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Patients with non-muscle-invasive bladder cancer (NMIBC) in the intermediate and high-risk groups must receive adjuvant treatment with intravesical Bacillus Calmette-Guérin (BCG) following transurethral resection (TUR), as it reduces the risk of recurrence and presumably the risk of progression as well. Optimization of BCG efficacy is achieved by administering maintenance therapy. However, since many immunological aspects of the mechanism of action of BCG in the bladder remain unknown, the implementation of the optimal dose, number of instillations, strains and adequate maintenance regimen over the last decades has been heterogeneous. Additionally, this has hindered the interpretation of efficacy in terms of oncologic outcomes. This, together with the shortages of BCG in recent years, have forced scientific societies to adapt their clinical practice guidelines and modify their protocols of adjuvant treatment with BCG. This includes changes to strains, doses, and maintenance during this period of time. This consensus document evaluates the current status of adjuvant BCG treatment and the implications of BCG supply availability in the treatment of patients with NMIBC. It also addresses the implementation of novel therapies that will improve cancer prognosis and the quality of life of patients with NMIBC in the future., (Copyright © 2024 AEU. Published by Elsevier España, S.L.U. All rights reserved.)

Bacillus Calmette-Guérin (BCG) is the standard of care for patients with high-risk non-muscle-invasive bladder cancer (NMIBC) after transurethral resection of bladder tumor (TURBT). BCG in combination with programmed cell death-1 (PD-1) inhibitors may yield greater anti-tumor activity compared with either agent alone. CREST is a phase III study evaluating the efficacy and safety of the subcutaneous PD-1 inhibitor sasanlimab in combination with BCG for patients with BCG-naive high-risk NMIBC. Eligible participants are randomized to receive sasanlimab plus BCG (induction ± maintenance) or BCG alone for up to 25 cycles within 12 weeks of TURBT. The primary outcome is event-free survival. Secondary outcomes include additional efficacy end points and safety. The target sample size is around 1000 participants.

Background: Treatment options are limited for patients with high-risk non-muscle-invasive bladder cancer (NMIBC) with disease recurrence after bacillus Calmette-Guérin (BCG) treatment and who are ineligible for/refuse radical cystectomy. FGFR alterations are commonly detected in NMIBC. We evaluated the activity of oral erdafitinib, a selective pan-fibroblast growth factor receptor (FGFR) tyrosine kinase inhibitor, versus intravesical chemotherapy in patients with high-risk NMIBC and select FGFR3/2 alterations following recurrence after BCG treatment., Patients and Methods: Patients aged ≥18 years with recurrent, BCG-treated, papillary-only high-risk NMIBC (high-grade Ta/T1) and select FGFR alterations refusing or ineligible for radical cystectomy were randomized to 6 mg daily oral erdafitinib or investigator's choice of intravesical chemotherapy (mitomycin C or gemcitabine). The primary endpoint was recurrence-free survival (RFS). The key secondary endpoint was safety., Results: Study enrollment was discontinued due to slow accrual. Seventy-three patients were randomized 2 : 1 to erdafitinib (n = 49) and chemotherapy (n = 24). Median follow-up for RFS was 13.4 months for both groups. Median RFS was not reached for erdafitinib [95% confidence interval (CI) 16.9 months-not estimable] and was 11.6 months (95% CI 6.4-20.1 months) for chemotherapy, with an estimated hazard ratio of 0.28 (95% CI 0.1-0.6; nominal P value = 0.0008). In this population, safety results were generally consistent with known profiles for erdafitinib and chemotherapy., Conclusions: Erdafitinib prolonged RFS compared with intravesical chemotherapy in patients with papillary-only, high-risk NMIBC harboring FGFR alterations who had disease recurrence after BCG therapy and refused or were ineligible for radical cystectomy., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Transurethral resection of bladder tumor followed by intravesical Bacillus Calmette-Guérin (BCG) is the standard of care in high-risk, non-muscle-invasive bladder cancer (NMIBC). Although many patients respond, recurrence and progression are common. In addition, patients may be unable to receive induction + maintenance due to intolerance or supply issues. Therefore, alternative treatment options are urgently required. Programmed cell death (ligand) 1 (PD-[L]1) inhibitors show clinical benefit in phase 1/2 trials in BCG-unresponsive NMIBC patients. This review presents the status of PD-(L)1 inhibition in high-risk NMIBC and discusses future directions. PubMed and Google scholar were searched for articles relating to NMIBC immunotherapy and ClinicalTrials.gov for planned and ongoing clinical trials. Preclinical and early clinical studies show that BCG upregulates PD-L1 expression in bladder cancer cells and, when combined with a PD-(L)1 inhibitor, a potent antitumor response is activated. Based on this mechanism, several PD-(L)1 inhibitors are in phase 3 trials in BCG-naïve, high-risk NMIBC in combination with BCG. Whereas PD-(L)1 inhibitors are well characterized in patients with advanced malignancies, the impact of immune-related adverse events (irAE) on the benefit/risk ratio in NMIBC should be determined. Alternative routes to intravenous administration, like subcutaneous and intravesical administration, may facilitate adherence and access. The outcomes of combination of PD-(L)1 inhibitors and BCG in NMIBC are highly anticipated. There will be a need to address treatment resources, optimal management of irAEs and education and training related to use of this therapy in clinical practice., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: We aimed to examine how different endoscopic bladder tumor resection techniques affect pathologists' clinical practice patterns., Methods: An online survey including 28 questions clustered in four main sections was prepared by the ESUT ERBT Working Group and released to the pathologists working in the institutions of experts of the ESUT Board and the working groups and experts in the uropathology working group. A descriptive analysis was performed using the collected data., Results: Sixty-eight pathologists from 23 countries responded to the survey. 37.3% of the participants stated that they always report the T1 sub-staging. Of those who gave sub-staging, 61.3% used T1a, b. 85.2% think that en bloc samples provide spatial orientation faster than piecemeal samples, and 60% think en bloc samples are timesaving during an inspection. 55.7% stated that whether the tissue sample is en bloc or piecemeal is essential. 57.4% think en bloc sample reduces turnaround time and is cost-effective for 44.1%. A large number of pathologists find that the pathology examination of piecemeal samples has a longer learning curve., Conclusion: The survey shows that pathologists think that they can diagnose faster, accurately, and cost-effectively with ERBT samples, but they do not often encounter them in practice. Moreover, en bloc samples may be a better choice in pathology resident training. Evidence from real-life observational pathology practice and clinical research can reveal the current situation more clearly and increase awareness on proper treatment in endoscopic management of bladder tumors., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To identify trends in complications following robot-assisted radical cystectomy (RARC) using a multi-institutional database, the International Robotic Cystectomy Consortium (IRCC)., Methods: A retrospective review of the IRCC database was performed (2976 patients, 26 institutions from 11 countries). Postoperative complications were categorized as overall or high grade (≥ Clavien Dindo III) and were further categorized based on type/organ site. Descriptive statistics was used to summarize the data. Multivariate analysis (MVA) was used to identify variables associated with overall and high-grade complications.  Cochran-Armitage trend test was used to describe the trend of complications over time., Results: 1777 (60%) patients developed postoperative complications following RARC, 51% of complications occurred within 30 days of RARC, 19% between 30-90 days, and 30% after 90 days. 835 patients (28%) experienced high-grade complications. Infectious complications (25%) were the most prevalent, while bleeding (1%) was the least. The incidence of complications was stable between 2002-2021. Gastrointestinal and neurologic postoperative complications increased significantly (P < .01, for both) between 2005 and 2020 while thromboembolic (P = .03) and wound complications (P < .01) decreased. On MVA, BMI (OR 1.03, 95%CI 1.01-1.05, P < .01), prior abdominal surgery (OR 1.26, 95%CI 1.03-1.56, P = .03), receipt of neobladder (OR 1.52, 95%CI 1.17-1.99, P < .01), positive nodal disease (OR 1.33, 95%CI 1.05-1.70, P = .02), length of inpatient stay (OR 1.04, 95%CI 1.02-1.05, P < .01) and ICU admission (OR 1.67, 95%CI 1.36-2.06, P < .01) were associated with high-grade complications., Conclusion: Overall and high-grade complications after RARC remained stable between 2002-2021. GI and neurologic complications increased, while thromboembolic and wound complications decreased., (Published by Elsevier Inc.)

Introduction: High grade, non-muscle invasive bladder cancer (NMIBC) is usually treated with intravesical Bacillus Calmette-Guérin. Chemohyperthermia therapy (CHT) may be a novel alternative therapy for the treatment of NMIBC., Objective: To evaluate the recurrence-free survival (RFS) of patients treated with CHT using the Combat bladder recirculation system (BRS) for NMIBC., Methods: This was a prospective multi-institutional study of 1,028 consecutive patients with NMIBC undergoing CHT between 2012 and 2020. A total of 835 patients were treated with CHT with Mitomycin C (MMC). Disease was confirmed on transurethral resection of bladder tumor (TURBT) prior to starting CHT. Follow-up included cystoscopy and subsequent TURBT if recurrence/progression was suspected. The primary endpoint was RFS. Secondary endpoints were progression-free survival (PFS) and adverse events from CHT., Results and Limitations: Median follow up was 22.4 months (Interquartile range (IQR): 12.8 -35.8). Median age was 70.4 years (IQR: 62.1 -78.6). A total of 557 (66.7%), 172 (20.6) and 74 (8.9%) of patients were classified to BCG naïve, BCG unresponsive and BCG failure, respectively. The RFS at 12 months and 24 months for BCG naïve was 87.6% (95% CI 85.0% - 90.4%) and 75.0% (95% CI 71.3% - 78.8%), respectively. The RFS at 12 months and 24 months for BCG unresponsive cohort was 78.1% (95% CI 72.0% - 84.7%) and 57.4% (95% CI 49.7% - 66.3%), respectively. The RFS at 24 months for the BCG unresponsive cohort for CIS with/without papillary disease and papillary only disease were 43.6% (95% CI 31.4% -60.4%) and 64.5% (95% CI 55.4% - 75.1%), respectively. Minor adverse events occurred in 216 (25.6%) patients and severe events occurred in 17 (2.0%) patients., Conclusions: CHT with MMC using the Combat BRS is effective in the medium term and has a favorable adverse event profile., Competing Interests: Daniel A. González-Padilla has received payment for trial collaboration from Combat Medical. Félix Guerrero Ramos is a consultant and speaker for Combat Medical. Wei Shen Tan is a consultant to Combat Medical. Joan Palou Redorta is an Editorial Board member of this journal, but was not involved in the peer-review process nor had access to any information regarding its peer-review. Wei Phin Tan, Ana Plata Bello, Carlos Garcia Alvarez, Cajetan Nzeh, Jose Manuel de la Morena, Ignacio Gonzalez Valcarcel de Torres, Kees Hendricksen, Francisco Javier Díaz Goizueta, Fernandez J. Del Alamo, Francesco Chiancone, Paolo Fedelini, Massimiliano Poggio, Francesco Porpiglia, Victoria C. Gonzalo Rodríguez, Javier Montero Torres, Daniel Wilby, Richard Robinson, Alejandro Sousa-Escandón, Juan León Mata, Jose L. Pontones Moreno, Francisco Delgado Molina, Miguel A. Adriazola Semino, Andrew Townsley Stemberger and Jesús Calleja-Escudero declare no conflicts of interest., (© 2022 – The authors. Published by IOS Press.)

Objectives: To investigate the oncologic outcomes of pT0 after robot-assisted radical cystectomy (RARC)., Methods: A retrospective review of the International Robotic Cystectomy Consortium database was performed. Patients with pT0 after RARC were identified and analyzed. Data were reviewed for demographics and pathologic outcomes. Kaplan-Meier curves were used to depict recurrence-free survival (RFS), disease-specific survival (DSS), and overall survival (OS). Multivariate stepwise Cox regression models were used to identify variables associated with RFS and OS., Results: Four hundred seventy-one patients (18%) with pT0 were identified. Median age was 68 years (interquartile range (IQR) 60-73), with a median follow up of 20 months (IQR 6-47). Thirty-seven percent received neoadjuvant chemotherapy and 5% had pN+ disease. Seven percent of patients experienced disease relapse; 3% had local and 5% had distant recurrence. Most common sites of local and distant recurrences were pelvis (1%) and lungs (2%). Five-year RFS, DSS, and OS were 88%, 93%, and 79%, respectively. Age (hazards ratio [HR] 1.05, 95% confidence interval [CI] 1.01-1.09, P = 0.02), pN+ve (HR 11.48, 95% CI 4.47-29.49, P < .01), and reoperations within 30 days (HR 5.53, 95% CI 2.08-14.64, P < .01) were associated with RFS. Chronic kidney disease (HR 3.24, 95% CI 1.45-7.23, P < .01), neoadjuvant chemotherapy (HR 0.41, 95% CI 0.18-0.92, P = .03), pN+ve (HR 4.37, 95% CI 1.46-13.06, P < .01), and reoperations within 30 days (HR 2.64, 95% CI, 1.08-6.43, P = .03) were associated with OS., Conclusions: Despite pT0 status at RARC, 5% had pN+ disease and 7% of patients relapsed. Node status was the variable strongest associated with RFS and OS in pT0., (Copyright © 2022. Published by Elsevier Inc.)

Introduction: Appropriate risk stratification and complete tumor ablation are the key factors to optimize the oncologic outcomes of patients undertaking endoscopic management for upper urinary tract urothelial carcinoma (UTUC). We aimed to identify risk factors associated to tumor recurrence and progression in a contemporary cohort of patients diagnosed and treated with the latest endourologic technologies. Patients and Methods: Forty-seven patients were selected between January-2015 and March-2019 for an endoscopic management of UTUC. Last generation of digital ureteroscopes with image-enhancing technologies were used for the detection of the lesions. The retrograde approach was the most frequent access ( n  = 45/47). The confocal laser endomicroscopy and multiple biopsy devices were variably used according to site and tumor presentation for their characterization. Holmium and Thulium lasers were variably used, with their combination being the preferred approach in case of larger lesions. Primary endpoints included the identification of factors associated with UTUC recurrence and progression, and bladder tumor recurrence. Results: Median follow-up (FU) was 24 months (interquartile range 17-44). On multivariate analysis, bladder cancer (BC) recurrence was associated to previous contralateral UTUC (hazard ratios: 5.08 confidence interval [95% CI: 1.35-18.94], p  < 0.05) and tumor size (hazard ratios: 1.07 [95% CI: 1.00-1.14], p  < 0.05). UTUC recurrence was associated to incomplete clearance after primary treatment (hazard ratios: 4.99 [95% CI: 1.15-21.62], p  < 0.05), while UTUC progression was significantly related to the number of UTUC recurrences (hazard ratios: 3.10 [95% CI: 1.27-7.53], p  < 0.05). No significant survival differences in BC/UTUC recurrence, as well as in UTUC progression, were detected between risk groups. No Clavien-Dindo grade >2 were detected; one patient developed ureteric stricture at 7-month FU. Limitations involve retrospective nature of the study and relatively small number of patients. Conclusions: The appropriate use of latest technology may enhance the oncologic outcomes of the endoscopic management of UTUC without compromising the safety of the approach. Among the prognostic factors identified in our series, UTUC recurrence seems to be associated to disease progression.

Background: Unsteady camera movement and poor visualization contribute to a difficult learning curve for laparoscopic surgery. Remote-controlled camera holders (RCHs) aim to mitigate these factors and may be used to overcome barriers to learning. Our aim was to evaluate performance benefits to laparoscopic skill acquisition in novices using a RCH., Methods: Novices were randomized into groups using a human camera assistant (HCA) or the FreeHand v1.0 RCH and trained in the (E-BLUS) curriculum. After completing training, a surgical workload questionnaire (SURG-TLX) was issued to participants., Results: Forty volunteers naïve in laparoscopic skill were randomized into control and intervention groups (n = 20) with intention-to-treat analysis. Each participant received up to 10 training sessions using the E-BLUS curriculum. Competency was reached in the peg transfer task in 5.5 and 7.6 sessions for the ACH and HCA groups, respectively (P = 0.015), and 3.6 and 6.8 sessions for the laparoscopic suturing task (P = 0.0004). No significance differences were achieved in the circle cutting (P = 0.18) or needle guidance tasks (P = 0.32). The RCH group experienced significantly lower workload (P = 0.014) due to lower levels of distraction (P = 0.047)., Conclusions: Remote-controlled camera holders have demonstrated the potential to significantly benefit intra-operative performance and surgical experience where camera movement is minimal. Future high-quality studies are needed to evaluate RCHs in clinical practice., Trial Registration: ISRCTN 83733979.

Background: In patients with non-invasive urothelial carcinoma of the prostatic urethra (PUC), treatment with Bacillus Calmette-Guérin (BCG) could be beneficial., Objective: To assess the response rates to BCG in the different tumor stages, to describe the clinical impact of transurethral resection of the prostate (TURP) before BCG treatment, and to review the side effects of BCG treatment for PUC., Methods: A systematic search was conducted using the PubMed database to identify original studies between 1977 and 2019 reporting on PUC and BCG., Results: Of a total of 865 studies, ten were considered for evidence synthesis. An indication for BCG treatment was found in non-stromal invasive stages (Tis pu, Tis pd) and in stromal infiltrating cases (T1) of primary and secondary PUC when transitional cell carcinoma was the histology of origin. Studies including patients treated with TURP before BCG showed a better local response in the prostatic urethra with a higher disease free survival (DFS) (80-100% vs. 63-89%) and progression free survival (PFS) (90-100% vs. 75-94%) than patients in studies in which no TURP was performed. However, this difference in recurrence and progression in the prostate neither affected the total PFS (57-75% vs. 58-93%), nor the disease specific survival (70-100% vs. 66-100%)., Conclusions: The use of resection loop biopsies of the prostatic urethra in appropriate cases during the primary work-up for suspected PUC, as well as the use of the current TNM classification for PUC, need to be improved. BCG therapy for non-stromal invasive stages of PUC show a good local response. Local response is further improved by a TURP before BCG therapy, although the overall prognosis does not seem to be affected. Further evidence for BCG treatment in the rare cases of stromal invasive PUC is needed. Specific side effects of BCG treatment for PUC are not reported., Competing Interests: Georgios Gakis receives honoraria for advisory board activities: MSD, Astellas, Ferring, BMS, Bayer, Leo Pharma, medac, Merck, and he receives speaker honoraria/travel grants: Roche, MSD, IPSEN, Erbe, medac. Philippe E Spiess is the vice chair of the NCCN bladder and penile cancer panel; he is as well the president of the Global Society of Rare GU Tumors. Joan Palou Redorta reports trial participation: Cepheid, Presurgery, Ipsen, Combat, Storz, Archer, IDL Biotech, Palex and receives honoraria or consultation fees from Combat BRS, Olympus, Sanofi, Cepheid, Ipsen, Fidia Farmaceutici, and fees for Advisory/Scientific Board activities from: Pfizer, Astra Zeneca, Merck, Janssen, Ferring. Oliver Patschan and George N Thalmann have no conflict of interest to declare., (© 2021 – The authors. Published by IOS Press.)

Background: Radiation-induced cystitis is a common side effect of radiotherapy (RT) to the pelvic area. Hyaluronic acid (HA) and chondroitin sulfate (CS) are components of the urothelial mucosa and positive results have been obtained for intravesical HA/CS instillations for the treatment of urinary tract infections and bladder pain syndrome. HA/CS may also have a protective effect against RT bladder toxicity., Objective: To investigate whether HA and CS protect the urothelium during RT, alleviate lower urinary tract symptoms, and improve quality of life., Design Setting and Participants: This multicentre randomised controlled trial was conducted across seven centres in four countries. Male patients aged ≥18 yr scheduled to undergo primary intensity-modulated radiotherapy for localised prostate cancer were enrolled., Intervention: Patients were randomised to intravesical HA/CS plus an oral formulation of curcumin, quercetin, HA, and CS (group A) or no treatment (group B)., Outcome Measurements and Statistical Analysis: The primary endpoint was absolute changes from baseline to follow-up in urinary domain scores for the Expanded Prostate Cancer Index Composite (EPIC), the International Consultation on Incontinence Questionnaire-Male Lower Urinary Tract Symptoms (ICIQ-MLUTS), and the EuroQol Group EQ-5D-5L questionnaire. Data analysis for efficacy and safety outcomes was performed using an intention-to-treat (ITT) approach; the ITT population was defined as all randomised patients., Results and Limitations: Of 57 patients screened, 49 were enrolled and randomly assigned to either active treatment (group A, n  = 25) or the control (group B, n  = 24). Three patients in the control group withdrew after randomisation. Changes from baseline to 12 mo were worse in the control group for subtotal scores for urinary symptoms and impact of symptoms on quality of life and for the total score ( p  =  0.05, p  =  0.003, and p  =  0.008, respectively). There was a significant time × group interaction in favour of active treatment for the incontinence symptom score ( p  =  0.011) and bother score ( p  =  0.017). The absence of a sham procedure and/or placebo is the main limitation., Conclusions: Our results suggest that intravesical HA/CS in combination with an oral formulation may reduce urinary symptoms and improve QoL at short-term (1 yr) follow-up., Patient Summary: We investigated whether hyaluronic acid (HA) and chondroitin sulfate (CS) have a protective effect against the bladder toxicity of radiotherapy for prostate cancer. HA/CS used for weekly bladder irrigation for 6 wk and given orally with curcumin and quercetin for 12 wk reduced urinary incontinence symptoms and bother measured at 1-year follow-up. This may hold promise as a preventive treatment if the results are confirmed in further trials., (© 2021 The Authors.)

Purpose: Radical cystectomy is the gold standard for nonmetastatic muscle invasive bladder cancer and for refractory nonmuscle invasive disease. Compared to open radical cystectomy, robot-assisted radical cystectomy has been shown to provide comparable early oncologic outcomes and improved perioperative outcomes. However, there is a paucity of data on long-term oncologic outcomes and concerns about a higher incidence of local recurrence after robot-assisted radical cystectomy. We report 10-year oncologic outcomes following robot-assisted radical cystectomy using a multinational database., Materials and Methods: We retrospectively reviewed the prospective International Robotic Cystectomy Consortium database. Consecutive patients who underwent robot-assisted radical cystectomy 10 years ago or earlier were included in analysis. Data were reviewed for demographics, and perioperative, pathological and oncologic outcomes. Kaplan-Meier curves were used to depict recurrence-free, disease specific and overall survival. Multivariate stepwise Cox regression models were applied to identify variables associated with recurrence-free, disease specific and overall survival., Results: We identified 446 patients with a median age of 67 years (IQR 59-76). Of the patients 10% received neoadjuvant chemotherapy, 51% experienced any complication, 23% had high grade complications and 4% died within 3 months of robot-assisted radical cystectomy. Disease was pT3 or greater in 43% of patients and pN+ in 24% while a positive soft tissue surgical margin was observed in 7%. At a median followup of 5 years (IQR 2-10, maximum 14) local and distant recurrence had developed in 15% and 29% of patients, respectively. Ten-year recurrence-free, disease specific and overall survival rates were 59%, 65% and 35%, respectively. Patients with pT3 or greater and pN+ disease showed worse recurrence-free, disease specific and overall survival., Conclusions: Long-term oncologic outcomes, and recurrence rates and patterns after robot-assisted radical cystectomy seem comparable to those in open series. Advanced disease stage and positive surgical margins remain the main determinants of survival after radical cystectomy.

Purpose: To evaluate on a lesion-by-lesion basis Narrow-Band Imaging flexible videoscopy (NBI-FV) in the detection of cancer compared to White-Light Imaging flexible videoscopy (WLI-FV)., Methods: WLI-FV and NBI-FV were sequentially performed in patients scheduled for TURBT for primary bladder cancer. Suspicious findings were individually harvested and characterized under WLI-FV (suspicious/non-suspicious) and NBI-FV (5-point Likert scale) and pathology. The primary objective was to determine if NBI-FV informed at least 20% more cancer lesions than WLI-FV (Relative true-positive rate > 1.19). A minimum of 120 specimens was to be analyzed to reach 90% power., Results: Of 147 specimens taken in 68 patients, 101 were found suspicious under WLI-FV and 64 (64/101, 63.4%) confirmed as cancer. Of the 46 lesions undetected by WLI-VF, 16 were found positive for cancer (16/46, 34.8%). For NBI-FV, a significant increase in positive samples was observed with increments in Likert scale (p < 0.0002). Relative true-positive rate was 1.22 (95% CI 1.12-1.39)-NBI-FV detected 22% more cancer lesions compared to WLI-FV. Relative false-positive rate was 1.35 (95% CI 1.19-1.59)., Conclusion: Researching alterations in mucosa and microvasculature by narrow-band imaging flexible videoscopy augmented by 22% the detection of cancer foci and contributed to the objective of complete resection of all visible lesions. Conversely, it entailed a 35% increase in false-positive results compared to white-light imaging, although the structured analysis of narrow-band imaging findings might be used to grade suspicion according to the Likert scale and balance the risk of a false-positive result to the benefit of demonstrating cancer.

Background: Simulation-based training offers an acceptable adjunct to the traditional mentor-apprentice model in helping trainees to traverse the early stages of the learning curve for ureteroscopy and percutaneous renal surgery. In addition, nontechnical skills are increasingly important in preventing adverse events in the operating room, and simulation-based training can be used for training in such skills. Incorporation of simulation into formalised, standardised, and validated curricula offers an applicable method for training residents., Objective: To develop a curriculum for urolithiasis procedures incorporating technical and nontechnical skills training for implementation across Europe., Design, Setting, and Participants: An international panel of experts from EULIS, EUREP, ESU and ESUT was consulted in five stages. The study incorporated a mix of qualitative and quantitative data for collection and analysis. Responses were drawn out in (1) an opinion survey and (2) a curriculum development survey, which were discussed in (3) a focus group meeting. Group responses from this meeting were analysed for themes, which were discussed at (4) a focus group meeting, where consensus was reached among the group. Data analysis and integration at this stage were used to draft the curriculum., Results and Limitations: All group meetings were transcribed from the focus group discussion. Eight themes were generated, into which all data were categorised. These were: need for a training curriculum; curriculum objectives; curriculum structure; curriculum content; teaching platforms and tools; assessment and certification; validation and implementation; and global integration of the curriculum. A curriculum, including recommended simulators for use, was subsequently proposed., Conclusions: We propose a comprehensive curriculum for training in urolithiasis. Additional planning is required for full validation and implementation before it can be used to train residents., Patient Summary: Stone disease accounts for a major proportion of surgical interventions worldwide. We describe a consensus guideline for effective training of stone surgeons., (Copyright © 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Objectives: The treatment of non muscle invasive bladder cancer (NMIBC) continues to be a challenge. Hyperthermia (HT) combined with intravesical chemotherapy is used to enhance the effects of chemotherapy., Methods: A review of the publications was carried out to synthesize the adverse effects (AE) reported by the use of chemohyperthermia (QHT) with Mitomycin-C (MMC). The most relevant data are exposed for each of the devices currently used in the QHT., Results: SYNERGO®: The dropout rate varied between 3-40%, and the AE rate is up to 88%. The most common AEs were pain (2-40%), thermal reaction of the posterior wall (13-100%), bladder spasms (2-32%), dysuria (3-60%) and hematuria (2-62%). COMBAT BRS®: The dropout rate is 3-11%. The AEs reported were CTCAE Grade 1-2: Pain 13-27%, bladder spasms 6-27%and hematuria 3-20% are the most relevant. In general, CTCAE grade 3-4 toxicity is not reported. UNITHERMIA®: The dropout rate is 7-12%. The AEs described are: Pain 6-23%, bladder spasms 6-23%, hematuria 9-11, frequency 15-25% and allergy 6-11%. The majority of toxicities are CTCAE grade 1-2 (17-53%), with grade 3-4 in 9-15% and Grade 5 in 0-2%. QHT adds little to the AEs of the treatment with MMC. It neither adds severe effects, nor increases dropouts significantly, and does not increase the incidence of allergic reactions. The comparative study between BCG and QHT-MMC, is less likely to present urinary frequency, nocturia, incontinence, hematuria, fever, fatigue and arthralgia in patients in the QHT group., Conclusions: QHT has proven to be a safe alternative for the treatment of intermediate and high risk NMIBC, with AE mainly grade 1-2. The AEs reported have little variation with respect to the dose of MMC used, presenting different "profiles" related to the device used for its administration. The treatments with QHTMMC are well tolerated, without adding significantly more AE than the instillations of MMC alone and presenting a better toxicity profile than those reflected in the literature with respect to the treatment with BCG.

Objectives: To design a methodology to predict operative times for robot-assisted radical cystectomy (RARC) based on variation in institutional, patient, and disease characteristics to help in operating room scheduling and quality control., Patients and Methods: The model included preoperative variables and therefore can be used for prediction of surgical times: institutional volume, age, gender, body mass index, American Society of Anesthesiologists score, history of prior surgery and radiation, clinical stage, neoadjuvant chemotherapy, type, technique of diversion, and the extent of lymph node dissection. A conditional inference tree method was used to fit a binary decision tree predicting operative time. Permutation tests were performed to determine the variables having the strongest association with surgical time. The data were split at the value of this variable resulting in the largest difference in means for the surgical time across the split. This process was repeated recursively on the resultant data sets until the permutation tests showed no significant association with operative time., Results: In all, 2 134 procedures were included. The variable most strongly associated with surgical time was type of diversion, with ileal conduits being 70 min shorter (P < 0.001). Amongst patients who received neobladders, the type of lymph node dissection was also strongly associated with surgical time. Amongst ileal conduit patients, institutional surgeon volume (>66 RARCs) was important, with those with a higher volume being 55 min shorter (P < 0.001). The regression tree output was in the form of box plots that show the median and ranges of surgical times according to the patient, disease, and institutional characteristics., Conclusion: We developed a method to estimate operative times for RARC based on patient, disease, and institutional metrics that can help operating room scheduling for RARC., (© 2017 The Authors BJU International © 2017 BJU International Published by John Wiley & Sons Ltd.)

Purpose: We sought to investigate the prevalence and variables associated with early oncologic failure., Materials and Methods: We retrospectively reviewed the IRCC (International Radical Cystectomy Consortium) database of patients who underwent robot-assisted radical cystectomy since 2003. The final cohort comprised a total of 1,894 patients from 23 institutions in 11 countries. Early oncologic failure was defined as any disease relapse within 3 months of robot-assisted radical cystectomy. All institutions were surveyed for the pneumoperitoneum pressure used, breach of oncologic surgical principles, and techniques of specimen and lymph node removal. A multivariate model was fit to evaluate predictors of early oncologic failure. The Kaplan-Meier method was applied to depict disease specific and overall survival, and Cox proportional regression analysis was used to evaluate predictors of disease specific and overall survival., Results: A total of 305 patients (22%) experienced disease relapse, which was distant in 220 (16%), local recurrence in 154 (11%), peritoneal carcinomatosis in 17 (1%) and port site recurrence in 5 (0.4%). Early oncologic failure developed in 71 patients (5%) at a total of 10 institutions. The incidence of early oncologic failure decreased from 10% in 2006 to 6% in 2015. On multivariate analysis the presence of any complication (OR 2.87, 95% CI 1.38-5.96, p = 0.004), pT3 or greater disease (OR 3.73, 95% CI 2.00-6.97, p <0.001) and nodal involvement (OR 2.14, 95% CI 1.21-3.80, p = 0.008) was a significant predictor of early oncologic failure. Patients with early oncologic failure demonstrated worse disease specific and overall survival (23% and 13%, respectively) at 1 and 3 years compared to patients who experienced later or no recurrences (log rank p <0.001)., Conclusions: The incidence of early oncologic failure following robot-assisted radical cystectomy has decreased with time. Disease related rather than technical related factors have a major role in early oncologic failure after robot-assisted radical cystectomy., (Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Evidence regarding the diagnostic accuracy of a [-2]proPSA derivative, namely, the prostate health index (PHI), to predict the presence of prostate cancer (PCa) in individuals with high total prostate-specific antigen (tPSA) levels is lacking. We tested the hypothesis that these markers could assist clinicians in the biopsy decision path of patients with tPSA>10ng/ml., Methods: The primary endpoint was to evaluate the sensitivity, specificity, and diagnostic accuracy of PHI in determining the presence of PCa at biopsy in comparison to tPSA, free PSA, and % of free to total PSA. We calculated the number of prostate biopsies that could have been spared by using this marker to decide whether or not to perform a biopsy. A secondary endpoint was to determine the relationship between PHI and PCa characteristics., Results: The PCa was diagnosed in 136 of 262 patients (51.9%). Total PSA and PHI values were significantly higher (P<0.005) and % of free to total PSA values significantly lower (P<0.0001) in patients with PCa relative to those with a negative biopsy. In multivariable logistic regression models, PHI achieved the independent predictor status and significantly increased the accuracy of the base multivariable model by an extent of 8.2% (P = 0.0005). The inclusion of PHI in the biopsy decision path would decrease the number of unnecessary biopsies by an extent of 50.0%, while missing only few cases with clinically significant PCa. Finally, Gleason score was significantly related to PHI levels., Conclusions: The results of our study support the diagnostic effectiveness of PHI even in patients with tPSA >10ng/ml. Further validation studies with larger sample size are needed to corroborate our findings., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objectives: To test the hypothesis that [-2]proPSA (p2PSA) and its derivatives are more accurate than total prostate-specific antigen (tPSA), free prostate-specific antigen (fPSA) and fPSA as percentage of tPSA (%fPSA) in detecting prostate cancer (PCa) in men aged <60 years., Patients and Methods: The analysis consisted of a nested case-control study from the PRO- PSA Multicentric European Study (PROMEtheuS) project. The primary outcomes were measures of sensibility, specificity and accuracy of serum p2PSA, p2PSA as percentage of fPSA (%p2PSA) and Beckman Coulter prostate health index (PHI) in men aged <60 years who had undergone a prostate biopsy. The potential reduction in the number of unnecessary biopsies and the characteristics of the potentially missed PCa cases were reported as secondary outcomes. Multivariate logistic regression models were complemented by predictive accuracy and decision-curve analyses., Results: Of the 1036 patients enrolled in the PROMEtheus project, 238 (22.9%) were aged < 60 years. PCa was found in 67 subjects (28.1%); p2PSA, %p2PSA and PHI values were significantly higher (P < 0.001) among these subjects, while no differences were found in tPSA, fPSA and %fPSA values. On univariate analysis, %p2PSA (area under the curve [AUC]: 0.704) and PHI (AUC: 0.7) were the most accurate predictors, and these significantly outperformed tPSA (AUC: 0.549), fPSA (AUC: 0.511) and %fPSA (AUC: 0.557) in the prediction of PCa at biopsy (P ≤ 0.001). In multivariate logistic regression models, %p2PSA and PHI achieved independent predictor status and significantly increased the accuracy of multivariate models by 6.3 and 7.6%, respectively (P ≤ 0.05)., Conclusion: PHI and %p2PSA are more accurate than the reference standard tests in predicting PCa in young men., (© 2014 The Authors. BJU International © 2014 BJU International.)

Objectives: To test serum prostate-specific antigen (PSA) isoform [-2]proPSA (p2PSA), p2PSA/free PSA (%p2PSA) and Prostate Health Index (PHI) accuracy in predicting prostate cancer in obese men and to test whether PHI is more accurate than PSA in predicting prostate cancer in obese patients., Patients and Methods: The analysis consisted of a nested case-control study from the pro-PSA Multicentric European Study (PROMEtheuS) project. The study is registered at http://www.controlled-trials.com/ISRCTN04707454. The primary outcome was to test sensitivity, specificity and accuracy (clinical validity) of serum p2PSA, %p2PSA and PHI, in determining prostate cancer at prostate biopsy in obese men [body mass index (BMI) ≥30 kg/m(2) ], compared with total PSA (tPSA), free PSA (fPSA) and fPSA/tPSA ratio (%fPSA). The number of avoidable prostate biopsies (clinical utility) was also assessed. Multivariable logistic regression models were complemented by predictive accuracy analysis and decision-curve analysis., Results: Of the 965 patients, 383 (39.7%) were normal weight (BMI <25 kg/m(2) ), 440 (45.6%) were overweight (BMI 25-29.9 kg/m(2) ) and 142 (14.7%) were obese (BMI ≥30 kg/m(2) ). Among obese patients, prostate cancer was found in 65 patients (45.8%), with a higher percentage of Gleason score ≥7 diseases (67.7%). PSA, p2PSA, %p2PSA and PHI were significantly higher, and %fPSA significantly lower in patients with prostate cancer (P < 0.001). In multivariable logistic regression models, PHI significantly increased accuracy of the base multivariable model by 8.8% (P = 0.007). At a PHI threshold of 35.7, 46 (32.4%) biopsies could have been avoided., Conclusion: In obese patients, PHI is significantly more accurate than current tests in predicting prostate cancer., (© 2014 The Authors. BJU International © 2014 BJU International.)

Robot-assisted radical cystectomy (RARC) is an emerging operative alternative to open surgery for the management of invasive bladder cancer. Studies from single institutions provide limited data due to the small number of patients. In order to better understand the related outcomes, a world-wide consortium was established in 2006 of patients undergoing RARC, called the International Robotic Cystectomy Consortium (IRCC). Thus far, the IRCC has reported its findings on various areas of operative interest and continues to expand its capacity to include other operative modalities and transform it into the International Radical Cystectomy Consortium. This article summarizes the findings of the IRCC and highlights the future direction of the consortium.

Background: Intracorporeal urinary diversion (ICUD) has the potential benefits of a smaller incision, reduced pain, decreased bowel exposure, and reduced risk of fluid imbalance., Objective: To compare the perioperative outcomes of patients undergoing extracorporeal urinary diversion (ECUD) and ICUD following robot-assisted radical cystectomy (RARC)., Design, Setting, and Participants: We reviewed the database of the International Robotic Cystectomy Consortium (IRCC) (18 international centers), with 935 patients who had undergone RARC and pelvic lymph node dissection (PLND) between 2003 and 2011., Intervention: All patients within the IRCC underwent RARC and PLND as indicated. The urinary diversion was performed either intracorporeally or extracorporeally., Outcome Measurements and Statistical Analysis: Demographic data, perioperative outcomes, and complications in patients undergoing ICUD or ECUD were compared. All patients had at least a 90-d follow-up. The Fisher exact test was used to summarize categorical variables and the Wilcoxon rank sum test or Kruskal-Wallis test for continuous variables., Results and Limitations: Of 935 patients who had RARC and PLND, 167 patients underwent ICUD (ileal conduit: 106; neobladder: 61), and 768 patients had an ECUD (ileal conduit: 570; neobladder: 198). Postoperative complications data were available for 817 patients, with a minimum follow-up of 90 d. There was no difference in age, gender, body mass index, American Society of Anesthesiologists grade, or rate of prior abdominal surgery between the groups. The operative time was equivalent (414 min), with the median hospital stay being marginally longer for the ICUD group (9 d vs 8 d, p=0.086). No difference in the reoperation rates at 30 d was noted between the groups. The 90-d complication rate was not significant between the two groups, but a trend favoring ICUD over ECUD was noted (41% vs 49%, p=0.05). Gastrointestinal complications were significantly lower in the ICUD group (p ≤ 0.001). Patients with ICUD were at a lower risk of experiencing a postoperative complication at 90 d (32%) (odds ratio: 0.68; 95% confidence interval, 0.50-0.94; p=0.02). Being a retrospective study was the main limitation., Conclusions: Robot-assisted ICUD can be accomplished safely, with comparable outcomes to open urinary diversion. In this cohort, patients undergoing ICUD had a relatively lower risk of complications., (Copyright © 2013. Published by Elsevier B.V.)

Objectives: To test the sensitivity, specificity and accuracy of serum prostate-specific antigen isoform [-2]proPSA (p2PSA), %p2PSA and the prostate health index (PHI), in men with a family history of prostate cancer (PCa) undergoing prostate biopsy for suspected PCa. To evaluate the potential reduction in unnecessary biopsies and the characteristics of potentially missed cases of PCa that would result from using serum p2PSA, %p2PSA and PHI., Patients and Methods: The analysis consisted of a nested case-control study from the PRO-PSA Multicentric European Study, the PROMEtheuS project. All patients had a first-degree relative (father, brother, son) with PCa. Multivariable logistic regression models were complemented by predictive accuracy analysis and decision-curve analysis., Results: Of the 1026 patients included in the PROMEtheuS cohort, 158 (15.4%) had a first-degree relative with PCa. p2PSA, %p2PSA and PHI values were significantly higher (P < 0.001), and free/total PSA (%fPSA) values significantly lower (P < 0.001) in the 71 patients with PCa (44.9%) than in patients without PCa. Univariable accuracy analysis showed %p2PSA (area under the receiver-operating characteristic curve [AUC]: 0.733) and PHI (AUC: 0.733) to be the most accurate predictors of PCa at biopsy, significantly outperforming total PSA ([tPSA] AUC: 0.549), free PSA ([fPSA] AUC: 0.489) and %fPSA (AUC: 0.600) (P ≤ 0.001). For %p2PSA a threshold of 1.66 was found to have the best balance between sensitivity and specificity (70.4 and 70.1%; 95% confidence interval [CI]: 58.4-80.7 and 59.4-79.5 respectively). A PHI threshold of 40 was found to have the best balance between sensitivity and specificity (64.8 and 71.3%, respectively; 95% CI 52.5-75.8 and 60.6-80.5). At 90% sensitivity, the thresholds for %p2PSA and PHI were 1.20 and 25.5, with a specificity of 37.9 and 25.5%, respectively. At a %p2PSA threshold of 1.20, a total of 39 (24.8%) biopsies could have been avoided, but two cancers with a Gleason score (GS) of 7 would have been missed. At a PHI threshold of 25.5 a total of 27 (17.2%) biopsies could have been avoided and two (3.8%) cancers with a GS of 7 would have been missed. In multivariable logistic regression models, %p2PSA and PHI achieved independent predictor status and significantly increased the accuracy of multivariable models including PSA and prostate volume by 8.7 and 10%, respectively (P ≤ 0.001). p2PSA, %p2PSA and PHI were directly correlated with Gleason score (ρ: 0.247, P = 0.038; ρ: 0.366, P = 0.002; ρ: 0.464, P < 0.001, respectively)., Conclusions: %p2PSA and PHI are more accurate than tPSA, fPSA and %fPSA in predicting PCa in men with a family history of PCa. Consideration of %p2PSA and PHI results in the avoidance of several unnecessary biopsies. p2PSA, %p2PSA and PHI correlate with cancer aggressiveness., (© 2013 BJU International.)

Context: Minimally invasive radical cystectomy (MIRC) techniques for the treatment of muscle-invasive bladder cancer (BCa) are being increasingly applied. MIRC offers the potential benefits of a minimally invasive approach in terms of reduced blood loss and analgesic requirements whilst striving to provide similar oncologic efficacy to open radical cystectomy (ORC). Whether quicker recovery, shorter hospital stay, and a reduction in complications are routinely achieved with MIRC remains to be proved in prospective comparisons., Objective: To explore both laparoscopic radical cystectomy (LRC) and robot-assisted radical cystectomy (RRC), focusing specifically on the oncologic parameters and comorbidity of the procedures. Reported complications from major centres are identified and categorised via the Clavien system. Positive margins rates, local recurrence, and both cancer-specific survival (CSS) and overall survival rates are assessed., Evidence Acquisition: A comprehensive electronic literature search was conducted in November 2010 using the Medline database to identify publications relating to laparoscopic, robotic, or minimally invasive radical cystectomy., Evidence Synthesis: There are encouraging short- to medium-term results for both LRC and RRC in terms of postoperative morbidity and oncologic outcomes. It seems possible in experienced hands to perform a satisfactory minimally invasive lymphadenectomy regarding lymph node counts and levels of dissection. Positive soft-tissue margins are similar to large open series for T2/T3 disease but inferior for bulky T4 disease. Local recurrence rates and CSS rates seem equivalent to ORC at up to 3 yr of follow-up; however, mature outcome data still need to be presented before definitive comparisons can be made., Conclusions: Robotic and laparoscopic cystectomy has a growing role in the management of muscle-invasive BCa. Long-term oncologic results are awaited, and there are concerns over the ability of MIRC to treat bulky and locally advanced disease, making careful patient selection vital. Forthcoming randomised trials in this area will more fully address these issues., (Copyright © 2011 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Context: Compared with standard white-light cystoscopy, photodynamic diagnosis with blue light and the photosensitiser hexaminolevulinate has been shown to improve the visualisation of bladder tumours, reduce residual tumour rates by at least 20%, and improve recurrence-free survival. There is currently no overall European consensus outlining specifically where hexaminolevulinate is or is not indicated., Objective: Our aim was to define specific indications for hexaminolevulinate-guided fluorescence cystoscopy in the diagnosis and management of non-muscle-invasive bladder cancer (NMIBC)., Evidence Acquisition: A European expert panel was convened to review the evidence for hexaminolevulinate-guided fluorescence cystoscopy in the diagnosis and management of NMIBC (identified through a PubMed MESH search) and available guidelines from across Europe. On the basis of this information and drawing on the extensive clinical experience of the panel, specific indications for the technique were then identified through discussion., Evidence Synthesis: The panel recommends that hexaminolevulinate-guided fluorescence cystoscopy be used to aid diagnosis at initial transurethral resection following suspicion of bladder cancer and in patients with positive urine cytology but negative white-light cystoscopy for the assessment of tumour recurrences in patients not previously assessed with hexaminolevulinate, in the initial follow-up of patients with carcinoma in situ (CIS) or multifocal tumours, and as a teaching tool. The panel does not currently recommend the use of hexaminolevulinate-guided fluorescence cystoscopy in patients for whom cystectomy is indicated or for use in the outpatient setting with flexible cystoscopy., Conclusions: Evidence is available to support the use of hexaminolevulinate-guided fluorescence cystoscopy in a range of indications, as endorsed by an expert panel., (Copyright © 2010 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Urethral cancer is an infrequent pathology, less than 1% of the genitourinary tumors. It is more frequent in women (4:1), in the sixth or seventh decade of life. The most frequent histology being squamous cell carcinoma. First signs and symptoms usually are more attributable to benign stricture disease, rather than malignicy. The interval between the onset of symptoms and diagnosis may be as long as three years. Therefore most of these tumors are locally advanced at the time of diagnosis with generally poor prognosis despite aggressive treatment. Therapeutic management varies with the stage and location of the lesion. Because of the rarity of this pathology, no consensus has been reached on treatment modalities, but seems to be that must be a multimodal one, including surgery, radiotherapy and chemotherapy. We present the case of an 80 year-old male, with a diagnosis of urethral squamous-cell cancer, locally advanced at the time of diagnosis. Surgery was not feasible. The patient underwent chemotherapy and radiotherapy with evidence of quick progression thereafter.

More than 100 million people worldwide are affected by bilharziasis, caused by Schistosoma haematobium. For travellers precaution is most important. For the population in endemic areas, an integrated approach including health education is necessary. Effective pharmacologic treatment is available.

Nearly one third of the world's population is estimated to be infected with Mycobacterium tuberculosis. Moreover, tuberculosis is the most common opportunistic infection in AIDS patients. Genitourinary tuberculosis is not very common but it is considered as a severe form of extra-pulmonary tuberculosis The diagnosis of genitourinary tuberculosis is made based on culture studies by isolation of the causative organism; however, biopsy material on conventional solid media may occasionally be required. Drug treatment is the first line therapy in genitourinary tuberculosis. Treatment regimens of 6 months are effective in most of the patients. Although chemotherapy is the mainstay of treatment, surgery in the form of ablation or reconstruction may be unavoidable. Both radical and reconstructive surgery should be carried out in the first 2 months of intensive chemotherapy.