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Objective: To assess the impact of neoadjuvant chemotherapy (NAC) on survival outcomes in a contemporary cohort of patients with in upper tract urothelial carcinoma (UTUC)., Methods: The National Cancer Database was queried from 2004 to 2015 to identify subjects who underwent nephroureterectomy for UTUC. Kaplan-Meier method with log-rank test was performed to compare all-cause mortality between patients who received preoperative chemotherapy to those who did not at each pathologic (p) TNM stage group: T1-4N0, N+, and M+ disease. Associations for all-cause mortality were identified using an adjusted Cox regression analysis., Results: A total of 10,315 chemoeligible subjects were included in the analysis. A total of 296 (2.9%) of patients received NAC prior to NU. Kaplan-Meier survival curves of the entire cohort demonstrated an overall survival advantage associated with administration of NAC (P = .017). Stratified by clinical staging, subjects with nonorgan-confined tumors had improved overall survival outcomes with NAC administration (P = .012). On multivariate analysis there was a statistically significant improvement in overall survival between in patients who received NAC. Of patients in the preoperative chemotherapy group who had clinically nonorgan-confined disease, 27.1% had organ-confined disease at time of surgery compared to 1.4% of those who underwent surgery as initial therapy., Conclusion: In a contemporary cohort of subjects who underwent nephroureterectomy for UTUC, administration of NAC in patients with high-grade nonorgan-confined disease led to higher rates of pathologic downstaging and was associated with improved overall survival., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: To evaluate programmed death ligand 1 (PD-L1) staining fidelity between the primary tumor and associated lymph node metastases in bladder cancer. To secondarily evaluate whether neoadjuvant chemotherapy (NAC) affects this relationship., Methods: Sixty-seven subjects with residual bladder cancer on cystectomy and associated positive lymph nodes were identified between 2008 and 2015. PD-L1 staining of tumor cells was evaluated using H score and 49 specimens were also evaluated using combined positive score (CPS). Univariable and multivariable logistic regression analysis were used to assess how various clinical variables affected odds of PD-L1 fidelity between primary and metastatic tumors., Results: Tumor PD-L1 staining was concordant in 79.1% of cases and CPS was concordant in 79.6% of cases. NAC did not significantly impact odds of PD-L1 or CPS fidelity (OR 1.974, 95% CI 0.673-5.784, OR 0.500, 95% CI 0.093-2.700). Among clinical variables analyzed on univariable analysis of tumor PD-L1 fidelity, H-score, and PD-L1 staining intensity were associated with significantly increased odds of PD-L1 fidelity and the association with staining intensity was confirmed on multivariable analysis., Conclusion: PD-L1 fidelity between primary bladder tumors and nodal metastases was observed in >75% of cases in this study. Additionally, NAC was not shown to diminish this propensity to maintain PD-L1 staining status. Further standardization of immunohistochemistry of tumor and infiltrating imsmune cells in metastatic bladder cancer is needed to improve application of therapeutics., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: To elucidate potential biomarkers or mechanistic principles involved with the gut microbiota and its impact on prostate cancer pathogenesis., Materials and Methods: We performed a prospective case-control pilot study evaluating the gut microbiome of 20 men with either benign prostatic conditions (n = 8) or intermediate or high risk clinically localized prostate cancer (Gleason ≥4 + 3 cN0M0) (n = 12) undergoing care at tertiary referral center from September 1, 2015 to March 1, 2016. Key exclusion criteria included recent antibiotic use, significant gastrointestinal disorders, hormonal or systemic therapy for prostate cancer. Computational genomics analysis was performed on collected stool samples using MetaPhlAn2 and HUMAnN2 platforms. Linear discriminant analysis effect size method was used to support high-dimensional class comparisons to find biologically relevant features. Kruskal-Wallis sum-rank test was used to detect features with significant differential abundance with respect to class, with biological consistency investigated using a set of pairwise tests among subclasses using the Wilcoxon rank-sum test, both to an α ≤0.05., Results: Higher relative abundance of Bacteriodes massiliensis was seen in prostate cancer cases compared to controls. Faecalibacterium prausnitzii and Eubacterium rectalie had higher relative abundance among controls. Biologically significant differences were also found in relative gene, pathway, and enzyme abundance., Conclusion: Biologically significant differences exist in the gut microbial composition of men with prostate cancer compared to benign controls. These differences may play a role in the pathobiology of prostate cancer, and warrant further exploration., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: To investigate the role of early feeding on recovery after radical cystectomy and urinary diversion. Enhanced recovery protocols have helped to standardize postoperative recovery. This is the first study to directly review the impact of early feeding on recovery in a randomized multi-institutional protocol., Methods: From 2011 to 2014, patients at 2 large hospitals were randomized after radical cystectomy to receive access to liquids and then a regular diet on postoperative days 1 and 2 or conventional care with introduction of a liquid diet after return of bowel activity, typically days 3-5. Early ambulation, use of metoclopramide, and no nasogastric tube were standard for all patients. The study was powered to detect a 50% decrease in 90-day complication rate with secondary end points of length of stay, time to bowel activity, and time to diet tolerance. The study was terminated early due to slow accrual (102 of 328)., Results: Overall complications for the early vs standard groups were similar (34 vs 31, P = .86). Immediate inpatient and postdischarge complication rates were also similar (P = .63 and P = .44). Length of stay was not different (8.74 days vs 9.69 days, P = .43). Rates of ileus (27% vs 41%, P = .21) and return of bowel function (4.67 days vs 4.09 days, P = .62) were the same in arms., Conclusion: Although this prospective randomized study did not meet the accrual target, early introduction of diet was well tolerated and did not show a negative or positive difference in any outcomes. Enhanced recovery protocols standardize postoperative care and early feeding is a well-tolerated addition., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Radical cystectomy is the gold-standard management for muscle-invasive bladder cancer, and there is debate concerning the comparative effectiveness of robotic-assisted (RARC) versus open radical cystectomy (ORC)., Objective: To compare utilization, perioperative, cost, and survival outcomes of RARC versus ORC., Design, Setting, and Participants: We identified bladder urothelial carcinoma treated with RARC (n=439) or ORC (n=7308) during 2002-2012 using the Surveillance, Epidemiology, and End Results Program-Medicare linked data., Intervention: Comparison of RARC versus ORC., Outcome Measurements and Statistical Analysis: We used propensity score matching to compare perioperative and survival outcomes, including lymph node yield, perioperative complications, and healthcare costs., Results and Limitations: Utilization of RARC increased from 0.7% of radical cystectomies in 2002 to 18.5% in 2012 (p<0.001). Women comprised 13.9% versus 18.1% (p=0.007) of RARC versus ORC, respectively. RARC was associated with greater lymph node yield with 41.5% versus 34.9% having ≥10 lymph nodes removed (relative risk 1.1, 95% confidence interval [CI] 1.01-1.22, p=0.03) and shorter mean length of hospitalization at 10.1 (± standard deviation 7.1) d versus 11.2 (± 8.6) d (p=0.004). While inpatient costs were similar, RARC was associated with increased home healthcare utilization (relative risk 1.14, 95% CI 1.04-1.26, p=0.009) and higher 30-d (p<0.01) and 90-d (p<0.01) costs. With a median follow-up of 44 mo (interquartile range 16-78), overall survival (hazard ratio 0.88, 95% CI 0.74-1.05) and cancer-specific survival (hazard ratio 0.91, 95% CI 0.66-1.26) were similar., Conclusions: RARC provides equivalent perioperative and intermediate term outcomes to ORC. Additional long-term and randomized studies are needed for continued comparative effectiveness assessment of RARC versus ORC., Patient Summary: Our population-based US study demonstrates that robotic-assisted radical cystectomy has similar perioperative and survival outcomes albeit at higher costs., (Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: Long-term oncologic data on patients undergoing robot-assisted radical cystectomy (RARC) are limited and based largely on single-institution series., Objective: Report survival outcomes of patients who underwent RARC ≥5 yr ago., Design, Setting, and Participants: Retrospective review of the prospectively populated International Robotic Cystectomy Consortium multi-institutional database identified 743 patients with RARC performed ≥5 yr ago. Clinical, pathologic, and survival data at the latest follow-up were collected. Patients with palliative RARC were excluded. Final analysis was performed on 702 patients from 11 institutions in 6 countries., Intervention: RARC., Outcome Measurements and Statistical Analysis: Outcomes of interest, recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS) were plotted using Kaplan-Meier survival curves. A Cox proportional hazards model was used to identify factors that predicted outcomes., Results and Limitations: Pathologic organ-confined (OC) disease was found in 62% of patients. Soft tissue surgical margins (SMs) were positive in 8%. Median lymph node (LN) yield was 16, and 21% of patients had positive LNs. Median follow-up was 67 mo (interquartile range: 18-84 mo). Five-year RFS, CSS, and OS were 67%, 75%, and 50%, respectively. Non-OC disease and SMs were associated with poorer RFS, CSS, and OS on multivariable analysis. Age predicted poorer CSS and OS. Adjuvant chemotherapy and positive SMs were predictors of RFS (hazard ratio: 3.20 and 2.16; p<0.001 and p<0.005, respectively). Stratified survival curves demonstrated poorer outcomes for positive SM, LN, and non-OC disease. Retrospective interrogation and lack of contemporaneous comparison groups that underwent open radical cystectomy were major limitations., Conclusions: The largest multi-institutional series to date reported long-term survival outcomes after RARC., Patient Summary: Patients who underwent robot-assisted radical cystectomy for bladder cancer have acceptable long-term survival., (Copyright © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: Concerns remain whether robot-assisted radical cystectomy (RARC) compromises survival because of inadequate oncologic resection or alteration of recurrence patterns., Objective: To describe recurrence patterns following open radical cystectomy (ORC) and RARC., Design, Setting, and Participants: Retrospective review of 383 consecutive patients who underwent ORC (n=120) or RARC (n=263) at an academic institution from July 2001 to February 2014., Intervention: ORC and RARC., Outcome Measurements and Statistical Analysis: Recurrence-free survival estimates were illustrated using the Kaplan-Meier method. Recurrence patterns (local vs distant and anatomic locations) within 2 yr of surgery were tabulated. Cox regression models were built to evaluate the effect of surgical technique on the risk of recurrence., Results and Limitations: The median follow-up time for patients without recurrence was 30 mo (interquartile range [IQR] 5-72) for ORC and 23 mo (IQR 9-48) for RARC (p=0.6). Within 2 yr of surgery, there was no large difference in the number of local recurrences between ORC and RARC patients (15/65 [23%] vs 24/136 [18%]), and the distribution of local recurrences was similar between the two groups. Similarly, the number of distant recurrences did not differ between the groups (26/73 [36%] vs 43/147 [29%]). However, there were distinct patterns of distant recurrence. Extrapelvic lymph node locations were more frequent for RARC than ORC (10/43 [23%] vs 4/26 [15%]). Furthermore, peritoneal carcinomatosis was found in 9/43 (21%) RARC patients compared to 2/26 (8%) ORC patients. In multivariable analyses, RARC was not a predictor of recurrence. Limitations of the study include selection bias and a limited sample size., Conclusions: Within limitations, we found that RARC is not an independent predictor of recurrence after surgery. Interestingly, extrapelvic lymph node locations and peritoneal carcinomatosis were more frequent in RARC than in ORC patients. Further validation is warranted to better understand the oncologic implications of RARC., Patient Summary: In this study, the locations of bladder cancer recurrences following conventional and robotic techniques for removal of the bladder are described. Although the numbers are small, the results show that the distribution of distant recurrences differs between the two techniques., (Copyright © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Objective: To compare survival outcomes and diversion-related complications of patients with and without a history of pelvic irradiation who underwent radical cystectomy., Patients and Methods: Three hundred sixty-four patients underwent radical cystectomy for bladder cancer (BCa) from July 2001 to September 2013. Thirty-seven patients (10%) had a history of pelvic irradiation, and 327 (90%) did not. The Kaplan-Meier method and Cox regression models were applied to evaluate survival outcomes. Diversion-related complications were tabulated., Results: The proportion of non-organ-confined disease was numerically higher in irradiated than in nonirradiated patients (18 of 37 [49%] vs 117 of 327 [36%] patients, P = .1). The difference in the proportion of T4 disease between the 2 groups was statistically significant (13 of 37 [35%] irradiated vs 37 of 327 [11%] nonirradiated patients, P = .005). Pelvic lymph node dissection could not be performed in 7 of 37 irradiated patients. A nonurothelial carcinoma histology was more frequent in irradiated than in nonirradiated patients (5 of 37 [14%] vs 19 of 327 [6%], P = .003). At 3 years, BCa recurrence-free survival estimates were 70 ± 9% and 77 ± 3% (log-rank P = .5), and BCa-specific survival estimates were 64 ± 9% and 69 ± 3% (log-rank P = .4), for irradiated and nonirradiated patients, respectively. In multivariate analysis, a history of pelvic irradiation was not predictive of BCa recurrence or BCa-specific death. Rates of diversion-related complications did not differ between the 2 groups., Conclusion: BCa patients with a history of pelvic irradiation present with more advanced disease. Surgery remains difficult in this group of patients as pelvic lymph node dissection is omitted in approximately 1 of 5 patients. Within limitations, prior pelvic irradiation is not predictive of survival outcomes., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Conditional survival (CS) provides better estimates of the survival probability at each follow-up time, and its usefulness has been proven in several solid malignancies., Objective: To assess the changes in 5-yr CS rates after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC) and to determine how well-established prognostic factors evolve over time., Design, Setting, and Participants: We analysed data from 3544 patients treated with RNU at 15 international academic centres between 1989 and 2012., Intervention: RNU., Outcomes Measurements and Statistical Analysis: Conditional intravesical recurrence-free (IVRFS), cancer-specific survival (CSS), and overall survival (OS) estimates were calculated using the Kaplan-Meier method. A multivariable Cox regression model was used to calculate proportional hazard ratios for the prediction of mortality., Results and Limitations: The 5-yr bladder cancer recurrence-free survival, CSS, and OS rates were 54.9%, 72.2%, and 62.6%, respectively. Given a 1-, 2-, 3-, and 4-yr survivorship, the 5-yr conditional OS rates improved to 65.2%, 69.3%, 71.5%, and 73.0%, respectively. The 5-yr CS improvement was primarily noted among surviving patients with advanced-stage disease. The impact of pathologic parameters on CS estimates decreased over time for both CSS and OS, whereas the impact of age and gender increased with survivorship. No survival benefit was noted regarding the adjuvant chemotherapy status. Findings were confirmed upon multivariable analyses. Tumour location, the presence of carcinoma in situ, and the type of bladder cuff excision were continuously predictive for IVRFS whatever the survivorship. A limitation is the retrospective design., Conclusions: CS analysis demonstrates that the patient risk profile evolves during the post-RNU follow-up. The probability of survival markedly increases over time in patients having high-stage disease. The impact of prognostic pathologic features decreases over time and can disappear for long-term CS., Patient Summary: In this study, we found that the risk of intravesical recurrence, cancer-specific survival, and overall mortality evolves over the follow-up after surgery. Taking into account the survivorship provides better estimates of the survival probability at each follow-up time., (Copyright © 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Objective: To investigate the impact of cystectomy for the treatment of refractory benign disease secondary to radiation therapy on the health-related quality of life (HRQOL)., Methods: A retrospective review was performed on patients undergoing cystectomy for the management of treatment-refractory disease secondary to radiation therapy. Overall, 29 patients underwent cystectomy for refractory fistulas (n = 12, 41.4%), radiation cystitis (n = 12, 41.4%), pelvic pain (n = 4, 13.8%), or incontinence (n = 1, 3.4%) from 2004 to 2013. Preoperative and postoperative HRQOL were measured using a modified version of the Short Form version 2 (SF-36v2)., Results: A total of 19 patients (65.5%) reported a 30-day postoperative complication, of which 80% were Clavien grade I or II. Nineteen (65.5%) of the patients completed the SF-36v2 survey. Low scores were noted in the preoperative setting in the physical and mental health domains of these patients, especially in the role limitations due to health and emotional problems. Clinically meaningful improvements were noted in all the physical and mental health domains after cystectomy. Significant improvements were found in certain domains, namely in the level of pain control, general health, role limitations due to emotional problems, and social functioning (all P <.01)., Conclusion: Treatment-refractory disease from radiation therapy significantly impairs patients' HRQOL. Although cystectomy with urinary diversion is associated with perioperative complication risks, cystectomies can be safely performed in this high-risk population and significantly improve patients' physical and mental HRQOL. Further studies are needed to characterize the role of cystectomy in treatment-refractory disease from radiation therapy., (Copyright © 2015. Published by Elsevier Inc.)

Background: The impact of gender on the staging and prognosis of urothelial carcinoma of the bladder (UCB) is insufficiently understood., Objective: To assess gender-specific differences in pathologic factors and survival of UCB patients treated with radical cystectomy (RC)., Design, Setting, and Participants: Data from 8102 patients treated with RC (6497 men [80%] and 1605 women [20%]) for UCB between 1971 and 2012 were analyzed., Outcome Measurements and Statistical Analysis: Multivariable competing-risk regression analyses were performed to evaluate the relationship of gender on disease recurrence (DR) and cancer-specific mortality (CSM). We also tested the interaction of gender and tumor stage, nodal status, and lymphovascular invasion (LVI)., Results and Limitations: Female patients were older at the time of RC (p=0.033) and had higher rates of pathologic stage T3/T4 disease (p<0.001). In univariable, but not in multivariable analysis, female gender was associated with a higher risk of DR (p=0.022 and p=0.11, respectively). Female gender was an independent predictor for CSM (p=0.004). We did not find a significant interaction between gender and stage, nodal metastasis, or LVI (all p values >0.05)., Conclusions: We found female gender to be associated with a higher risk of CSM following RC. However, these findings do not appear to be explained by gender differences in pathologic stage, nodal status, or LVI. This gender disparity may be due to differences in care and/or the biology of UCB., (Copyright © 2013 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: Nodal metastasis is the strongest risk factor of disease recurrence in patients with localized prostate cancer (PCa) treated with radical prostatectomy (RP)., Objective: To develop a model that allows quantification of the likelihood that a pathologically node-negative patient is indeed free of nodal metastasis., Design, Setting, and Participants: Data from patients treated with RP and pelvic lymph node dissection (PLND; n=7135) for PCa between 2000 and 2011 were analyzed. For external validation, we used data from patients (n=4209) who underwent an anatomically defined extended PLND., Intervention: RP and PLND., Outcome Measurements and Statistical Analysis: We developed a novel pathologic (postoperative) nodal staging score (pNSS) that represents the probability that a patient is correctly staged as node negative based on the number of examined nodes and the patient's characteristics., Results and Limitations: In the development and validation cohorts, the probability of missing a positive node decreases with an increasing number of nodes examined. Whereas in pT2 patients, a 90% pNSS was achieved with one single examined node in both the development and validation cohort, a similar level of nodal staging accuracy was achieved in pT3a patients by examining five and nine nodes, respectively. The pT3b/T4 patients achieved a pNSS of 80% and 70% when 17 and 20 nodes in the development and validation cohort were examined, respectively. This study is limited by its retrospective design and multicenter nature. The number of nodes removed was not directly correlated with the extent/template of PLND., Conclusions: Every patient needs PLND for accurate nodal staging. However, a one-size-fits-all approach is too inaccurate. We developed a tool that indicates a node-negative patient is indeed free of lymph node metastasis by evaluating the number of examined nodes, pT stage, RP Gleason score, surgical margins, and prostate-specific antigen. This tool may help in postoperative decision making., (Copyright © 2013 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: Intravesical recurrence after radical nephroureterectomy (RNU) is a frequent event requiring intense cystoscopic surveillance. Recently, a prospective randomized clinical trial has shown that a single intravesical postoperative dose of mitomycin C (MMC) reduces the absolute risk of intravesical recurrence after RNU., Objective: The aim of the current study was to identify predictors of intravesical recurrence and to develop a tool to allow a risk-stratified approach supporting patient counseling for cystoscopic surveillance and postoperative intravesical MMC administration., Design, Setting, and Participants: We performed a retrospective analysis of 1839 patients with upper tract urothelial carcinoma (UTUC). The data set was split into a development cohort of 1261 patients from North America and a validation cohort of 578 patients from Europe., Interventions: RNU with bladder cuff excision was performed. The surgical approach was open in 1424 patients (77.4%) and laparoscopic in 415 patients (22.6%)., Outcome Measurements and Statistical Analyses: Univariable and multivariable Cox regression models addressed time to intravesical recurrence after RNU. We developed a nomogram for prediction of the probability of intravesical recurrence at 3, 6, 9, 12, 18, 24, and 36 mo. Predictive accuracy was quantified using the concordance index. Decision curve analysis was performed to evaluate the clinical benefit associated with the use of our nomograms., Results and Limitations: With a median follow-up of 45 mo, intravesical recurrence occurred in 577 patients (31%). The probability of intravesical recurrence-free survival at 6, 12, 24, and 36 mo was 85% ± 1%, 78% ± 1%, 68% ± 1%, and 47% ± 2%, respectively. In multivariable Cox regression analysis, advanced age, male gender, ureteral tumor location, laparoscopic surgical technique, endoscopic distal ureteral management, previous bladder cancer, higher tumor stage, concomitant carcinoma in situ, and lymph node involvement were all significantly associated with intravesical recurrence (p values ≤ 0.04). The nomograms were highly accurate for predicting intravesical recurrence in the external validation cohort (concordance index of 67.8% and 69.0% for the reduced model and the full model, respectively), and calibration plots revealed only minor overestimation beyond 24 mo. If one decided to perform postoperative instillation based on the risk of intravesical recurrence of 15% at 24 mo, one would spare 23% of the patients while not preventing only 0.3% of intravesical recurrences. The lack of information on the stage and grade of the intravesical recurrences is the main limitation of the study., Conclusions: Intravesical recurrence after RNU is a common event in patients with UTUC. We developed nomograms that predict intravesical recurrence after RNU with reasonable accuracy. Such nomograms could improve the clinical decision-making process with regard to cystoscopic surveillance scheduling and postoperative intravesical instillations of MMC after RNU., (Copyright © 2013. Published by Elsevier B.V.)

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.)

Background: There is a lack of consensus regarding the optimal approach to the bladder cuff during radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC)., Objectives: To compare the oncologic outcomes following RNU using three different methods of bladder cuff management., Design, Setting, and Participants: Retrospective analysis of 2681 patients treated with RNU for UTUC at 24 international institutions from 1987 to 2007., Intervention: Three methods of bladder cuff excision were performed: transvesical, extravesical, and endoscopic., Outcome Measurements and Statistical Analysis: Univariable and multivariable models tested the effect of distal ureter management on intravesical recurrence, recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS)., Results and Limitations: Of the 2681 patients, 1811 (67.5%) underwent the transvesical approach; 785 (29.3%), the extravesical approach; and 85 (3.2%), the endoscopic approach. There was no difference in terms of RFS, CSS, and OS among the three distal ureteral management approaches. Patients who underwent the endoscopic approach were at significantly higher risk of intravesical recurrence compared with those who underwent the transvesical (p=0.02) or extravesical approaches (p=0.02); the latter two groups did not differ from each other (p=0.40). Actuarial intravesical RFS estimates at 2 and 5 yr after RNU were 69% and 58%, 69% and 51%, and 61% and 42% for the transvesical, extravesical, and endoscopic approaches, respectively. In multivariate analyses, distal ureteral management (p=0.01), surgical technique (open vs laparoscopic; p=0.02), previous bladder cancer (p<0.001), higher tumor stage (trend; p=0.01), concomitant carcinoma in situ (CIS) (p<0.001), and lymph node involvement (trend; p<0.001) were all associated with intravesical recurrence. Excluding patients with history of previous bladder cancer, all variables remained independent predictors of intravesical recurrence., Conclusions: The endoscopic approach was associated with higher intravesical recurrence rates. Interestingly, concomitant CIS in the upper tract is a strong predictor of intravesical recurrence after RNU. The association of laparoscopic RNU with intravesical recurrence needs to be further investigated., (Copyright © 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: Few studies have investigated the natural history of TaG1 urothelial carcinoma of the bladder (UCB)., Objective: To assess the long-term outcomes of patients with TaG1 UCB and the impact of immediate postoperative instillation of chemotherapy (IPIC)., Design, Setting, and Participants: A retrospective analysis of 1447 patients with TaG1 UCB treated between 1996 and 2007 at eight centers. Median follow-up was 67.2 mo (interquartile range: 67.9). Patients were stratified into three European Association of Urology (EAU) guidelines risk categories; high-risk patients (n=11) were excluded., Intervention: Transurethral resection of the bladder with or without IPIC., Outcome Measurements and Statistical Analysis: Univariable and multivariable Cox regression models addressed factors associated with disease recurrence, disease progression, death of disease, and any-cause death., Results and Limitations: Of the 1436 patients, 601 (41.9%) and 835 (58.1%) were assigned to low- and intermediate-risk categories, respectively. The actuarial estimate of 5-yr recurrence-free survival was 56% (standard error: ± 1). Advancing age (p=0.04), tumor >3 cm (p=0.001), multiple tumors (p<0.001), and recurrent tumors (p<0.001) were independently associated with increased risk of disease recurrence, whereas IPIC was associated with decreased risk (p=0.001). The actuarial estimate of 5-yr progression-free survival was 95% ± 1. Advancing age (p<0.001) and multiple tumors (p=0.01) were independent risk factors for disease progression. Five-year cancer-specific survival was 98% ± 1. Advancing age (p=0.001) and previous recurrence (p=0.04) were associated with increased risk, whereas female gender (p=0.02) was associated with decreased risk of cancer-specific mortality. Compared with low-risk patients, intermediate-risk patients were at significantly higher risk of disease recurrence, disease progression, and cancer-specific mortality (all p<0.01). Limitations include the retrospective design of the study and the lack of a central pathology review., Conclusions: TaG1 UCB patients experience heterogeneous risks of disease recurrence. We validated the EAU guidelines risk stratification in TaG1 UCB patients. IPIC was associated with a reduced risk of disease recurrence in patients with low- and intermediate-risk TaG1 UCB., (Copyright © 2013 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Objective: To report oncologic outcomes and complications after robotic-assisted radical cystectomy (RARC)., Materials and Methods: From March 2004 to August 2011, 175 consecutive patients underwent RARC with extracorporeal urinary diversion at our institution by a single surgeon. The study design was prospective. Perioperative parameters and postoperative complications were prospectively collected using the modified Clavien system. Recurrence-free survival and cancer-specific survival curves were generated using the Kaplan-Meier method., Results: A total of 145 men and 30 women with a median age of 73 years and a median body mass index of 27 kg/m(2) underwent RARC. Four patients (2.3%) required conversion to open surgery because of difficulty to progress. One hundred nine patients (62%) underwent a transcutaneous ileal conduit, 40 patients (23%) an orthotopic neobladder, and 26 (15%) a continent cutaneous conduit. The median operating time was 360 minutes (interquartile range [IQR]: 300-420). The median estimated blood loss was 400 mL (IQR: 250-612), with a transfusion rate of 17.0%. The median postoperative length of stay was 7.0 days (IQR: 5.2-10). Early (<30 days) and late surgery-related complications (30-90 days) occurred in 74 (42%) and 59 (34%) patients, respectively. The perioperative mortality rate was 2.8%. The positive soft tissue surgical margins rate was 5%. The median number of lymph nodes removed was 19 (IQR: 12-28). The median follow-up was 37 months (IQR: 21.5-53.5). Actuarial recurrence-free survival and cancer-specific survival at 2, 3, and 5 years after RARC were 67%, 63%, 63% and 73%, 68%, 66%, respectively., Conclusion: RARC achieved mid-term oncologic efficacy. Moreover, the complication rates were comparable with open radical cystectomy series., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: Lymph node metastasis (LNM) is the most powerful pathologic predictor of disease recurrence after radical cystectomy (RC). However, the outcomes of patients with LNM are highly variable., Objective: To assess the prognostic value of extranodal extension (ENE) and other lymph node (LN) parameters., Design, Setting, and Participants: A retrospective analysis of 748 patients with urothelial carcinoma of the bladder and LNM treated with RC and lymphadenectomy without neoadjuvant therapy at 10 European and North American centers (median follow-up: 27 mo)., Intervention: All subjects underwent RC and bilateral pelvic lymphadenectomy., Outcome Measurements and Statistical Analysis: Each LNM was microscopically evaluated for the presence of ENE. The number of LNs removed, number of positive LNs, and LN density were recorded and calculated. Univariable and multivariable analyses addressed time to disease recurrence and cancer-specific mortality after RC., Results and Limitations: A total of 375 patients (50.1%) had ENE. The median number of LNs removed, number of positive LNs, and LN density were 15, 2, and 15, respectively. The rate of ENE increased with advancing pT stage (p<0.001). In multivariable Cox regression analyses that adjusted for the effects of established clinicopathologic features and LN parameters, ENE was associated with disease recurrence (hazard ratio [HR]: 1.89; 95% confidence interval [CI], 1.55-2.31; p<0.001) and cancer-specific mortality (HR: 1.90; 95% CI, 1.52-2.37; p<0.001). The addition of ENE to a multivariable model that included pT stage, tumor grade, age, gender, lymphovascular invasion, surgical margin status, LN density, number of LNs removed, number of positive LNs, and adjuvant chemotherapy improved predictive accuracy for disease recurrence and cancer-specific mortality from 70.3% to 77.8% (p<0.001) and from 71.8% to 77.8% (p=0.007), respectively. The main limitation of the study is its retrospective nature., Conclusions: ENE is an independent predictor of both cancer recurrence and cancer-specific mortality in RC patients with LNM. Knowledge of ENE status could help with patient counseling, clinical decision making regarding inclusion in clinical trials of adjuvant therapy, and tailored follow-up scheduling after RC., (Copyright © 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: Cigarette smoking is the best-established risk factor for urothelial carcinoma development., Objective: To elucidate the association of pretreatment smoking status, cumulative exposure, and time since smoking cessation on outcomes of patients with urothelial carcinoma of the bladder (UCB) treated with radical cystectomy (RC)., Design, Setting, and Participants: We retrospectively collected clinicopathologic and smoking variables, including smoking status, number of cigarettes per day (CPD), duration in years, and time since smoking cessation, for 1506 patients treated with RC for UCB. Lifetime cumulative smoking exposure was categorized as light short-term (≤20 CPD for ≤20 yr), light long-term (≤20 CPD for >20 yr), heavy short-term (>20 CPD for ≤20 yr), and heavy long-term (>20 CPD for >20 yr)., Intervention: RC and bilateral lymph node (LN) dissection without neoadjuvant chemotherapy., Outcome Measurements and Statistical Analysis: Logistic regression and competing risk analyses assessed the association of smoking with disease recurrence, cancer-specific mortality, and overall mortality., Results and Limitations: There was no difference in clinicopathologic factors between patients who had never smoked (20%), former smokers (46%), and current smokers (34%). Smoking status was associated with the cumulative incidence of disease recurrence (p=0.004) and cancer-specific mortality (p=0.016) in univariable analyses and with disease recurrence in multivariable analysis (p=0.02); current smokers had the highest cumulative incidences. Among ever smokers, cumulative smoking exposure was associated with advanced tumor stages (p<0.001), LN metastasis (p=0.002), disease recurrence (p<0.001), cancer-specific mortality (p=0.001), and overall mortality (p=0.037) in multivariable analyses that adjusted for standard characteristics; heavy long-term smokers had the worst outcomes, followed by light long-term, heavy short-term, and light short-term smokers. Smoking cessation ≥10 yr mitigated the risk of disease recurrence (hazard ratio [HR]: 0.44; p<0.001), cancer-specific mortality (HR: 0.42; p<0.001), and overall mortality (HR: 0.69; p=0.012) in multivariable analyses. The study is limited by its retrospective nature., Conclusions: Smoking is associated with worse prognosis after RC for UCB. This association seems to be dose-dependent, and its effects are mitigated by >10 yr smoking cessation. Health care practitioners should counsel smokers regarding the detrimental effects of smoking and the benefits of smoking cessation on UCB etiology and prognosis., (Copyright © 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: Complication reporting is highly variable and nonstandardized. Therefore, it is imperative to determine the surgical outcomes of major oncologic procedures., Objective: To describe the complications after robot-assisted radical cystectomy (RARC) using a standardized and validated reporting methodology., Design, Setting, and Participants: Using the International Robotic Cystectomy Consortium (IRCC) database, we identified 939 patients who underwent RARC, had available complication data, and had at least 90 d of follow-up., Outcome Measurements and Statistical Analysis: Complications were analyzed and graded according to the Memorial Sloan-Kettering Cancer Center (MSKCC) system and were defined and stratified by organ system. Secondary outcomes included identification of preoperative and intraoperative variables predicting complications. Logistic regression models were used to define predictors of complications and readmission., Results and Limitations: Forty-one percent (n=387) and 48% (n=448) of patients experienced a complication within 30 and 90 d of surgery, respectively. The highest grade of complication was grade 0 in 52%, grade 1-2 in 29%, and grade 3-5 in 19% patients. Gastrointestinal, infectious, and genitourinary complications were most common (27%, 23%, and 17%, respectively). On multivariable analysis, increasing age group, neoadjuvant chemotherapy, and receipt of blood transfusion were independent predictors of any and high-grade complications, respectively. Thirty and 90-d mortality was 1.3% and 4.2%, respectively. As a multi-institutional database, a disparity in patient selection, operating standards, postoperative management, and reporting of complications can be considered a major limitation of the study., Conclusions: Surgical morbidity after RARC is significant when reported using a standardized reporting methodology. The majority of complications are low grade. Strict reporting of complications is necessary to advocate for radical cystectomy (RC) and helps in patient counseling., (Copyright © 2013 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: Cigarette smoking is a common risk factor for developing upper tract urothelial carcinoma (UTUC)., Objective: To assess the impact of cigarette smoking status, cumulative smoking exposure, and time from cessation on oncologic UTUC outcomes in patients treated with radical nephroureterectomy (RNU)., Design, Setting, and Participants: A total of 864 patients underwent RNU at five institutions. The median follow-up in this retrospective study was 50 mo. Smoking history included smoking status, quantity of cigarettes per day (CPD), duration in years, and years from smoking cessation. The cumulative smoking exposure was categorized as light-short-term (≤ 19 CPD and ≤ 19.9 yr), moderate (all combinations except light-short-term and heavy-long-term), and heavy-long-term (≥ 20 CPD and ≥ 20 yr)., Interventions: RNU with or without lymph node dissection. No patient received neoadjuvant chemotherapy., Outcome Measurements and Statistical Analysis: Univariable and multivariable logistic regression and competing risk regression analyses assessed the effects of smoking on oncologic outcomes., Results and Limitations: A total of 244 patients (28.2%) never smoked; 297 (34.4%) and 323 (37.4%) were former and current smokers, respectively. Among smokers, 87 (10.1%), 331 (38.3%), and 202 (23.4%) were light-short-term, moderate, and heavy-long-term smokers, respectively. Current smoking status, smoking ≥ 20 CPD, ≥ 20 yr, and heavy-long-term smoking were associated with advanced disease (p values ≤ 0.004), greater likelihood of disease recurrence (p values ≤ 0.01), and cancer-specific mortality (p values ≤ 0.05) on multivariable analyses that adjusted for standard features. Patients who quit smoking ≥ 10 yr prior to RNU did not differ from never smokers regarding advanced tumor stages, disease recurrence, and cancer-specific mortality, but they had better oncologic outcomes then current smokers and those patients who quit smoking <10 yr prior to RNU. The study is limited by its retrospective nature., Conclusions: Cigarette smoking is significantly associated with advanced disease stages, disease recurrence, and cancer-specific mortality in patients treated with RNU for UTUC. Current smokers and those with a heavy and long-term smoking exposure have the highest risk for poor oncologic outcomes. Smoking cessation >10 yr prior to RNU seems to mitigate some detrimental effects. These results underscore the need for smoking cessation and prevention programs., (Copyright © 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: Cigarette smoking is the best-established risk factor for urothelial carcinoma (UC) development, but the impact on oncologic outcomes remains poorly understood., Objective: To analyse the effects of smoking status, cumulative exposure, and time from smoking cessation on the prognosis of patients with primary non-muscle-invasive bladder cancer (NMIBC)., Design, Setting, and Participants: We collected smoking data from 2043 patients with primary NMIBC. Smoking variables included smoking status, average number of cigarettes smoked per day (CPD), duration in years, and time since smoking cessation. Lifetime cumulative smoking exposure was categorised as light short term (≤ 19 CPD, ≤ 19.9 yr), light long term (≤ 19 CPD, ≥ 20 yr), heavy short term (≥ 20 CPD, ≤ 19.9 yr) and heavy long term (≥ 20 CPD, ≥ 20 yr). The median follow-up in this retrospective study was 49 mo., Interventions: Transurethral resection of the bladder with or without intravesical instillation therapy., Outcome Measurements and Statistical Analysis: Univariable and multivariable logistic regression and competing risk regression analyses assessed the effects of smoking on outcomes., Results and Limitations: There was no difference in clinicopathologic factors among never (24%), former (47%), and current smokers (29%). Smoking status was associated with the cumulative incidence of disease progression in multivariable analysis (p=0.003); current smokers had the highest cumulative incidences. Among current and former smokers, cumulative smoking exposure was associated with disease recurrence (p<0.001), progression (p<0.001), and overall survival (p<0.001) in multivariable analyses that adjusted for the effects of standard clinicopathologic factors and smoking status; heavy long-term smokers had the worst outcomes, followed by light long-term, heavy short-term, and light short-term smokers. Smoking cessation >10 yr reduced the risk of disease recurrence (hazard ratio [HR]: 0.66; 95% confidence interval [CI], 0.52-0.84; p<0.001) and progression (HR: 0.42; 95% CI, 0.22-0.83; p=0.036) in multivariable analyses. The study is limited by its retrospective nature., Conclusions: Smoking status and a higher cumulative smoking exposure are associated with worse prognosis in patients with NMIBC. Smoking cessation >10 yr abrogates this detrimental effect. These findings underscore the need for integrated smoking cessation and prevention programmes in the management of NMIBC patients., (Copyright © 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: Radical cystectomy (RC) with pelvic lymph node dissection (PLND) is the standard of care for high-risk non-muscle-invasive and muscle-invasive bladder cancer (BCa)., Objective: To develop a model that allows quantification of the likelihood that a pathologically node-negative patient has, indeed, no positive nodes., Design, Setting, and Participants: We analyzed data from 4335 patients treated with RC and PLND without neoadjuvant chemotherapy at 12 international academic centers., Interventions: Patients underwent RC and PLND., Outcome Measurements and Statistical Analysis: We estimated the sensitivity of pathologic nodal staging using a beta-binomial model and developed a pathologic (postoperative) nodal staging score (pNSS) that represents the probability that a patient is correctly staged as node negative as a function of the number of examined nodes., Results and Limitations: Overall, the probability of missing a positive node decreases with the increasing number of nodes examined (52% if 3 nodes are examined, 40% if 5 are examined, and 26% if 10 are examined). The proportion of having a positive node increased proportionally with advancing pathologic T stage and lymphovascular invasion (LVI). Patients with LVI who had 25 examined nodes would have a pNSS of 80% (pT1), 88% (pT2), and 66% (pT3-T4), whereas 10 examined nodes were sufficient for pNSS exceeding 90% in patients without LVI and pT0-T2 tumors. This study is limited because of its retrospective design and multicenter nature., Conclusions: We developed a tool that estimates the likelihood of lymph node (LN) metastasis in BCa patients treated with RC by evaluating the number of examined nodes, the pathologic T stage, and LVI. The pNSS indicates the adequacy of nodal staging in LN-negative patients. This tool could help to refine clinical decision making regarding adjuvant chemotherapy, follow-up scheduling, and inclusion in clinical trials., (Copyright © 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: Dissimilarities in management and outcomes exist between upper tract urothelial carcinoma (UTUC) and urothelial carcinoma of the bladder (UCB)., Objective: The aim of this study was to analyze the stage-specific impact of upper or lower urinary tract tumor location on oncologic outcomes., Design, Setting, and Participants: Data were collected from 4335 patients with UCB treated with radical cystectomy (RC) and bilateral pelvic lymphadenectomy (PLND), 877 patients with ureteral UTUC, and 1615 with pelvicalyceal UTUC treated with radical nephroureterectomy (RNU). No patient received preoperative chemotherapy or radiation therapy., Interventions: Patients were treated with RC and bilateral PLND or RNU., Measurements: Outcomes were assessed according to primary tumor location., Results and Limitations: Compared to UTUC patients, UCB patients had more advanced tumor stage and higher grade, and they were more likely to harbor lymphovascular invasion (LVI) and lymph node metastasis (p<0.001). In non-muscle-invasive tumor stages, UCB patients were more likely to experience disease recurrence and mortality compared to renal pelvicalyceal tumor patients (p<0.002) but not ureteral tumors (p>0.05). In pT2 and pT3 tumors, there was no difference in outcomes between the three tumor locations. In pT4 tumors, patients with ureteral and pelvicalyceal tumors were more likely to experience disease recurrence and mortality compared to UCB patients (p<0.004). These stage-specific findings were unchanged after adjustment for the effects of age, gender, tumor grade, LVI, lymph node status, and adjuvant chemotherapy. This study is limited by its retrospective and multicenter nature., Conclusions: Stage-specific differences in outcomes exist between UCB and UTUC. The differentially worse outcomes by stage between UCB and UTUC patients underline the differences between both cancer entities and the need for individualized stage-specific management for each patient., (Copyright © 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: The clinical course of pT3 upper tract urothelial carcinoma (UTUC) is highly variable., Objectives: The aim of the current study was to validate the clinical and prognostic importance of pT3 subclassification in the renal pelvicalyceal system in a large international cohort of patients., Design, Setting, and Participants: From a multi-institutional international database, 858 renal pelvicalyceal tumors treated with radical nephroureterectomy (RNU) were systematically reevaluated by genitourinary pathologists. Category pT3 pelvic tumors were categorized as pT3a (infiltration of the renal parenchyma on a microscopic level only) versus pT3b (macroscopic infiltration of the renal parenchyma and/or infiltration of peripelvic adipose tissue)., Intervention: RNU., Measurements: Associations of pT3 subclassifications with clinicopathologic features were assessed with the chi-square test. Prognostic impact was assessed with the log-rank test and multivariable Cox regression analyses., Results and Limitations: Of 858 patients with renal pelvicalyceal tumors, 266 (31%) had pT3 disease. Of these, 146 (54.9%) were classified as pT3a and 120 (45.1%) as pT3b. Compared with pT3a, pT3b cancers were associated with higher tumor grade, nodal disease, and tumor necrosis. Ten-year recurrence-free (pT3a 58% vs pT3b 38%; p<0.001) and cancer-specific (pT3a 60% vs pT3b 39%; p=0.002) survival rates were lower for patients with pT3b disease. In multivariable analyses, classification pT3b was an independent predictor of both disease recurrence (hazard ratio [HR]: 1.8, p=0.003) and cancer-specific mortality (HR: 1.7; p=0.02). The major limitation is the retrospective character of the study., Conclusions: Subclassification of pT3 renal pelvicalyceal UTUC helps identify patients who are at increased risk of disease progression and cancer-related death. Further research may help assess the value of subclassification and its inclusion in future editions of the American Joint Committee on Cancer-International Union Against Cancer TNM classification system., (Copyright © 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: Novel prognostic factors for patients after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC) have recently been described., Objective: We tested the prognostic value of pathologic characteristics and developed models to predict the individual probabilities of recurrence-free survival (RFS) and cancer-specific survival (CSS) after RNU., Design, Setting, and Participants: Our study included 2244 patients treated with RNU without neoadjuvant or adjuvant therapy at 23 international institutions. Tumor characteristics included T classification, grade, lymph node status, lymphovascular invasion, tumor architecture, location, and concomitant carcinoma in situ (CIS). The cohort was randomly split for development (12 centers, n=1273) and external validation (11 centers, n=971)., Interventions: All patients underwent RNU., Measurements: Univariable and multivariable models addressed RFS, CSS, and comparison of discrimination and calibration with American Joint Committee on Cancer (AJCC) stage grouping., Results and Limitations: At a median follow-up of 45 mo, 501 patients (22.3%) experienced disease recurrence and 418 patients (18.6%) died of UTUC. On multivariable analysis, T classification (p for trend <0.001), lymph node metastasis (hazard ratio [HR]: 1.98; p=0.002), lymphovascular invasion (HR: 1.66; p<0.001), sessile tumor architecture (HR: 1.76; p<0.001), and concomitant CIS (HR: 1.33; p=0.035) were associated with disease recurrence. Similarly, T classification (p for trend<0.001), lymph node metastasis (HR: 2.23; p=0.001), lymphovascular invasion (HR: 1.81; p<0.001), and sessile tumor architecture (HR: 1.72; p=0.001) were independently associated with cancer-specific mortality. Our models achieved 76.8% and 81.5% accuracy for predicting RFS and CSS, respectively. In contrast to these well-calibrated models, stratification based upon AJCC stage grouping resulted in a large degree of heterogeneity and did not improve discrimination., Conclusions: Using standard pathologic features, we developed highly accurate prognostic models for the prediction of RFS and CSS after RNU for UTUC. These models offer improvements in calibration over AJCC stage grouping and can be used for individualized patient counseling, follow-up scheduling, risk stratification for adjuvant therapies, and inclusion criteria for clinical trials., (Copyright © 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: Radical cystectomy (RC) with pelvic lymph node dissection (LND) is the standard of care for refractory non-muscle-invasive and muscle-invasive bladder cancer. Although consensus exists on the need for LND, its extent is still debated., Objective: To develop a model that allows preoperative determination of the minimum number of lymph nodes (LNs) needed to be removed at RC to ensure true nodal status., Design, Setting, and Participants: We analyzed data from 4335 patients treated with RC and pelvic LND without neoadjuvant chemotherapy at 12 academic centers located in the United States, Canada, and Europe., Measurements: We estimated the sensitivity of pathologic nodal staging using a beta-binomial model and developed clinical (preoperative) nodal staging scores (cNSS), which represent the probability that a patient has LN metastasis as a function of the number of examined nodes., Results and Limitations: The probability of missing a positive LN decreased with an increasing number of nodes examined (52% if 3 nodes were examined, 40% if 5 were examined, and 26% if 10 were examined). A cNSS of 90% was achieved by examining 6 nodes for clinical Ta-Tis tumors, 9 nodes for cT1 tumors, and 25 nodes for cT2 tumors. In contrast, examination of 25 nodes provided only 77% cNSS for cT3-T4 tumors. The study is limited due to its retrospective design, its multicenter nature, and a lack of preoperative staging parameters., Conclusions: Every patient treated with RC for bladder cancer needs an LND to ensure accurate nodal staging. The minimum number of examined LNs for adequate staging depends preoperatively on the clinical T stage. Predictive tools can give a preoperative estimation of the likelihood of nodal metastasis and thereby allow tailored decision-making regarding the extent of LND at RC., (Copyright © 2011 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: The prognostic impact of multifocal upper-tract urothelial carcinoma (UTUC) is poorly understood., Objective: To investigate the association between tumor multifocality and clinicopathologic features and outcomes of UTUC in patients managed by radical nephroureterectomy (RNU)., Design, Setting, and Participants: The study included 2492 patients treated with either open or laparoscopic RNU. Tumor and patient characteristics included tumor stage, tumor grade, lymph node status, lymphovascular invasion (LVI), tumor architecture, tumor location, unifocal or multifocal disease, gender, age, history of bladder cancer (BCa), Eastern Cooperative Oncology Group (ECOG) performance status (PS), and adjuvant chemotherapy. tumor multifocality of UTUC was defined as the synchronous presence of multiple tumors in the renal pelvis or ureter., Intervention: All patients were treated with either open or laparoscopic RNU., Measurements: Univariable and multivariable models tested the effect of tumor multifocality on disease progression and cancer-specific mortality., Results and Limitations: Five hundred ninety patients (23.7%) had tumor multifocality at the time of RNU. The median follow-up was 45 mo (interquartile range [IQR]: 0-101). Tumor multifocality was significantly associated with a history of previous BCa (p=0.032), lymph node involvement (p=0.036), tumor location in the ureter (p=0.003), higher tumor stage (p<0.001), higher tumor grade (p<0.001), sessile tumor architecture (p=0.003), and LVI (p=0.001). In organ-confined patients, tumor multifocality was an independent predictor of both disease progression (hazard ratio [HR]: 1.43; p=0.019) and cancer-specific mortality (HR: 1.46; p=0.027). When assessed in all patients, tumor multifocality was associated with both disease progression and cancer-specific mortality in univariable (p=0.005 and p=0.006, respectively) but not in multivariable analyses (p=0.468 and p=0.798, respectively). The main limitation is the retrospective design of the study., Conclusions: Tumor multifocality is an independent prognosticator of disease progression and cancer-specific mortality in patients with organ-confined UTUC treated with RNU. Multifocal organ-confined patients with UTUC may need closer follow-up. Integration of tumor multifocality with other factors may help identify those patients who would benefit from multimodal therapy., (Copyright © 2011 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Objectives: Although the ileal conduit is the most well-established urinary diversion, the optimal technique for ureteroileal anastomosis remains controversial. Here, we present a technique for anastomosis of the ureters from within the lumen of the ileal conduit, under direct visualization. We examine the rate of ureteral stricture using this method, and review the literature regarding ureteroenteric anastomotic complications with various techniques., Methods: An intraluminal technique for ureteroenteric anastomsosis was performed by opening the conduit on the antimesenteric border to allow direct visualization of the ureteroileal anastomosis. Using our prospectively collected database, we investigated the prevalence of anastomotic stricture in patients undergoing urinary diversion using this method for anastomosis., Results: One-hundred eighteen patients underwent ileal conduit diversion with ureteroileal anastomoses performed as described. Median postoperative follow-up was 15 months. Ureteral strictures were identified in 5/118 patients (4.2%). Of the patients with strictures, one was successfully treated with endoscopic balloon dilatation, three were managed with chronic ureteral stents, and one was managed with a chronic percutaneous nephrostomy. Review of the recent literature reveals stricture rates up to 10% with current techniques., Conclusions: We conclude from these results that during ileal conduit creation, intraluminal anastomosis of the ureters to the ileal segment under direct vision represents a viable alternative to other techniques, with complication rates that compare favorably with other reported series., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Background: There is a lack of consensus regarding the prognostic significance of ureteral versus renal pelvic upper tract urothelial carcinoma (UTUC)., Objective: To investigate the association of tumor location on outcomes for UTUC in an international cohort of patients managed by radical nephroureterectomy (RNU)., Design, Setting, and Participants: A retrospective review of institutional databases from 10 institutions worldwide identified patients with UTUC., Intervention: The 1249 patients in the study underwent RNU with ipsilateral bladder cuff resection between 1987 and 2007., Measurements: Data accrued included age, gender, race, surgical approach (open vs laparoscopic), tumor pathology (stage, grade, lymph node status), tumor location, use of perioperative chemotherapy, prior endoscopic therapy, urothelial carcinoma recurrence, and mortality from urothelial carcinoma. Tumor location was divided into two groups (renal pelvis and ureter) based on the location of the dominant tumor., Results and Limitations: The 5-yr recurrence-free and cancer-specific survival estimates for this cohort were 75% and 78%, respectively. On multivariate analysis, only pathologic tumor (pT) classification (p<0.001), grade (p<0.02), and lymph node status (p<0.001) were associated with disease recurrence and cancer-specific survival. When adjusting for these variables, there was no difference in the probability of disease recurrence (hazard ratio [HR]: 1.22; p=0.133) or cancer death (HR: 1.23; p=0.25) between ureteral and renal pelvic tumors. Adding tumor location to a base prognostic model for disease recurrence and cancer death that included pT stage, tumor grade, and lymph node status only improved the predictive accuracy of this model by 0.1%. This study is limited by biases associated with its retrospective design., Conclusions: There is no difference in outcomes between patients with renal pelvic tumors and with ureteral tumors following nephroureterectomy. These data support the current TNM staging system, whereby renal pelvic and ureteral carcinomas are classified as one integral group of tumors., (Copyright © 2009 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: Robotic cystectomy is an emerging alternative for treatment of invasive bladder cancer (BCa). However, reduction in postoperative morbidity relative to the open approach has not been demonstrated., Objective: To compare complication rates in patients undergoing robotic versus open radical cystectomy (RC)., Design, Setting, and Participants: A prospective cohort study of 187 consecutive patients undergoing RC at our institution-104 open RC, 83 robotic RC., Intervention: Open or robotic RC with urinary diversion., Measurements: Demographic, perioperative, and complication data were recorded prospectively. Thirty-day and 90-d complication rates were assessed using the modified Clavien complication scale. Data were evaluated using chi(2) and multivariate logistic regression analyses., Results and Limitations: At 30 d, the open group demonstrated a higher overall complication rate (59% vs 41%; p=0.04) as well as more major complications (30% vs 10%; p=0.007). At 90 d, the overall complication rate was greater in the open group, but this was not statistically significant (62% vs 48%; p=0.07). However, there was a significantly higher major complication rate in the open cohort (31% vs 17%; p=0.03). When subjected to logistic regression analysis, robotic cystectomy was an independent predictor of fewer overall and major complications at 30 and 90 d. High American Society of Anesthesiologists (ASA) score (3-4) and longer surgical time were independent predictors of major complications. Though this is one of the largest published RC series, the sample size is relatively small. Moreover, despite the two patient cohorts being similarly matched, the study was not performed in a randomized fashion., Conclusions: Patients undergoing robotic cystectomy experienced fewer postoperative complications than those undergoing open cystectomy. Robotic cystectomy is an independent predictor of fewer overall and major complications. Until long-term oncologic results are available, robotic cystectomy should still be considered investigational., (Copyright 2009 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Objectives: To evaluate the effects of imidazoquinolines in renal cell carcinoma (RCC)., Methods: In vitro experiments were carried out using mouse (RENCA) and human (CAKI-1, CAKI-2, and A-498) RCC cell lines. Toll-like receptor-7 (TLR7) expression was assessed by Western blot. We determined the ability of imidazoquinolines to induce apoptosis and inhibit cell viability in vitro. For in vivo experiments, RENCA cells were injected into the tail vein of syngeneic mice. One week after injection, mice were given oral imidazoquinoline or placebo for 14 days. Mice were then sacrificed, and lungs were inspected for tumor nodules. Immunohistochemical staining was used to assess apoptosis in vivo., Results: Toll-like receptor-7 was expressed in all cell lines tested, with RENCA cells showing the highest level of expression. Imidazoquinolines inhibited in vitro cell viability of RENCA, CAKI-2, and A-498 cell lines in a time-dependent manner. Viability of CAKI-1 was not inhibited significantly. Apoptosis induction was pronounced in RENCA cells treated with imidazoquinoline. Compared with placebo, oral imidazoquinoline significantly reduced the number of pulmonary metastasis and increased cell death in vivo., Conclusions: Imidazoquinolines inhibit cell viability and cause deoxyribonucleic acid fragmentation leading to apoptosis in RCC cell lines, potentially working through the TLR7 expressed by RCC cell lines. Preliminary data from a mouse model of metastatic RCC also suggest antitumor effects and induction of apoptosis in vivo.

Objectives: To determine the pathologic features of bladder tumors after nephroureterectomy or segmental ureterectomy for upper urinary tract transitional cell carcinoma (UUT-TCC)., Methods: From 1993 to 2003, 82 patients without a history of bladder cancer underwent nephroureterectomy or segmental distal ureterectomy for UUT-TCC. We reviewed the pathologic features of the subsequent bladder tumors, including stage, grade, and progression to cystectomy in these patients at a median follow-up of 44.1 months., Results: A total of 36 (44%) of 82 patients developed bladder tumors after definitive therapy for UUT-TCC at a mean interval of 13.9 months. The mean number of bladder tumors diagnosed per patient in the follow-up interval was 2.1 (range 1 to 6), for a total of 74 bladder tumors. Of the 74 bladder tumors, 71 (96%) were superficial (Stage Ta, Tis, T1), 49 of these superficial tumors (69%) being low grade (grade 1 and 2) and 22 (31%) high grade (grade 3). Three patients had high-grade, muscle-invasive disease, and all progressed to cystectomy during follow-up. A greater than 75% concordance was found in pathologic grade between the UUT lesion and subsequent bladder tumors. The stage of the UUT malignancy, however, did not correlate with subsequent bladder tumor pathologic findings., Conclusions: Bladder tumors developed in 44% of patients after treatment of UUT-TCC. Of these bladder tumors, over 60% were superficial, low-grade lesions, yielding a similar pathologic distribution to that of bladder cancer de novo. The grade, but not the stage, of the UUT tumors correlated with the pathologic findings of subsequent bladder tumor recurrence. Aggressive surveillance with cystoscopy and urinary cytology after surgical management of UUT-TCC is imperative.

Objectives: To evaluate 5-alpha-reductase (5alphaR) expression in benign and malignant urothelium and to assess the relationship between 5alphaR expression and tumor stage, tumor grade, and clinical outcome in patients with urothelial carcinoma/transitional cell carcinoma., Methods: We performed immunohistochemistry for 5alphaR on 53 urothelial specimens from 36 patients with transitional cell carcinoma treated at our institution between June 2002 and July 2003. For each tumor and the adjacent nontumor urothelium, a semiquantitative staining score was calculated. We used t tests and analysis of variance to compare the staining score across groups. Kaplan-Meier and logistic regression analyses were performed to assess the relationship between 5alphaR expression and clinical outcome., Results: 5alphaR was expressed throughout the non-neoplastic urothelium. Nontumor urothelium had greater mean staining scores than did tumor specimens (160.1 versus 105.5, P <0.01). Low staining scores were associated with high grade (P <0.05), Stage pT3, pT4, and pTis (P <0.05), and disease progression (P <0.05). A staining score less than the median was a risk factor for progression (odds ratio 6.2, P <0.01) on univariate regression analysis. Patients with a staining score less than the median had a greater likelihood of disease progression (log-rank P <0.05) and cause-specific mortality (log-rank P <0.05)., Conclusions: We demonstrated 5alphaR expression in human urothelium and found that expression is decreased in transitional cell carcinoma in relation to tumor grade and stage. Decreased 5alphaR expression was associated with disease progression and cause-specific mortality.

Objectives: To investigate whether a delay in nephroureterectomy for patients with transitional cell carcinoma of the upper urinary tract owing to ureteroscopic biopsy and/or laser tumor ablation affects postoperative disease status., Methods: Of 155 patients diagnosed with upper tract transitional cell carcinoma at our institution from 1993 to 2003, 121 underwent nephroureterectomy. We compared the postoperative disease status of patients who underwent nephroureterectomy on the basis of positive cytology findings and filling defect on contrast imaging (no ureteroscopy; n = 34) to patients who underwent nephroureterectomy after ureteroscopic biopsy (n = 75) and patients who underwent nephroureterectomy after ureteroscopic biopsy and laser tumor ablation (n = 12)., Results: At a mean follow-up of 38.7 months, 29 (85.3%) of 34 patients who underwent nephroureterectomy on the basis of contrast imaging and urinary cytology alone were disease free compared with 61 (81.3%) of 75 patients who underwent ureteroscopic biopsy before nephroureterectomy (P = 0.18). The mean time from biopsy to nephroureterectomy for these 75 patients was 28 days, and the mean follow-up after nephroureterectomy was 40.1 months. Finally, 10 (83.3%) of 12 patients who underwent ureteroscopic biopsy and laser tumor ablation before nephroureterectomy were disease free at a mean follow-up of 37.2 months. The mean time from ureteroscopic biopsy to nephroureterectomy in this group was 196 days. No significant difference was found in the postoperative disease status between patients undergoing nephroureterectomy after ablation and those who proceeded to nephroureterectomy after endoscopic biopsy or those who did not undergo ureteroscopy before nephroureterectomy (P = 0.16)., Conclusions: Ureteroscopy with biopsy and/or tumor ablation before nephroureterectomy did not adversely affect the postoperative disease status.

Objectives: To estimate the incidence of prostate cancer among African-American men and Caribbean immigrants to the United States, to assess the applicability of large-scale prostate screening trials to a community screening program, and to recruit unscreened men., Methods: African-American and Caribbean-American men were targeted with a community-based prostate cancer screening program in Jamaica, New York. Serum prostate-specific antigen determination and digital rectal examination were used to determine abnormal findings. The incidence of an abnormal screening examination was used to project the incidence of prostate cancer, which was compared with that in other reported trials., Results: The projected incidence of prostate cancer among African-Americans and Caribbean-Americans older than 50 years was 8% and 7%, respectively, similar to that reported in other trials of African-American men. The projected incidence of prostate cancer in Caribbean-American men aged 40 to 49 years was 1%, the same as the high rate reported among Caribbean men. As in other trials, a family history of prostate cancer and age were strong predictors of abnormal findings. Of the recruited men older than 50 years, 58% had never been screened compared with 42% nationally., Conclusions: Large population-based screening trials have identified ethnic groups at high risk of prostate cancer. This trial detected high rates of abnormal screening findings by targeting ethnicity. The incidence of an abnormal examination was high in Caribbean-American men younger than 50 years old. Finally, this trial successfully recruited underscreened men.

Objectives: To evaluate the expression of the androgen receptor (AR) in transitional cell carcinoma (TCC) of the bladder, and to assess whether its expression correlated with pathologic tumor stage. TCC of the bladder is three times more common in males than in females. The origin of this sex difference in incidence is unknown., Methods: We evaluated tumor specimens from 49 consecutive patients treated for TCC of the bladder at our institution between July 2002 and June 2003. Immunohistochemistry was performed using a monoclonal mouse anti-AR antibody on paraffin-embedded tissue sections of tumors obtained from transurethral resection, radical cystectomy, or resection of metastases. Specimens were assessed for AR expression, and, in tumors that demonstrated AR staining, the percentage of nuclei that stained positive was recorded., Results: Of the 49 tumors, 26 (53.1%) expressed the AR. The percentage of tumors that expressed the AR decreased with increasing pathologic stage, from 88.9% of pTa lesions to 0% of pT3 tumors. Overall, 75% of superficial tumors (pTa + pT1 + carcinoma in situ) expressed the AR compared with 21.4% of invasive tumors (pT2 + pT3; P = 0.002). In addition, among AR-expressing tumors, the mean percentage of nuclei that stained positive for the AR was significantly greater in pTa tumors (62.5%) than in pT1 (31%) or pT2 (20%) tumors (P = 0.005)., Conclusions: We found a decrease in AR protein expression in tumors with increased pathologic stage. Our data suggest that the loss of AR expression is associated with invasive bladder cancer.

Objectives: To evaluate the effect of laparoscopy on practice patterns at a single institution in the treatment of renal cell carcinoma. Many now regard laparoscopic radical nephrectomy (LRN) as a standard of care in the management of localized renal cell carcinoma. As laparoscopy becomes more prevalent in the urologic community, practice patterns are changing., Methods: We analyzed the renal cancer surgical database at the Weill Medical College of Cornell University from 1997 to 2002. We compared three groups, including open radical nephrectomy (ORN), open partial nephrectomy (OPN), and LRN., Results: A total of 222 consecutive renal surgeries done for presumed malignancy were performed from 1997 to 2002. A total of 194 were assessable. Of these, 63 were OPNs, 51 were ORNs, and 80 were LRNs. When analyzed over time, during the latter half of 2000, 89% of all LRNs were performed on tumors less than 4 cm in size. More recently, in 2002, only 42% of LRNs were performed for tumors 4 cm or less in size. From 1997 to 2000, 30% of all OPNs were done on tumors greater than 4 cm compared with 28% from 2000 to 2002. Of 30 OPNs performed from 1997 to 2000, 21 (70%) were performed on small (4 cm or less) tumors compared with 24 (73%) of 33 from 2000 to 2002., Conclusions: From 2000 to 2002, the percentage of tumors less than 4 cm that were treated with LRN has increased with time. In the ORN cohort, the percentage of nephrectomies performed on small tumors (less than 4 cm) has decreased with time, and the trends in the OPN group have remained relatively stable. As an institution becomes more comfortable with laparoscopic techniques, technological concerns are likely to play less of a role in determining treatment algorithms among treating urologists.

Objectives: Expression of the active Met receptor tyrosine kinase causes tumor metastasis in animal models. To begin to analyze whether Met expression might be related to the spread of prostate cancer cells, we investigated whether its expression correlates with prostate-specific antigen recurrence and whether its expression depends on the site of metastasis., Methods: Ninety radical prostatectomy specimens with a Gleason sum of 6 or 7 and 86 specimens of bone, lymph node, and soft-tissue metastasis were immunohistochemically stained for Met, and a semiquantitative scoring system for Met in heterogeneously positive prostate cancers was applied. Met protein in prostate cancer cell lines was measured by Western blotting., Results: With the exception of two lymph node metastases, all metastases and 51% of the primary prostate cancers expressed Met. Moreover, the bone metastases expressed significantly more Met than did the lymph node metastases. However, in prostate cancer with a Gleason sum of 6 or 7, Met was not a prognostic marker for prostate-specific antigen recurrence. In prostate cancer cell lines, Met expression correlated inversely with expression of the androgen receptor., Conclusions: The high expression of the Met receptor tyrosine kinase in bone metastasis renders Met a promising target for nuclear imaging and treatment of metastatic prostate cancer.