availability, the ASA score can be regarded as the best instrument., (© 2012 BJU INTERNATIONAL.)

Objective: To investigate the role of (18) F-fluorodeoxyglusose positron-emission tomography (FDG-PET), combined with computed tomography (CT) and forced diuresis, in the staging and follow-up of urothelial carcinoma (UC)., Patients and Methods: We recruited 44 patients with muscle-invasive urothelial bladder cancer (UBC) before radical cystectomy (RC), 19 under follow-up after RC and seven after systemic chemotherapy. For those who had RC, histopathology was used as the reference standard to compare the sensitivity and specificity of FDG-PET/CT and standard CT in detecting UBC and pelvic lymph node metastasis. Furthermore, 36 patients with ≥ 6 months of follow-up imaging were considered to describe the progression of UC and extrapelvic positive FDG-PET/CT images., Results: For the detection of primary UBC, FDG-PET/CT was slightly more sensitive than CT (85% vs 77%) but less specific (25% vs 50%). For the detection of pelvic node metastasis FDG-PET/CT was more sensitive than CT (57% vs 33%) with a specificity of 100% for both imaging techniques. In 20 patients, extrapelvic FDG-PET/CT images showed suspected disease at the first evaluation. UC progressed in nine of the 10 patients who had synchronous multiple PET-positive retroperitoneal or mediastinal lymph nodes, and in only two of the nine with unique hyperactive lesions in the lung. FDG-PET/CT also detected a pT1G3 UC of the renal pelvis and all bone metastases detected by bone scintigraphy., Conclusions: FDG-PET/CT could replace standard CT and bone scintigraphy in the presurgical staging and monitoring of patients with UC after surgery or chemotherapy., (© 2010 THE AUTHORS. JOURNAL COMPILATION © 2010 BJU INTERNATIONAL.)

Purpose of Review: To review the most recent publications focusing on the use of genetic markers (DNA, RNA and nucleosides) in urine and serum and provide an opinion on their potential utility for screening, diagnosis and prognosis of urothelial carcinoma., Recent Findings: Several studies have shown the diagnostic utility of urine tests based on improved microsatellite analysis of loss-of-heterozygosity, detection of fibroblast growth factor receptor 3 mutations, detection of single RNA and multiple gene signatures as well as nucleoside profiles. Although of interest, all these studies lack appropriate controls and validation before being considered as serious candidate clinical biomarkers. The presence of fibroblast growth factor receptor 3 mutations in tumors was identified as a hallmark of tumors of low malignant potential. Serum DNA analysis of hypermethylation of a set of genes shows promise as an indicator of cancer progression and mortality. Finally, a case-control study of 775 patients and 397 controls showed that DNA hypomethylation of blood cells combined with smoking habits can provide stratification of cancer risk that may be very helpful in conceiving bladder cancer screening studies., Summary: The challenge is not so much to identify better markers or methods but rather to commit to implementing them into clinical practice by stimulating and funding the clinical trials required.

Aim: To establish independent prognostic factors on a chromosomal basis in superficial bladder cancer, using a multicolour fluorescence in situ hybridisation (FISH) probe mix., Patients and Methods: In 2002, voided urine from 75 consecutive patients (mean age 71.7, range 52-93) years under follow-up for superficial urothelial cancer was studied prospectively. The patients were observed for a mean (standard deviation (SD)) period of 39.3 (6.8) months (range 27-58) until July 2005. A multicolour FISH on liquid-based voided urinary cytology was carried out on all patients. Univariate analysis, using a log rank test, was used to determine the prognostic relevance of a low-risk pattern and a high-risk pattern. Progression-free survival time was calculated from the date of first diagnosis to first recurrence or progression according to the Kaplan-Meier product-limit method., Results: One patient was lost to follow-up. 27 of the 74 remaining (36.8%) patients showed recurrent disease. In 9 (33.3%) patients with a low-risk pattern disease recurred after a mean (SD) observation time of 29.7 (1.9) months (range 8.3-52.3, median 30.8 (12.4)). 18 (66.7%) patients with a high-risk pattern developed recurrence within a mean (SD) of 17.6 (2.0) months (range 4-38.8, median 16.7 (11.6)). The Kaplan-Meier curve for progression-free survival showed marked differences between the low-risk and the high-risk groups., Conclusion: Patients with a high-risk chromosomal pattern have a markedly shorter disease-free survival time and higher progression rate than patients with a low-risk pattern. High-risk patients can therefore be treated more aggressively to prevent tumour spreading.

Objectives: To assess the utility of ImmunoCyt/uCyt+ in combination with cytology to reduce the number and cost of cystoscopies in the follow-up of patients with urothelial cancer of the bladder., Methods: A total of 216 patients under follow-up after transurethral resection of the bladder for urothelial cancer were enrolled in the present study. The mean follow-up time was 26 months (range 3 to 96). Patients were tested for bladder cancer with ImmunoCyt/uCyt+, urinary cytology, and cystoscopy every 3 months. All patients with positive cystoscopy results for recurrence or suspect areas underwent transurethral resection of the bladder. Cystoscopy was considered the reference standard to establish the bladder tumor diagnosis. The patients were divided into low, intermediate, and high risk groups for progression according to the European Association of Urology criteria., Results: A total of 195 patients were suitable for evaluation. The urine samples from 21 patients were considered not evaluable for ImmunoCyt/uCyt+, and those patients were excluded from the study. Of all the control patients, 69.7% had negative cystoscopy findings. In the low-risk group, 84 patients underwent 131 cystoscopies, which diagnosed 30 Stage pTaG1 recurrences but no progression. Cytology and ImmunoCyt/uCyt+ together had a sensitivity of 86.6% and a negative predictive value of 95.2%., Conclusions: Of the cystoscopies performed during the 26 months of follow-up, 69.7% were negative. In the low-risk group, 30 Stage pTaG1 tumors and no progression was detected at a total cost of 14,672 Euros (USD 17,606). ImmunoCyt/uCyt+ and cytology every 6 months combined with annual cystoscopy reduced the morbidity and cost of follow-up in this group.

Background: The authors provide an update on the clinical value and role of the uCyt+/ImmunoCyt test as a noninvasive tool for the detection of recurrent urothelial carcinoma., Methods: Between January 2002 and October 2004, 942 patients (mean age, 72.6 yrs; range, 32-87 yrs) were enrolled in this prospective study. These patients mostly had been followed for superficial urothelial carcinoma (UC) confined to the mucosa and lamina propria (pathologic tumor [pT] classification pTa, pT1, and pTis [carcinoma in situ]) for a mean of 15.62 months (range, 4-28 mos). Voided urinary cytology and the uCyt+/ImmunoCyt test for all patients were performed on liquid-based cytology slides. Patients underwent subsequent cystoscopy when cytology or uCyt+/ImmunoCyt results were positive and when they underwent biopsy evaluation of any suspicious lesion. Altogether, 1991 uCyt+/ImmunoCyt analyses were performed., Results: Two hundred ninety-eight patients who had adequate samples available were diagnosed with histologically proven UC. The sensitivity of cytology increased from 8.3% for Grade 1 tumors to 75.3% for Grade 3 tumors; whereas, with the uCyt+/ImmunoCyt, the sensitivity was 79.3% for Grade 1 tumors, 84.1% for Grade 2 tumors, and 92.1% for Grade 3 tumors. For cytology and uCyt+/ImmunoCyt combined, the sensitivity was 79.3% for Grade 1 tumors, 90.9% for Grade 2 tumors, and 98.9% for Grade 3 tumors., Conclusions: The current data confirmed the clinical usefulness of the uCyt+/ImmunoCyt test in the follow-up of patients with recurrent UC. Used as a noninvasive tool, cytology escorted by uCyt+/ImmunoCyt may reduce the morbidity and cost of follow-up for patients who have a low risk of recurrence while avoiding superfluous cystoscopic examinations. However, additional studies will be necessary to establish and compare the morbidity and cost of each method., ((c) 2006 American Cancer Society.)

Background: Urine bound tests, which have been developed for the early detection of urothelial cancer (UC), do not seem to match cytology in the detection of carcinoma in situ (CIS) as their sensitivity in the case of CIS is poor. ImmunoCyt/uCyt+ in CIS seems promising, but the number of analysed CIS is still small. The aim of the present study was to assess the value of this test in the detection and follow-up of carcinoma in situ of the urinary bladder., Patients and Methods: Thirty-five patients, with histologically verified CIS of the urinary bladder, were included in the study. At the first diagnosis, patients underwent cytology, cystoscopy, bioptical bladder mapping and ImmunoCyt/uCyt+. All patients underwent BCG instillation therapy. The patients were followed with cytology, ImmunoCyt/uCyt+, cystoscopy and bladder mapping after every BCG cycle and then every 3 months., Results: At the first CIS diagnosis, the sensitivity of cytology and ImmunoCyt/uCyt+ was 100%. At the first control after therapy, cytology detected 81.8% of recurrences and ImmunoCyt/uCyt+ detected 90.9%. At the second control, both tests each detected 50% of recurrences. At every control, the combination of both the tests together gave a sensitivity of 100%. The specificity of cytology after therapy improved from 88.2% at the first control up to 100% at the third control. The specificity of ImmunoCyt/uCyt+ after BCG initially decreased from 70.6% to 55.5% and finally increased to 88.9%., Conclusion: ImmunoCyt/uCyt+ is as sensitive as cytology in the first diagnosis of CIS. In the follow-up, even if it is less sensitive, its combination with cytology leads to detection of 100% of the recurrences. Despite decreasing specificity after therapy, the value remains acceptable and increases during maintenance therapy. The ImmunoCyt/uCyt+ test could play an important role in controlling the response of patients to instillation therapies or in the modification of their application schedules.

Objectives: To evaluate the bladder preservation strategy in invasive bladder cancer particularly relapse, progression and complications., Materials and Methods: From January 2000 to May 2004 a total of 24 patients (mean age of 81 years; range 68-92) with muscle invasive bladder cancer who had refused or were not eligible for cystectomy were followed up for a period of up to four years., Results: 24 (21 M/3 F) patients were followed up for a mean time of 680 (182-1253) days. All patients complained of frequency, urgency and severe nocturia. The second most frequent complication was bleeding which required a salvage cystectomy in 7 cases. Other major complications were intestinal occlusion in three cases, an enterovesical fistula, brain metastasis requiring neurosurgical intervention and radiation therapy of the brain, bone metastasis in the cervical spinal column and chronic renal failure. The mean re-admission rate was 8 per patient and the mean time spent at the hospital was 109 (range 13-253) days., Conclusion: In our series the bladder preserving strategy does not confirm the optimistic results of other authors. The complications forced us to carry out a salvage cystectomy in nearly half of the cases. The other half of the patients complained of other severe complications reducing the quality of life of the remaining life span.

Unlabelled: The tubularized-incised plate urethroplasty has traditionally been used in children for repairing hypospadias. As shown here, it can also be used successfully in adults, with very good results. The rate of wound healing, infection and complications is the same as in children, as are the cosmetic and functional outcomes., Objectives: To evaluate the outcome of uretero-ureterocutaneostomy (UUC) wrapped by omentum for palliative cystectomy in symptomatic elderly high-risk patients with high-stage bladder cancer., Patients and Methods: The study included 15 patients (14 men and one woman, aged 72-87 years, American Society of Anesthesiology score 3) with symptomatic recurrent bleeding bladder cancer (T2/T3) who were treated with palliative cystectomy. UUC was performed by mobilizing the right pre-vesical divided ureter up to the pelvi-ureteric junction and a high retroperitoneal crossover to the divided left ureter. A stoma was created with a circular 2-cm skin excision and resecting the fatty subcutaneous tissue. Wrapped by the omentum, both well-vascularized ureteric stumps were pulled through a cross-like fascia incision up to skin level. Spatulated and everted, the 'butterfly' flaps were fixed to the skin and underlying omentum. Soft splints were inserted for 21 days and a Karaya ring placed., Results: The postoperative course and stoma healing was normal in 14 of the 15 patients; the sigmoid was resected because of sigmoid diverticulitis in one. The median (range) follow-up was 15 (6-24) months. There was pyelonephritis in one patient, and the dilatation of the upper tract (grade 3) in two returned to grade 2, with new asymptomatic grade 1 dilatation in one other. All patients were without stents and stoma care was provided at home., Conclusions: This modified UUC by omental wrapping in 15 high-risk patients after palliative cystectomy was simple and safe, and their recovery was uneventful. To date the few patients with stomal obstruction were managed by J catheters, changed every 4-6 months.

Objectives: To assess the influence of intravesical instillation of epirubicin or bacille Calmette-Guérin (BCG) in patients with bladder cancer on the clinical performance of the uCyt+ test, which traces the three monoclonal antibodies M344, LDQ 10, and 19A211 in urothelial cells., Methods: A total of 267 patients with a mean age of 70.5 years (range 35 to 87) were included in this prospective study. All patients were being followed up after complete transurethral resection of superficial urothelial cancer. All patients received a single instillation of 80 mg epirubicin within 24 hours of transurethral resection and 163 underwent subsequent cycles of chemotherapy with epirubicin or immunotherapy with BCG. This was because of multifocality, high-recurrence, or high-grade urothelial cancer. At the next control, all patients underwent urinary cytology, with the uCyt+ test performed on liquid-based cytology (ThinPrep), subsequent cystoscopy, and evaluation of any suspicious lesion by biopsy. Patients who underwent intravesical BCG therapy underwent random bladder cold biopsy after every instillation series., Results: Of the 267 patients, 8 could not be evaluated by uCyt+ because of insufficient cells. Of the remaining 259 patients under assessment, 86 had proven urothelial cancer. In the 101 patients under assessment with only a single intravesical instillation of epirubicin (group 1), the overall sensitivity for cytology and the uCyt+ test was 44.7% and 76.6%, respectively. Cytology had a specificity of 90.7% and uCyt+ of 64.8%. The negative predictive value for cytology and uCyt+ was 65.3% and 76.1%, respectively. Of the 158 patients under evaluation who were treated with long-term intravesical therapy (group 2), the overall sensitivity and specificity for cytology and the uCyt+ test was 37.8% and 84.6% and 94.9% and 70.6%, respectively. The negative predictive value for cytology and the uCyt+ test was 83.1% and 93.3%, respectively. Statistical analysis showed no statistically significant difference between the overall sensitivity (P = 0.512) and specificity (P = 0.558) for the uCyt+ test in the two groups of patients., Conclusions: The sensitivity and specificity of the uCyt+ test are not significantly affected by intravesical long-term treatment with epirubicin or BCG.

Objectives: To perform a biologic characterization of the urothelial neoplasms of patients in the intermediate-risk group using multicolor-fluorescence in situ hybridization (FISH). A general consensus has not been reached with regard to the optimal therapy and follow-up of patients with urothelial neoplasms at intermediate risk of progression. On the basis of the chromosomal pattern, we developed a new follow-up algorithm for this group and report our preliminary results., Methods: Voided urine samples of 51 consecutive patients (mean age 72.2 years, range 52 to 93) under follow-up after complete transurethral resection of intermediate-risk urothelial carcinoma were evaluated by liquid-based cytology (ThinPrep) and uCyt+. From the residual material, Multicolor-FISH (Urovysion) was performed. Any cystoscopically suspicious lesion was biopsied or removed transurethrally. The mean follow-up time was 14.2 months (range 6 to 30, SD 5.5)., Results: Two of the 51 patients were not evaluated because of the presence of intense granulocytosis and insufficient urothelial cells. Of the 49 remaining patients, the results of the Multicolor-FISH analysis were negative (diploid chromosomal pattern) in 14; 20 patients showed the loss of one or both alleles of p16 and/or an aneuploidy of chromosome 3, and 15 patients had aneuploidy of chromosome 7 and/or 17. Of the 14 FISH-negative patients, 2 (14.3%) had histologically verified recurrence, and 3 (15.0%) of the 20 p16/3-positive patients had recurrence and 9 (60.0%) of the 15 7/17-positive patients had either recurrence or progression., Conclusions: Using the Urovysion test, it is possible to predict the biologic behavior of urothelial cancer with a significant impact on the follow-up of patients. The intermediate-risk group of urothelial cancer can be eliminated in the routine workup by classifying these patients according to their chromosomal pattern and defining those patients who can follow the low-risk scheme and those who must be monitored according to the guidelines for high-risk superficial lesions.

Objectives: To evaluate the feasibility and safety of transurethral en bloc resection of bladder tumors using a flat loop. Transurethral en bloc resection of bladder tumors facilitates pathologic evaluation., Methods: A total of 37 patients with papillary transitional cell carcinoma of the bladder underwent transurethral en bloc resection with the use of a flat loop electrode., Results: In 37 patients, 62 lesions were removed using a flat loop to perform the en bloc technique. This method is safe to perform in the case of papillary tumors with a diameter of up to 25 mm and that are found in specific areas of the bladder., Conclusions: It is both safe and feasible to perform en bloc resection with a flat loop electrode but attention must be paid to the limitations of this technique. Excellent pathologic evaluation of the grade and stage of the removed specimen is possible.

The aim of the study was to assess the value of liquid-based urinary cytology as a tool to perform uCyt+ and Multicolour-FISH in patients under follow-up after urothelial cancer. Therefore, standard cytology was compared to liquid-based cytology with the addition of the uCyt+ test, which traces the three monoclonal antibodies M344, LDQ10 and 19A211 in exfoliated urothelial cells; and Multicolour-FISH (including centromere-specific probes for chromosomes 3, 7, 17 and a locus-specific probe for 9p21/p16) performed on thin-layer specimens. UCyt+ showed an overall sensitivity of 86.2% and cytology of 45.0%. Overall sensitivity of both the tests combined was 90%. Sensitivity of Multicolour-FISH was 96.4%. All conventional cytology diagnoses were confirmed by liquid-based cytology. Liquid-based cytology is a valid tool for the performance of adjunctive analyses, such as uCyt+ and Multicolour-FISH, on residual cellular material.

Objectives: To report on our 2-year experience in teaching transurethral resection (TUR) of bladder tumors to five trainees. We analyzed their problems, as well as those of the teachers, and present our solutions., Methods: Between April 2000 and March 2002, five residents and three members of the staff took part in a training program to teach TUR of the bladder. From a total of 692 patients with bladder tumors admitted for treatment to our department, 417 were selected for the study. These 417 had papillary tumors of small to medium size (maximum 25 mm in diameter). The mean patient age was 61 years (range 32 to 92) for men (n = 322; 77%) and 68.4 years (range 48 to 91) for women (n = 95; 33%)., Results: A total of 417 teaching TURs were performed during a 24-month period. A total of 65 complications (16%) occurred and were analyzed from the database. The most common complication was postoperative bleeding, occurring in 33 cases (8%), followed by extraperitoneal perforation, which occurred in 16 cases (4%)., Conclusions: Despite careful patient selection and the use of video-assisted equipment and permanent supervision by an experienced resectionist, a significant number of complications occurred. The question: "How to teach the teacher to teach TUR of the bladder?" remains open.

Objectives: To test the clinical value and role of uCyt+ as a noninvasive tool for the detection and surveillance of urothelial carcinoma., Methods: Included in this prospective study were 235 patients (mean age 71.5 years, range 32 to 86). Of these, 98 patients had signs and symptoms suggestive of bladder cancer and 137 patients were being followed up after complete transurethral resection of superficial urothelial cancer (UC). All patients underwent urinary cytology and the uCyt+ test performed on ThinPrep (thin layer). All underwent subsequent cystoscopy and evaluation of any suspicious lesion by biopsy., Results: A total of 102 patients had histologically proven UC. In the group of patients with signs and symptoms suspicious of UC, the sensitivity of cytology increased from 5% for G1 to 84.6% for G3 tumors; for uCyt+, it was 85% for G1, 100% for G2, and 92.3% for G3 tumors. Combining cytology and uCyt+, the sensitivity was 85% for G1 and 100% for G2 and G3. In the group of follow-up patients, the sensitivity of cytology increased from 4.3% for G1 to 94.4% for G3 tumors; for uCyt+, it was 78.2% for G1, 70% for G2, and 94.4% for G3 tumors. Combining both tests, the sensitivity was 78.2% for G1, 90% for G2, and 100% for G3., Conclusions: The uCyt+ is a valid test in the detection of UC of all grades and stages. It improves the sensitivity of cytology in low-grade tumors. The two tests combined may be a highly sensitive method to detect UC early in detection and surveillance.

Objectives: To compare the diagnostic value of two rapid tests, the bladder tumor antigen (BTA stat) test and the newly developed urinary bladder cancer (UBC) Rapid test, in patients having symptoms suggestive of urothelial cell carcinoma (UCC) and patients being followed up after transurethral resection., Methods: One hundred eighty patients with a mean age of 65.8 years (range 22 to 92) were included in the present study. The tests were performed on voided urine samples. Fifty-seven patients had symptoms suggestive of UCC and 123 patients were being followed up after complete transurethral resection of UCC. The voided urine was evaluated by the BTA stat and UBC Rapid test, which detects cytokeratins 8 and 18. All patients underwent subsequent cystoscopic evaluation and biopsy of any suspicious lesion., Results: In 53 patients with histologically proved UCC, the BTA stat had a sensitivity of 52.8% and the UBC Rapid test of 66%. According to the histologic stage, the sensitivity of the BTA stat was 42.8% in pTa tumors, 61.5% in pT1, and 70% in pT2 or higher tumors. The sensitivity of the UBC test was 60.7% in pTa, 69. 2% in pT1, and 80% in pT2 or higher tumors. For histologic grades 1 to 3, the sensitivity was 38.8%, 52.6%, and 68.7% for the BTA stat and 44.4%, 78.9%, and 75% for the UBC Rapid test, respectively. The specificity was 70% and 90% for the BTA stat and UBC Rapid test, respectively., Conclusions: The UBC Rapid test was superior to the BTA stat in both sensitivity and specificity. Both assays are simple office procedures and require no special knowledge. However, they cannot replace, but only lower, the number of cystoscopies during the follow-up of patients with previous UCC of the bladder.

Objectives: To compare the diagnostic value of two enzyme-linked immunosorbent assay (ELISA) tests, the nuclear matrix protein 22 (NMP22) test and a newly developed urinary bladder cancer (UBC) test, in patients having symptoms suggestive of urothelial cell carcinoma (UCC) and patients under follow-up after transurethral resection (TUR)., Methods: Two hundred forty patients with a mean age of 65.8 years (range 22 to 92) were included in this retrospective study. The tests were performed on previously frozen urine samples. Eighty-one patients had symptoms suggestive of bladder cancer and 159 patients were being followed up after complete TUR of UCC. Voided urine was evaluated by the NMP22 test and the monoclonal UBC-ELISA test, which traces cytokeratins 8 and 18. All patients underwent subsequent cystoscopy and biopsy evaluation of any suspicious lesion. The cutoff levels for bladder cancer positivity were 10 U/mL for the NMP22 test and 12 microg/L for the UBC test., Results: In the 54 patients with histologically proved UCC, the NMP22 test had a sensitivity of 55.5% and the UBC test a sensitivity of 64.8%. According to the histologic stages, the sensitivity of NMP22 was 51.7% in pTa tumors, 46.1% in pT1, and 70% in pT2 or higher tumors; the sensitivity of UBC was 62.1% in pTa, 53.8% in pT1, and 80% in pT2 or higher tumors. For histologic grades 1 to 3, the sensitivity was 50%, 50%, and 68.7% for NMP22 and 66.6%, 60%, and 68.7% for UBC, respectively. The specificity was 79% and 92% for NMP22 and UBC, respectively., Conclusions: The monoclonal UBC-ELISA test is superior to the NMP22 test in both sensitivity and specificity. Nevertheless, neither test can replace cystoscopy.