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Objectives: We sought to determine whether bladder cuff excision and its technique influence outcomes after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC)., Methods and Materials: A multicenter, international, retrospective analysis using the ROBotic surgery for Upper tract Urothelial cancer Study (ROBUUST) 2.0 registry identified 1,718 patients undergoing RNU for UTUC between 2015 and 2023 at 17 centers across the United States, Europe, and Asia. Data was gathered on (1) whether bladder cuff excision was performed and (2) what technique was used, including formal excision or other techniques (pluck technique, stripping/intussusception technique) and outcomes. Multivariate and survival analyses were performed to compare the groups., Results: Most patients (90%, 1,540/1,718) underwent formal bladder cuff excision in accordance with EAU and AUA guidelines. Only 4% (68/1,718) underwent resection using other techniques, and 6% (110/1,718) did not have a bladder cuff excised. Median follow up for the cohort was 24 months (IQR 9-44). When comparing formal bladder cuff excision to other excision techniques, there were no differences in oncologic or survival outcomes including bladder recurrence-free survival (BRFS), recurrence-free survival (RFS), metastasis-free survival (MFS), overall survival (OS), or cancer-specific survival (CSS). However, excision of any kind conferred a decreased risk of bladder-specific recurrence compared to no excision. There was no difference in RFS, MFS, OS, or CSS when comparing bladder cuff excision, other techniques, and no excision., Conclusions: Bladder cuff excision improves recurrence-free survival, particularly when considering bladder recurrence. This benefit is conferred regardless of technique, as long as the intramural ureter and ureteral orifice are excised. However, the benefit of bladder cuff excision on metastasis-free, overall, and cancer-specific survival is unclear., 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 © 2024 Elsevier Inc. All rights reserved.)

Objective: Discrepancies in survival outcomes of various genitourinary tract malignancies have been documented across different racial and ethnic groups. Here we sought to examine long-term survival outcomes of patients with upper tract urothelial carcinoma (UTUC) following radical nephroureterectomy (RNU) when stratified by race., Methods: A multicenter retrospective analysis using the ROBUUST (ROBotic surgery for Upper tract Urothelial cancer Study) registry identified patients undergoing RNU for UTUC between 2015 and 2022 at 12 centers across the United States, Europe, and Asia. Patients were stratified by race (white, black, Hispanic, and Asian) and primary outcomes of interest-including recurrence-free survival (RFS), metastasis free survival (MFS) and overall survival (OS) - were assessed using univariate analysis, multivariate Cox regression modeling, and Kaplan-Meier analysis., Results: 1446 patients (white n = 652, black n = 70, Hispanic n = 87, and Asian n = 637) who underwent RNU for treatment of the UTUC were included in our analysis. Cox regression modeling demonstrated pathologic nodal staging to be a significant predictor of RFS (HR 2.25; P = .0010), MFS (HR 2.50; P = .0028), and OS (HR 5.11; P < .0001). When using whites as the reference group, there were no significant differences in RFS, MFS, or OS across racial groups., Conclusions: Unlike other genitourinary tract malignancies, our study failed to demonstrate a survival disadvantage among minority racial groups with UTUC who underwent RNU. Furthermore, a significant difference in RFS, MFS, and OS was not identified across whites, blacks, Asians, or Hispanics with UTUC who underwent RNU., Competing Interests: Disclosure The authors have stated that they have no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: To assess the efficacy and safety of combined High-Intensity Focused Ultrasound (HIFU) and Holmium Laser Enucleation of the Prostate (HoLEP) in treating patients with both localized prostate cancer (PCa) and prostate > 60 g., Methods: All patients who underwent HIFU for treatment of localized PCa were prospectively enrolled in our study. We reviewed records of patients undergoing procedures from January 2016 to January 2023. For patients with prostate sizes > 60 g, HoLEP was offered before HIFU to prevent worsened urinary symptoms post-treatment. Oncological outcomes-prostatic-specific (PSA) kinetics, recurrence rates, treatment failure - and functional results-Sexual Health Inventory for Men (SHIM), International Prostate Symptoms Score (IPSS), and urinary complications were compared between patients undergoing combined HoLEP and HIFU with those underwent HIFU-monotherapy., Results: Among 100 patients, 74 underwent HIFU-monotherapy and 26 underwent the combined HoLEP and HIFU. The majority had intermediate-risk PCa (67%). Pathologic assessment of HoLEP specimens showed no tumor evidence in 57% of cases. In comparison to the HIFU-only group, the combined group exhibited significantly lower PSA metrics across various intervals, however, no differences were found regarding overall and infield recurrences and treatment failure rates. While the combined treatment initially resulted in higher incontinence rates and shorter catheterization durations (P < 0.001), no significant difference in IPSS was observed during subsequent follow-ups., Conclusion: HoLEP and HIFU can be safely combined for the treatment of PCa in patients with >60 g prostate volume without compromising early oncological outcomes thereby expanding the therapeutic scope of HIFU in treating patients with localized PCa and large adenomas., 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 © 2024 Elsevier Inc. All rights reserved.)

Background: Diagnostic ureteroscopy (URS) with or without biopsy remains a subject of contention in the management of upper tract urothelial carcinoma (UTUC), with varying recommendations across different guidelines. The study aims to analyse the decision-making and prognostic role of diagnostic ureteroscopy (URS) in high-risk UTUC patients undergoing curative surgery., Materials and Methods: In this retrospective multi-institutional analysis of high-risk UTUC patients from the ROBUUST dataset, a comparison between patients who received or not preoperative URS and biopsy before curative surgery was carried out. Logistic regression analysis evaluated differences between patients receiving URS and its impact on treatment strategy. Survival analysis included 5-year recurrence-free survival (RFS), metastasis-free survival (MFS), cancer-specific survival (CSS) and overall survival (OS). After adjusting for high-risk prognostic group features, Cox proportional hazard model estimated significant predictors of time-to-event outcomes., Results: Overall, 1,912 patients were included, 1,035 with preoperative URS and biopsy and 877 without. Median follow-up: 24 months. Robot-assisted radical nephroureterectomy was the most common procedure (55.1%), in both subgroups. The 5-year OS (P = 0.04) and CSS (P < 0.001) were significantly higher for patients undergoing URS. The 5-year RFS (P = 0.6), and MFS (P = 0.3) were comparable between the 2 groups. Preoperative URS and biopsy were neither a significant predictor of worse oncological outcomes nor of a specific treatment modality., Conclusions: The advantage in terms of OS and CSS in patients undergoing preoperative URS could derive from a better selection of candidates for curative treatment. The treatment strategy is likely more influenced by tumor features than by URS findings., 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 © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: To identify whether there was a disparity in the utilization of immunotherapy in the treatment of black patients with metastatic castration resistant prostate cancer (mCRPC)., Methods: Using the National Cancer Database, we identified patients between 2010- 2015 with likely minimally/asymptomatic mCRPC. We analyzed annual trends for chemotherapy and immunotherapy use and compared utilization by demographic and clinical features. Multivariable analysis was performed to determine predictors of receiving immunotherapy vs chemotherapy., Results: We identified 1301 patients with likely mCRPC. The majority were non Hispanic White (NHW - 63 %) and 23 % were non-Hispanic Black (NHB). Overall, there was increased utilization of immunotherapy in mCRPC from 2010 onwards, with the peak occurring in 2014 (4.6 %). Chemotherapy use increased significantly, peaking in 2014 to 26.1 %. However, the increased utilization of immunotherapy in the mCRPC was mainly seen in White patients: from 50 % to 74.2 % of the cohort. Conversely, there was a decrease in utilization of immunotherapy among Black mCPRC patients: from 50 % to 25.8 %. On multivariable analysis, there was no statistically significant difference between treatment types by race., Conclusion: FDA approval of Sipuleucel-T for mCRPC led to increased utilization of immunotherapy shortly thereafter, but this was mainly noted in white patients. Black patients comparatively did not exhibit increased utilization of this novel agent after 2010. Further studies are necessary to help understand barriers to access to new treatment in mCRPC and eliminate the burden of disease in minority populations.", Competing Interests: Declaration of Competing Interest The authors have no competing interests to declare that are relevant to the content of this article., (Copyright © 2023 National Medical Association. Published by Elsevier Inc. All rights reserved.)

Objective: To investigate clinical risk factors associated with postoperative deep incisional or organ/space surgical site infections (SSI) following radical cystectomy (RC) in a well characterized and large contemporary cohort., Methods: We used the American College of Surgeons National Surgical Quality Improvement Program database to identify adult patients who underwent RC for bladder cancer between 2015 and 2020 (n = 13,081). We conducted multivariable-adjusted logistic regression and Cox adjusted proportional hazards regression analysis to identify clinical predictors of deep incisional or organ/space SSI in the 30-day postoperative-period following RC., Results: Deep incisional or organ/space SSI risk increased with continent urinary diversion (HR = 1.61, 95% CI: 1.38-1.88; P < 0.001), obesity (HR = 1.60, 95% CI: 1.35-1.90; P < 0.001), diabetes mellitus (HR = 1.30, 95% CI: 1.13-1.51; P < 0.001), and being functionally dependent before surgery (HR = 2.09, 95% CI: 1.44-3.03; P < 0.001)., Conclusions: Postoperative deep incisional or organ/space SSIs following RC occur more frequently in patients who were obese, diabetic, functionally dependent before surgery, and those who underwent continent urinary diversion. These findings may assist urologists in preoperative counseling, medical optimization, and choice of urinary diversion approach, as well as improved patient monitoring and identification of candidates for intervention postoperatively., 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 Elsevier Inc. All rights reserved.)

Introduction: Oncologic implications of variant histology (VH) have been extensively studied in bladder cancer; however, further investigation is needed in upper tract urothelial carcinoma (UTUC). Our study aims to evaluate the impact of VH on oncological outcomes in UTUC patients treated with radical nephroureterectomy (RNU)., Methods: A retrospective analysis was performed on patients who underwent a robotic or laparoscopic RNU for UTUC using the ROBUUST database, a multi-institutional collaborative including 17 centers worldwide. Logistic regression was used to assess the effect of VH on urothelial recurrence (bladder, contralateral upper tract), metastasis, and survival following RNU., Results: A total of 687 patients were included in this study. Median (IQR) age was 71 (64-78) years and 470 (68%) had organ confined disease. VH was present in 70 (10.2%) patients. In a median follow-up of 16 months, the incidence of urothelial recurrence, metastasis, and mortality was 26.8%, 15.3%, and 11.8%, respectively. VH was associated with increased risk of metastasis (HR 4.3, P <.0001) and death (HR 2.0, P =.046). In multivariable analysis, VH was noted to be an independent risk factor for metastasis (HR 1.8, P =.03) but not for urothelial recurrence (HR 0.99, P =.97) or death (HR 1.4, P =.2)., Conclusion: Variant histology can be found in 10% of patients with UTUC and is an independent risk factor for metastasis following RNU. Overall survival rates and the risk of urothelial recurrence in the bladder or contralateral kidney are not affected by the presence of VH., Competing Interests: Disclosure The authors have stated that they have no conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objectives: To identify patient risk factors that predict nonhome discharge after surgery for urologic malignancies as well as determine whether discharge status had an impact on readmission rates in patients undergoing surgery for urologic malignancies., Methods: We identified patients who had undergone surgery for urologic malignancies including prostate, bladder, kidney, or upper tract urothelial cancer from 2011 to 2019 in the American College of Surgeon National Surgical Quality Improvement Program (ACS-NSQIP) database. Multivariable logistic regression analyses were performed to identify patient characteristics that were associated with nonhome discharges and 30-day postoperative readmission., Results: Nonhome discharge occurred in 2.8% of our study population. Women were less likely to be discharged to home (OR 0.60 p < 0.0001). Nonhome discharge was more common in patients who underwent cystectomy when compared to nephrectomy (OR 1.41 p < 0.0001) or prostatectomy (OR 4.16 p < 0.0001). Those with elevated BMI were less likely to experience non-home discharge (OR 0.86 p=0.0095) while patients who were identified as underweight and those with unexpected weight loss prior to surgery were more likely to have nonhome discharges (OR 1.76 p = 0.0002, OR 1.67, p < 0.0001). Comorbidities and presence of postoperative complications were also found to be significant independent predictors of nonhome discharges. Thirty-day postoperative readmission occurred in 6.9% of our study population. Of the patients who were readmitted 93.1% were initially discharged home, and 6.9% had nonhome discharges. Higher risk of readmission was seen in elderly patients and those with significant comorbidities. When controlling for predictors of readmission, on multivariate analysis, non-home discharge was associated with a decreased likelihood of readmission (OR 0.79, p = 0.0004)., Conclusions: Patient factors including age, gender, weight, comorbidities, postoperative complications, and site of procedure were found to be independent predictors of non-home discharge following surgery for urologic malignancies. Patients with these risk factors should be counseled preoperatively on the likelihood of requiring a non-home discharge to help manage expectations and create a standardized transition of care pathway following surgery., Competing Interests: Declaration of Competing Interest I, nor any of the authors of this paper have any competing interest or anything to disclose., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: Perioperative intravesical chemotherapy (IVC) at or around the time of radical nephroureterectomy (RNU) reduces the risk of intravesical recurrence. Guidelines since 2013 have recommended its use. The objective of this study is to examine IVC utilization and determine predictors of its administration within a large international consortium., Methods and Materials: Data was collected from 17 academic centers on patients who underwent robotic/laparoscopic RNU between 2006 and 2020. Patients who underwent concomitant radical cystectomy and cases in which IVC administration details were unknown were excluded. Univariate and multivariate analyses were utilized to determine predictors of IVC administration. A Joinpoint regression was performed to evaluate utilization by year., Results: Six hundred and fifty-nine patients were included. A total of 512 (78%) did not receive IVC while 147 (22%) did. Non-IVC patients were older (P < 0.001), had higher ECOG scores (P = 0.003), and had more multifocal disease (23% vs. 12%, P = 0.005). Those in the IVC group were more likely to have higher clinical T stage disease (P = 0.008), undergone laparoscopic RNU (83% vs. 68%, P < 0.001), undergone endoscopic management of the bladder cuff (20% vs. 4%, P = 0.008). Multivariable regression showed that decreased age (OR 0.940, P < 0.001), laparoscopic approach (OR 2.403, P = 0.008), and endoscopic management of the bladder cuff (OR 7.619, P < 0.001) were significant predictors favoring IVC administration. Treatment at a European center was associated with lower IVC use (OR 0.278, P = 0.018). Overall utilization of IVC after the 2013 European Association of Urology (EAU) guideline was 24% vs. 0% prior to 2013 (P < 0.001). Limitations include limited data regarding IVC timing/agent and inclusion of minimally invasive RNU patients only., Conclusions: While IVC use has increased since being added to the EAU UTUC guidelines, its use remains low at academic centers, particularly within Europe., Competing Interests: Conflict of interest The authors have no conflict of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: We investigated the relationship between timing of adjuvant chemotherapy on overall survival following radical cystectomy., Methods: We retrospectively reviewed the National Cancer Data Base for patients with newly diagnosed pT2-T4, N0, M0 urothelial cell carcinoma who received no treatment prior to radical cystectomy. Patients who received no adjuvant chemotherapy or who received adjuvant chemotherapy more than 45 days after radical cystectomy were propensity matched to patients receiving adjuvant chemotherapy within 45 days of radical cystectomy. Selection bias was assessed by comparing the length of stay, readmission rate, and surgical approach between groups. Median survival was calculated using Kaplan-Meier analysis. Adjusted hazard ratios and 95% confidence intervals were calculated from a multivariable Cox regression model to examine factors affecting overall survival., Results: From 2004 to 2014, 284 patients with muscle-invasive bladder cancer met inclusion criteria. Patients receiving chemotherapy within 45 days had the best 5-year overall survival (47.0%, 95%CI: 40.6%-53.2%) compared to those receiving chemotherapy after 45 days (37.5%, 95%CI: 31.4%-43.7%). Chemotherapy after 45 days and no adjuvant chemotherapy were significant predictors of worse overall survival compared to chemotherapy within 45 days (1.27, 1.02-1.59, P = 0.033 and 1.41, 1.12-1.78, P = 0.003). Receiving no adjuvant chemotherapy was not significantly different than chemotherapy after 45 days (1.11, 0.89-1.38, P = 0.348). Significant predictors of poorer overall survival were female sex (1.37, 1.04-1.81, P = 0.028), Medicare (1.37, 1.06-1.76, P = 0.016), pT3 stage (1.79, 1.35-2.38, P < 0.001), and pT4 stage (3.00, 2.20-4.01, P < 0.001). Significantly more patients with length of stay ≤7 days following RC received chemotherapy within 45 days (53.2%) compared to those who received adjuvant chemotherapy after 45 days after RC (44.0%) or no adjuvant chemotherapy (43.0%; P = 0.0369)., Conclusions: Initiation of adjuvant chemotherapy within 45 days of radical cystectomy for patients with pT2-4 bladder cancer was associated with an overall survival benefit compared to patients who received adjuvant chemotherapy after 45 days or no adjuvant chemotherapy., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Contemporary randomized controlled trials exploring adjuvant chemotherapy (AC) for bladder cancer (BCa) have yielded inconsistent results due to premature termination and/or poor patient accrual., Objective: To compare efficacy of AC vs. observation after radical cystectomy stratified by disease stage in a propensity-matched cohort., Design, Setting, and Participants: We performed a retrospective study that included patients who underwent radical cystectomy for any pT, N0-1, M0 BCa from the National Cancer Data Base (2004-2014). Patients who underwent AC were 1:1 propensity matched with patients who received observation only., Outcome Measurements and Statistical Analysis: Overall survival was assessed with multivariable Cox regression models where adjusted hazard ratios (aHR) and 95% confidence intervals (95% CI) were calculated., Results and Limitations: After coarsened exact 1:1 propensity matching, 3,066 patients (AC 1,533; observation 1,533) were included in the analysis. There were no significant differences in patient-, facility-, or tumor-level characteristics among cohorts. Compared with patients who underwent observation, recipients of AC had improved overall survival (aHR 0.67; 95% CI 0.61-0.74). Patients with pT2-4, pN1 disease significantly benefited from AC. Among the pN0 cohort, improved survival from AC was observed only in stages pT3 (aHR 0.67; 95% CI 0.55-0.83) and pT4 (aHR 0.70; 95% CI 0.50-0.98)., Conclusions: AC was associated with improved survival in locally advanced (pT3-4, pN0) and regionally advanced (pT2-4, pN1) chemotherapy-naive BCa., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Introduction: We assessed the impact of open or minimally-invasive partial cystectomy on surgical margin status in a nationwide hospital-based cohort., Materials and Methods: Patients who underwent partial cystectomy from 2010 to 2014 were identified in the National Cancer Data Base. The primary outcome was surgical margin status. A multivariable logistic regression model was fitted to identify patient, hospital, and surgical factors associated with positive surgical margins (PSMs)., Results: Partial cystectomy was performed in 1,118 patients via open (n = 715, 64%), laparoscopic (n = 209, 19%), and robotic (n = 194, 17%) approaches. Overall, 220 (19.7%) patients had PSMs. The PSM rate by surgical approach was 19.6% for open, 18.2% for laparoscopic, and 21.6% for robotic (P = 0.678). Compared to open partial cystectomy, the laparoscopic (aOR 1.06, 95%CI 0.70-1.60, P = 0.782), and robotic (aOR 1.28, 95%CI 0.85-1.91, P = 0.235) approaches were not significantly different in terms of PSM rate. There were higher odds of PSMs in non-Hispanic blacks (aOR 1.93, 95%CI 1.09-3.39, P = 0.023) compared to non-Hispanic whites, and in patients with muscle invasive bladder cancer (aOR 3.28, 95%CI 2.00-5.37, P < 0.001) or tumor size ≥ 3 cm (aOR 1.67, 95%CI 1.21-2.30, P = 0.002). Tumors in a dome/urachal location had lower odds of a PSM compared to tumors in a nondome/urachal location (aOR 0.67, 95%CI 0.47-0.94, P = 0.022)., Conclusions: Our results suggest that partial cystectomy using a laparoscopic or robotic-assisted approach is not associated with an increased risk of PSMs compared to open partial cystectomy., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: To determine whether a specific lymph node yield (LNY) affects overall survival (OS) in patients with penile cancer., Materials and Methods: Using the National Cancer Database, we identified 364 men diagnosed with pSCC who underwent ILND between 2004 and 2013. Men diagnosed on autopsy or at the time of death, patients with preoperative chemotherapy or radiotherapy, M+ and N3 disease, or with less than 3-month of follow-up were excluded. Kaplan-Meier analysis was used to compare Overall Survival (OS). A multivariable Cox regression model was developed to assess predictors of OS., Results: The median number of LN retrieved was 16 (IQR: 9-23). There was no significant difference in race, stage, grade for men with LNY ≤15 vs. >15. However, men with LNY ≤15 were significantly older than those with LNY >15 (65 vs. 59 years, p<0.001). On multivariable analysis, radical surgery, age, N+ disease, and LNY ≤15 were independent predictors of worse OS. Patients with LNY ≤15 showed significantly worse 5-year OS versus those with LNY >15 (49% vs. 67%, p=0.008). Nodal density (ND) ≥12.5% was also associated with decreased 5-year OS versus ND <12.5% (31% vs. 70%, p<0.0001)., Conclusions: LNY following ILND for pSCC appears to be an independent predictor of OS. A total LNY of >15 following ILND may have a beneficial impact on OS and serve as the threshold for defining an adequate ILND., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Radical cystectomy is the surgical standard for invasive bladder cancer. Robot-assisted cystectomy has been proposed to provide similar oncological outcomes with lower morbidity. We aimed to compare progression-free survival in patients with bladder cancer treated with open cystectomy and robot-assisted cystectomy., Methods: The RAZOR study is a randomised, open-label, non-inferiority, phase 3 trial done in 15 medical centres in the USA. Eligible participants (aged ≥18 years) had biopsy-proven clinical stage T1-T4, N0-N1, M0 bladder cancer or refractory carcinoma in situ. Individuals who had previously had open abdominal or pelvic surgery, or who had any pre-existing health conditions that would preclude safe initiation or maintenance of pneumoperitoneum were excluded. Patients were centrally assigned (1:1) via a web-based system, with block randomisation by institution, stratified by type of urinary diversion, clinical T stage, and Eastern Cooperative Oncology Group performance status, to receive robot-assisted radical cystectomy or open radical cystectomy with extracorporeal urinary diversion. Treatment allocation was only masked from pathologists. The primary endpoint was 2-year progression-free survival, with non-inferiority established if the lower bound of the one-sided 97·5% CI for the treatment difference (robotic cystectomy minus open cystectomy) was greater than -15 percentage points. The primary analysis was done in the per-protocol population. Safety was assessed in the same population. This trial is registered with ClinicalTrials.gov, number NCT01157676., Findings: Between July 1, 2011, and Nov 18, 2014, 350 participants were randomly assigned to treatment. The intended treatment was robotic cystectomy in 176 patients and open cystectomy in 174 patients. 17 (10%) of 176 patients in the robotic cystectomy group did not have surgery and nine (5%) patients had a different surgery to that they were assigned. 21 (12%) of 174 patients in the open cystectomy group did not have surgery and one (1%) patient had robotic cystectomy instead of open cystectomy. Thus, 302 patients (150 in the robotic cystectomy group and 152 in the open cystectomy group) were included in the per-protocol analysis set. 2-year progression-free survival was 72·3% (95% CI 64·3 to 78·8) in the robotic cystectomy group and 71·6% (95% CI 63·6 to 78·2) in the open cystectomy group (difference 0·7%, 95% CI -9·6% to 10·9%; p non-inferiority =0·001), indicating non-inferiority of robotic cystectomy. Adverse events occurred in 101 (67%) of 150 patients in the robotic cystectomy group and 105 (69%) of 152 patients in the open cystectomy group. The most common adverse events were urinary tract infection (53 [35%] in the robotic cystectomy group vs 39 [26%] in the open cystectomy group) and postoperative ileus (33 [22%] in the robotic cystectomy group vs 31 [20%] in the open cystectomy group)., Interpretation: In patients with bladder cancer, robotic cystectomy was non-inferior to open cystectomy for 2-year progression-free survival. Increased adoption of robotic surgery in clinical practice should lead to future randomised trials to assess the true value of this surgical approach in patients with other cancer types., Funding: National Institutes of Health National Cancer Institute., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Neoadjuvant radiotherapy (NART) for muscle-invasive bladder cancer (MIBC) is currently underused. However, the outcomes for MIBC have remained suboptimal. We investigated the relationship of NART to cause-specific mortality (CSM) and overall mortality (OM) among patients with a diagnosis of MIBC., Materials and Methods: The patients diagnosed with primary invasive urothelial carcinoma of the bladder from 1983 to 2008 with localized disease were included. Patients aged > 90 years, those diagnosed with T1 or T4 BC, and those with no information on tumor grade were excluded from the analysis. Kaplan-Meier, Cox regression, and competing risk methods were used in the analysis of OM and CSM., Results: A total of 5562 patients were included in the cohort (115 NART and 5447 surgery alone). On univariate analysis, NART significantly decreased the OM for patients with high-grade BC (hazard ratio [HR], 0.8), stage T2b (HR, 0.74), and stage T2b/T3 (HR, 0.74). CSM was also lower for those with stage T2b disease (HR, 0.63). Multivariable analysis revealed that NART was associated with a significant decrease in CSM (P = .043) and OM (P = .0462) for those with T2b. Likewise, an improvement was seen in OM (P = .0337) for patients with T2b/T3 who had received NART., Conclusion: NART was significantly associated with decreased CSM and OM in patients with clinical T2b/T3 BC and OM for patients with T2b/T3. These data suggest that NART could be beneficial in patients with T2b/T3 BC. In the modern era, the greatest utility would potentially be for patients with an incomplete response to neoadjuvant chemotherapy or as an adjunct to chemotherapy to improve the complete response rates., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objectives: Elevated polycomb group protein Enhancer of Zest Homolog 2 (EZH2) expression has been associated with progression to more advanced disease in a variety of malignancies. We examined EZH2 protein expression levels in bladder tissue specimens from patients with urothelial carcinoma (UC) and investigated the relationship between EZH2 protein expression and clinical outcomes., Materials and Methods: Tissue microarrays (TMAs) were constructed using bladder tissue specimens from radical cystectomies performed for UC at our institution between 1994 and 2002. EZH2 expression was measured by immunohistochemistry and scoring was based on percentage and intensity of positive nuclear staining. A receiver operating curve (ROC) was generated to differentiate cancerous from benign lesions using EZH2 protein scores. Recurrence-free survival was estimated using the Kaplan-Meier approach with log-rank test. A multivariate Cox proportional hazards model was used to assess independent contributions., Results: A total of 454 TMA specimen spots from 81 patients were evaluated. EZH2 protein levels in invasive high grade UC were significantly elevated compared with adjacent benign urothelium, noninvasive low grade UC, and CIS. EZH2 protein levels were also significantly increased in CIS and noninvasive low grade UC compared with adjacent benign urothelium. We found no association between EZH2 protein expression and clinical outcomes following radical cystectomy in our cohort of patients., Conclusion: EZH2 overexpression is a common event in UC of the bladder. Elevated EZH2 protein levels are associated with more aggressive bladder cancer, including invasive UC. EZH2 may therefore serve as a useful biomarker for UC., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Robotic-assisted surgery has become an increasingly popular approach to the treatment of a variety of urologic malignancies. The use of minimally invasive techniques for treatment of genitourinary cancers has evolved from conventional laparoscopy to the use of robotic-assisted instrumentation. Many questions remain regarding the safest and most effective way to teach robotic surgery to trainees. Work hour restrictions, medical and legal concerns, and the unique operative set-up of the robotic system have made it increasingly difficult to provide "hands on" operative training to residents and fellows. We review the current literature regarding robotic surgical training, highlight potentially effective training strategies, and discuss future improvements in robotic surgical training of the urologic oncologist.

Alterations in global levels and regional patterns of deoxyribonucleic acid methylation are among the earliest and most common events known to occur in human cancer. The mutational and epigenetic effects of this covalent deoxyribonucleic acid modification to the development of bladder cancer are well recognized. The contribution of aberrant methylation to mutational hot spots located within genes, transcriptional silencing, and chromosomal instability is reviewed in the context of its relevance to bladder carcinogenesis. Understanding how such processes evolve during the progression of bladder cancer is essential for using these molecular changes in the clinical setting. The recent development of sensitive and specific techniques for quantifying methylation changes in urine specimens and bodily fluids underscores the potential use of this molecular marker for early detection and surveillance of bladder cancer. Further refinement of these molecular biological techniques holds much promise for the use of methylation markers for bladder cancer diagnosis, risk stratification, and disease prognostication.

Tumorigenesis begins with the disregulated growth of an abnormal cell that has acquired the ability to divide more rapidly than its normal counterparts (Nowell, P.C. (1976) Science, 194, 23-28 [1]). Alterations in global levels and regional changes in the patterns of DNA methylation are among the earliest and most frequent events known to occur in human cancers (Feinberg and Vogelstein (1983) Nature, 301, 89-92 ([2]); Gama-Sosa, M.A. et al. (1983) Nucleic Acids Res., 11, 6883-6894 ([3]); Jones, P.A. (1986) Cancer Res., 46, 461-466 [4]). These changes in methylation may impair the proper expression and/or function of cell-cycle regulatory genes and thus confer a selective growth advantage to affected cells. Developments in the field of cancer research over the past few years have led to an increased understanding of the role DNA methylation may play in tumorigenesis. Many of these studies have investigated two major mechanisms by which DNA methylation may lead to aberrant cell cycle control: (1) through the generation of transition mutations via deamination-driven events resulting in the inactivation of tumor suppressor genes, or (2) by altering levels of gene expression through epigenetic effects at CpG islands. The mechanisms by which the normal function of growth regulatory genes may become affected by the mutagenic and epigenetic properties of DNA methylation will be discussed in the framework of recent discoveries in the field.

Cytosine to thymine transition mutations at the CpG dinucleotide are the most common point mutations in cancer and genetic disease. We calculated the in vivo rate of CpG mutation in the primate germline by deriving a primordial consensus sequence for an Alu repetitive element which inserted into intron 6 of the primate p53 gene 35 to 55 million years ago. Comparison of this primordial sequence to the Alu sequence in intron 6 of present-day primates was used to determine the nature and rate of mutations which occurred during evolution. We estimate the half-life of a CpG nucleotide to be 24 to 60 million years, and the rate constant for mutation at this dinucleotide to be 1.2 x 1O(-8) to 2.9 x 1O(-8) years(-1). These results were confirmed by the analysis of a second Alu sequence in intron 10 of the p53 gene. The in vivo mutation rate is at least 1250-fold slower than the in vitro chemical rate of 5-methylcytosine deamination in double-stranded DNA, showing that current estimates of CpG mutation repair have been significantly underestimated. Furthermore, the mutability of the CpG dinucleotide has led to the depletion of this dinucleotide from the vertebrate genome, and calculations in this study suggest that current levels of the CpG dinucleotide in the primate genome are very close to a steady state equilibrium in which the rate of CpG mutation is equal to the rate of CpG formation by random mutation.