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Purpose: Limited high-quality studies have compared robot-assisted laparoscopic prostatectomy (RALP) vs open retropubic radical prostatectomy. We sought to compare their postoperative outcomes in a randomized setting., Materials and Methods: In a single center, 354 men with newly diagnosed prostate cancer were assessed for eligibility; 342 were randomized (1:1). The primary outcome was 90-day complication rates. Functional outcomes and quality of life were assessed over 18 months, and oncological outcomes, biochemical recurrence-free survival, and additional treatment over 36 months., Results: From 2014 to 18, 327 patients underwent surgery (retropubic radical prostatectomy = 156, RALP = 171). Complications occurred in 27 (17.3%) vs 19 (11.1%; P = .107). Patients undergoing RALP experienced lower median bleeding (250.0 vs 719.5 mL; P < .001) and shorter hospitalization time. Urinary EPIC (Expanded Prostate Cancer Index Composite) median scores were better for RALP over 18 months, with higher continence rate at 3 months (80.5% vs 64.7%; P = .002), 6 months (90.1% vs 81.6%; P = .036) and 18 months (95.4% vs 78.8%; P < .001). Sexual EPIC and Sexual Health Inventory for Men median scores were higher with RALP up to 12 months, while the potency rate was superior at 3 months (23.9% vs 5.3%; P = .001) and 6 months (30.6% vs 6.9%; P < .001). Quality of life over the 18 months and oncological outcomes over 36 months were not significantly different between arms., Conclusions: Complications at 90 days were similar. RALP showed superior sexual outcomes at 1 year, improved urinary outcomes at 18 months, and comparable oncological outcomes at 36 months., Trial Registration: Prospective Analysis of Robot-Assisted Surgery; NCT02292914. https://clinicaltrials.gov/ct2/show/NCT02292914?cond=NCT02292914&draw=2&rank=1.

Introduction: Non-metastatic, castration-resistant prostate cancer (nmCRPC) is an important clinical stage of prostate cancer, prior to morbidity and mortality from clinical metastases. In particular, the introduction of novel androgen-receptor signaling inhibitors (ARSi) has changed the therapeutic landscape in nmCRPC. Given recent developments in this field, we update our recommendations for the management of nmCRPC., Methods: A panel of 51 invited medical oncologists and urologists convened in May of 2021 with the aim of discussing and providing recommendations regarding the most relevant issues concerning staging methods, antineoplastic therapy, osteoclast-targeted therapy, and patient follow-up in nmCRPC. Panel members considered the available evidence and their practical experience to address the 73 multiple-choice questions presented., Results: Key recommendations and findings include the reliance on prostate-specific antigen doubling time for treatment decisions, the absence of a clear preference between conventional and novel (i.e., positron-emission tomography-based) imaging techniques, the increasing role of ARSis in various settings, the general view that ARSis have similar efficacy. Panelists highlighted the slight preference for darolutamide, when safety is of greater concern, and a continued need to develop high-level evidence to guide the intensity of follow-up in this subset of prostate cancer., Discussion: Despite the limitations associated with a consensus panel, the topics addressed are relevant in current practice, and the recommendations can help practicing clinicians to provide state-of-the-art treatment to patients with nmCRPC in Brazil and other countries with similar healthcare settings., (Copyright © 2022. Published by Elsevier Inc.)

Purpose: To generate and present the survey results on critical issues relevant to screening, diagnosis, and staging tools for prostate cancer (PCa) focused on developing countries., Methods: A total of 36 of 300 questions concern the main areas of interest of this paper: (1) screening, (2) diagnosis, and (3) staging for various risk levels of PCa in developing countries. A panel of 99 international multidisciplinary cancer experts voted on these questions to create recommendations for screening, diagnosing, and staging tools for PCa in areas of limited resources discussed in this manuscript., Results: The panel voted publicly but anonymously on the predefined questions. Each question was deemed consensus if 75% or more of the full panel had selected a particular answer. These answers are based on panelist opinion not a literature review or meta-analysis. For questions that refer to an area of limited resources, the recommendations consider cost-effectiveness and the possible therapies with easier and greater access. Each question had five to seven relevant answers including two nonanswers. The results were tabulated in real time., Conclusion: The voting results and recommendations presented in this document can be used by physicians to support the screening, diagnosis, and staging of PCa in areas of limited resources. Individual clinical decision making should be supported by available data; however, as guidelines for screening, diagnosis, and staging of PCa in developing countries have not been developed, this document will serve as a point of reference when confronted with this disease., Competing Interests: Rodrigo de Morais HanriotSpeakers' Bureau: AstraZeneca, Varian Medical Systems, Bristol Myers Squibb, Takeda, Roche Alvaro Sadek SarkisEmployment: Roche (I)Leadership: FerringHonoraria: Ferring, Merck Sharp & Dohme, Genomic Health, Astellas PharmaConsulting or Advisory Role: FerringSpeakers' Bureau: FerringResearch Funding: FerringTravel, Accommodations, Expenses: Ferring Bruno Santos BenignoSpeakers' Bureau: Janssen-Cilag Amr NowierResearch Funding: Astellas Pharma Ari Adamy JrSpeakers' Bureau: Janssen-Cilag, Astellas Pharma, Bayer, PfizerTravel, Accommodations, Expenses: Janssen-Cilag, Astellas Pharma Eduardo Franco CarvalhalHonoraria: JanssenNo other potential conflicts of interest were reported.

The objective of this study is to report the first multicentric Brazilian series and learning curve of robotic radical cystectomy (RARC) with related intra- and postoperative outcomes. We retrospectively analyzed 37 RARC prospectively collected at four different centers in Brazil, from 2013 to 2019. We analyzed the patient's demographics, pathological tumor, and nodal status, as well as intra- and postoperative outcomes. Statistical analysis was performed with the IBM (SPSS version 25) software. Overall, 86% were male, and the median age was 69 years. 83% had muscle-invasive bladder cancer, and 17% a high-grade, recurrent non-muscle-invasive tumor. The median operative time was 420 min with 300 min as console time. Median blood loss was 350 ml and transfusion rate was 10%. In 68% of the cases, we performed an intracorporeal Bricker urinary diversion, 24% intracorporeal neobladder, and 8% ureterostomy. Six patients (16%) had a Clavien 1-2, 8% had Clavien 3, 2.5% had a Clavien 4, and 5% had Clavien 5. The median length of hospital stay was 7 days. The final pathological exam pointed out pT0 in 16%, pT1 in 8%, pT2 in 32%, ≥ pT3 in 27%, and 16% pTis. 95% had negative surgical margins. The survival at 30, 90, and 180 days was 98%, 95%, and 95%, respectively. To our knowledge, this is the first multicentric series of RARC reporting the learning curve in Brazil; even if still representing a challenging procedure, RARC could be safely and effectively faced by experienced surgeons at centers with high volumes of robotic surgery.

Purpose of Review: The objective of the current article is to promote a literature revision of the relationship between the prevention of intraepithelial neoplasms (PeIN) and invasive penile cancer, and human papillomavirus (HPV) vaccination, aiming to enumerate the pros and cons of immunization., Recent Findings: The immunization against the HPV is sufficiently safe and many countries have incorporated the vaccine to their immunization calendar. Compared with men, the sampling size and the evidence quality of scientific researches among the female population are more robust. Some randomized and nonrandomized studies suggest that vaccination reduces the incidence of genital warts and no PeIN and penile cancer cases were developed in the vaccinal group. However, 70% of patients can evolve with the neoplasia despite having been immunized and even among HPV infected patients, only 1% will develop cancer., Summary: The studies about vaccination against HPV and prevention on penile cancer are conflicting and the main academic urology societies still have not incorporated vaccination of men in their guidelines. Future studies are necessary to confirm the efficiency and cost-benefit of the vaccine in men to prevent intraepithelial neoplasms and invasive penile cancer.

Background: The purpose of this study was to compare the efficacy of 2 bacillus Calmette-Guérin (BCG) strains, BCG-Tice and BCG-Moreau, in the treatment of non-muscle-invasive bladder cancer (NMIBC)., Materials and Methods: We retrospectively reviewed clinical data from patients treated with BCG for NMIBC at 3 academic centers. Inverse probability of treatment weighting (IPTW)-adjusted Kaplan-Meier curves and Cox proportional hazards regression analyses were used to compare recurrence-free (RFS) and progression-free survival (PFS) of patients in the 2 treatment groups. In addition, we performed exploratory analyses of treatment effect according to the receipt of adequate BCG treatment, high-risk disease, age, gender, smoking status, pathologic stage, and pathologic grade., Results: A total of 321 (48.6%) patients were treated with BCG-Tice and 339 (51.4%) with BCG-Moreau. IPTW-adjusted Cox proportional hazard regression analysis did not show a difference in RFS (hazard ratio, 0.88; 95% confidence interval, 0.56-1.38; P = .58) or PFS (hazard ratio, 0.55; 95% confidence interval, 0.25-1.21, P = .14) between BCG-Tice and BCG-Moreau. On subgroup analyses, we could not identify an association of BCG strain with outcomes., Conclusions: There was no difference in RFS and PFS between BCG-Tice and BCG-Moreau strains in the adjuvant treatment of NMIBC. However, we confirmed the importance of maintenance therapy for achieving a sustainable response in patients with intermediate- and high-risk NMIBC., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Serum cholinesterase (ChE) a serine hydrolase that catalyses the hydrolysis of esters of choline, is involved in cellular proliferation and differentiation, therefore affecting carcinogenesis. The aim of this study was to understand the prognostic role of preoperative serum ChE in patients with radiation-recurrent prostate cancer (CaP) treated with salvage radical prostatectomy (SRP)., Material and Methods: This retrospective study included 214 patients with radiation-recurrent CaP treated with SRP from January 2007 to December 2015 at 5 academic centers. Patients were considered with abnormal/decreased ChE levels if <5 kU/l. Biochemical recurrence-free and metastases-free (MFS) survival analyses were performed., Results: Median serum ChE level was 6.9 (interquartile range) 6-7.7) kU/l. Serum ChE level (<5 kU/l) was decreased in 25 (11.7%) patients. Decreased serum ChE level was associated with lower body mass index (P = 0.006) and metastasis to lymph nodes (P = 0.004). In multivariable analysis, continuous ChE was an independent predictor of MFS (hazard ratio [HR] 0.48, confidence interval [CI] 0.33-0.71, P < 0.001), overall survival (HR 0.68, CI 0.48-0.96, P = 0.03) and cancer-specific survival (HR 0.41, CI 0.2-0.84, P = 0.01). Serum ChE improved the C-index (by 2.54%) to 87.8% for prediction of overall survival and (by 3%) to 92% for prediction of MFS., Conclusion: Preoperative serum ChE is associated with the development of metastasis in patients with radiation-recurrent CaP who underwent SRP. The biological underpinning of this association with the biological and clinical aggressiveness of CaP needs to be further elucidated., (Copyright © 2018. Published by Elsevier Inc.)

Introduction: The purpose of the present study was to investigate the association of smoking with biochemical recurrence (BCR) and metastasis in radiation-recurrent prostate cancer (PCa) patients undergoing salvage radical prostatectomy (SRP)., Patients and Methods: A total of 214 patients treated with SRP for radiation-recurrent PCa in 5 tertiary referral centers were included from January 2007 to December 2015. Kaplan-Meier analyses were used to assess the time to BCR and metastasis. Pre- and postoperative multivariable Cox proportional hazard regression models were fitted., Results: Overall, 120 (56.1%), 49 (22.9%), and 45 (21%) patients were never, former, and current smokers, respectively. Low-, medium-, and high-cumulative smoking exposure was registered in 59.8%, 16.4%, and 23.8% of cases, respectively. Patients with high cumulative smoking exposure had a significantly greater rate of a pathologic Gleason score of ≥ 8 (P = .01) and extracapsular extension (P = .004). Smoking status, cumulative smoking exposure, intensity, and duration were significantly associated with BCR-free survival (P < .001 for all). Smoking status, cumulative smoking exposure, and smoking intensity were significantly associated with metastasis-free survival (P = .03 for all). High cumulative smoking exposure was independently associated with BCR in both pre- (hazard ratio, 2.23; P = .001) and postoperative (hazard ratio, 1.64; P = .04) multivariable models adjusted for the effects of established clinicopathologic features. Smoking cessation did not affect either BCR- or metastasis-free survival (P = .56 and P = .40, respectively)., Conclusion: High cumulative smoking exposure was associated with the biologic and clinical aggressiveness of PCa in patients treated with SRP for radiation-recurrent disease. Smoking is a modifiable risk factor that detrimentally affected the outcomes, even in patients with advanced PCa., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Purpose: Upper-tract urothelial carcinoma (UTUC) is a relatively uncommon disease with limited available evidence on specific topics. The purpose of this article was to review the previous literature to summarize the current knowledge about UTUC epidemiology, diagnosis, preoperative evaluation and prognostic assessment., Methods: Using MEDLINE, a non-systematic review was performed including articles between January 2000 and February 2016. English language original articles, reviews and editorials were selected based on their clinical relevance., Results: UTUC accounts for 5-10 % of all urothelial cancers, with an increasing incidence. UTUC and bladder cancer share some common risk factors, even if they are two different entities regarding practical, biological and clinical characteristics. Aristolochic acid plays an important role in UTUC pathogenesis in certain regions. It is further estimated that approximately 10 % of UTUC are part of the hereditary non-polyposis colorectal cancer spectrum disease. UTUC diagnosis remains mainly based on imaging and endoscopy, but development of new technologies is rapidly changing the diagnosis algorithm. To help the decision-making process regarding surgical treatment, extent of lymphadenectomy and selection of neoadjuvant systemic therapies, predictive tools based on preoperative patient and tumor characteristics have been developed., Conclusions: Awareness regarding epidemiology, diagnosis, preoperative evaluation and prognostic assessment changes is essential to correctly diagnose and manage UTUC patients, thereby potentially improving their outcomes.

Objective: To identify factors associated with survival after palliative urinary diversion (UD) for patients with malignant ureteric obstruction (MUO) and create a risk-stratification model for treatment decisions., Patients and Methods: We prospectively collected clinical and laboratory data for patients who underwent palliative UD by ureteric stenting or percutaneous nephrostomy (PCN) between 1 January 2009 and 1 November 2011 in two tertiary care university hospitals, with a minimum 6-month follow-up. Inclusion criteria were age >18 years and MUO confirmed by computed tomography, ultrasonography or magnetic resonance imaging. Factors related to poor prognosis were identified by Cox univariable and multivariable regression analyses, and a risk stratification model was created by Kaplan-Meier survival estimates at 1, 6 and 12 months, and log-rank tests., Results: The median (range) survival was 144 (0-1084) days for the 208 patients included after UD (58 ureteric stenting, 150 PCN); 164 patients died, 44 (21.2%) during hospitalisation. Overall survival did not differ by UD type (P = 0.216). The number of events related to malignancy (≥4) and Eastern Cooperative Oncology Group (ECOG) index (≥2) were associated with short survival on multivariable analysis. These two risk factors were used to divide patients into three groups by survival type: favourable (no factors), intermediate (one factor) and unfavourable (two factors). The median survival at 1, 6, and 12 months was 94.4%, 57.3% and 44.9% in the favourable group; 78.0%, 36.3%, and 15.5% in the intermediate group; and 46.4%, 14.3%, and 7.1% in the unfavourable group (P < 0.001)., Conclusions: Our stratification model may be useful to determine whether UD is indicated for patients with MUO., (© 2014 The Authors BJU International © 2014 BJU International Published by John Wiley & Sons Ltd.)

Background: Bacillus Calmette-Guerin (BCG) is the standard of care for adjuvant intravesical instillation therapy for intermediate- and high-risk non-muscle invasive bladder cancer (NMIBC) after complete transurethral resection. Increasing evidence suggests that there are marked differences in outcomes according to BCG substrains. BCG-Moreau was recently introduced to the European market to cover the issue of BCG shortage, but there are little data regarding the oncologic efficacy., Methods: We retrospectively analyzed 295 consecutive patients, who received adjuvant intravesical instillation therapy with BCG-Moreau for intermediate- and high-risk NMIBC between October 2007 and April 2013 at a single institution. The end points of this study were time to first recurrence and progression to muscle-invasive disease., Results: Median age was 66 years (interquartile range 59-74, mean 65.9 years). According to the EAU risk group, 76 patients presented with intermediate-risk and 219 patients with high-risk NMIBC. The 5-year recurrence-free survival and progression-free survival rate was 64.8% (95% CI 52.8-74.4) and 81.4% (95% CI 65.2-90.2), respectively., Conclusions: BCG-Moreau is an effective substrain for adjuvant instillation therapies of NMIBC, and outcomes appear to be comparable to series using other substrains. During worldwide shortage of BCG-TICE, Connaught and RIVM, BCG-Moreau may serve as an equally effective alternative., (© 2015 S. Karger AG, Basel.)

Purpose: Subclassification of nodal stage may have prognostic value in men with lymph node metastasis at radical prostatectomy. We explored the role of extranodal extension, size of the largest metastatic lymph node and the largest metastasis, and lymph node density as predictors of biochemical recurrence., Materials and Methods: We reviewed pathological material from 261 patients with node positive prostate cancer. We examined the predictive value when adding the additional pathology findings to a base model including extraprostatic extension, seminal vesicle invasion, radical prostatectomy Gleason score, prostate specific antigen and number of positive lymph nodes using the Cox proportional hazards regression and Harrell concordance index., Results: The median number of lymph nodes removed was 14 (IQR 9, 20) and the median number of positive lymph nodes was 1 (IQR 1, 2). At a median followup of 4.6 years (IQR 3.2, 6.0) 155 of 261 patients experienced biochemical recurrence. The mean 5-year biochemical recurrence-free survival rate was 39% (95% CI 33-46). Median diameter of the largest metastatic lymph node was 9 mm (IQR 5, 16). On Cox regression radical prostatectomy specimen Gleason score (greater than 7 vs 7 or less), number of positive lymph nodes (3 or greater vs 1 or 2), seminal vesicle invasion and prostate specific antigen were associated with significantly increased risks of biochemical recurrence. On subset analysis metastasis size significantly improved model discrimination (base model Harrell concordance index 0.700 vs 0.655, p = 0.032)., Conclusions: Our study confirms that the number of positive lymph nodes is a predictor of biochemical recurrence in men with node positive disease. The improvement in prognostic value of measuring the metastatic focus warrants further investigation., (Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purposes: To describe the differential tissue expression of tumor-associated trypsin inhibitor (TATI) in normal bladder urothelium, primary urothelial carcinoma of the bladder (UCB) and metastatic UCB and to assess the association of TATI expression with molecular markers commonly altered in UCB and clinical outcomes after radical cystectomy., Methods: Slides from eight cystectomy patients without cancer, 191 radical cystectomy patients, 20 lymph nodes without metastasis and 40 lymph nodes with UCB were stained. Tissue expression of TATI, cyclin E1, cyclin D1, p53, p21, p27, pRB, Ki-67, Bcl-2, Caspase-3, Survivin and Cyclooxigenase-2 was measured in a tissue microarray. Cancer-specific and recurrence-free survival after radical cystectomy was recorded., Results: TATI was expressed in 100% of patients without cancer, while 71% of radical cystectomy specimens and 90% of lymph node metastases exhibited decreased or no TATI expression. In radical cystectomy specimens, TATI expression decreased with advancing pathologic stage (P < 0.001) and lymphovascular invasion (P = 0.055). In univariate analyses, but not in multivariable Cox proportional hazard regression analyses, decreased TATI expression was associated with increased probability of tumor recurrence and cancer-specific mortality. Decreased TATI expression was correlated with altered expression of Cyclooxigenase-2 (P = 0.005), p21 (P = 0.035) and Ki-67 (P = 0.004)., Conclusions: We found that normal urothelium expresses TATI and that TATI expression decreases with advancing tumor stage. While there was no prognostic benefit to TATI when adjusted for standard clinicopathologic features, it seems to play an important biologic role in UCB pathogenesis and invasion. Its association with markers involved in the cell cycle, proliferation and inflammation serves as hypothesis for molecular interactions.

Purpose: We determined the frequency and distribution of metastases to pelvic lymph nodes in a contemporary American radical prostatectomy series., Materials and Methods: In 642 consecutive patients with clinically localized prostate cancer treated by a single surgeon between 2002 and 2009 pelvic lymph nodes were removed and submitted to the pathologist in separate packets (external iliac, obturator and hypogastric). We assessed the total number of nodes and the number with metastases in each packet., Results: Complete pathological information was available for 427 patients, who had a median of 16 lymph nodes removed. Of the patients 35 (8.2%) had lymph node metastases, including 1.7% with low, 8.6% with intermediate and 23.9% with high risk cancer. Of those with nodal metastases 24 (69%) had positive lymph nodes in only 1 of the 3 areas, including the external iliac in 4 (11%), the obturator in 9 (26%) and the hypogastric in 11 (31%). Only 37% of the patients had positive nodes only in the external iliac area above the obturator nerve while 60% and 49% had at least 1 positive node in the obturator and the hypogastric area, respectively. Of the patients 80% had only 1 (49%) or 2 (31%) positive nodes., Conclusions: In contemporary American patients with clinically localized prostate cancer lymph node metastases were found more often and frequently exclusively in the obturator and hypogastric areas than in the external iliac area. Pelvic lymph node dissection limited to the external iliac area above the obturator nerve would identify and remove lymph node metastases in only a third of the patients with positive nodes found at full pelvic lymph node dissection., (Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Context: Prostate cancer (PCa) recurrence following definitive radiation therapy (RT) remains a vexing challenge for the practicing physician. Salvage radical prostatectomy (SRP) has not been recognized yet as a valuable therapeutic option., Objective: We critically analyzed the currently available evidence on SRP as to patient selection, predictive oncologic factors, surgical technique, cancer control, surgical complications, functional outcomes, and comparison to other salvage therapies., Evidence Acquisition: A systematic review of the literature was performed in June 2011 using the Medline, Embase, and Web of Science databases, limiting the review to English-language articles published between January 1980 and June 2011. All authors reviewed the list of references and added papers relevant to the topic of the review prior to the analysis. The panel selected 40 articles according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria., Evidence Synthesis: Positive surgical margins in SRP varied from 43% to 70% in earlier publications versus 0-36% in recent publications, and pathologic organ-confined disease (OCD) was found in 22-53% versus 44-73% in earlier versus recent publications. Biochemical recurrence-free probability after SRP ranged from 47% to 82% at 5 yr and from 28% to 53% at 10 yr. Cancer-specific survival (CSS) and overall survival varied from 70% to 83% and 54% to 89% at 10 yr. Pre-SRP prostate-specific antigen value and prostate biopsy Gleason score were the strongest prognostic risk factors for progression-free survival, OCD, and CSS. Open, laparoscopic, and robotic techniques were shown to be feasible in the hands of experienced surgeons. The most frequent complications included anastomotic stricture (7-41%) followed by rectal injury (0-28%). Major complications (modified Clavien classification grade 3-5) varied from 0% to 25%. Most complications were less frequent in more recent series, except for anastomotic stricture. The majority of patients had erectile dysfunction prior to SRP (50-91%) and 80-100% after SRP. Urinary continence ranged from 21% to 90% after surgery. Limitations of this review include the absence of prospective studies and lack of comparative analyses between SRP and other therapies., Conclusions: In selected patients with confirmed, localized, radiation-recurrent PCa, SRP may effectively promote durable cancer control with acceptable associated surgical morbidity and variable functional recovery., (Copyright © 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Objective: To create a preoperative multivariable model to identify patients at risk of muscle-invasive (pT2+) upper tract urothelial carcinoma (UTUC) and/or non-organ confined (pT3+ or N+) UTUC (NOC-UTUC) who potentially could benefit from radical nephroureterectomy (RNU), neoadjuvant chemotherapy and/or an extended lymph node dissection., Patients and Methods: We retrospectively analysed data from 324 consecutive patients treated with RNU between 1995 and 2008 at a tertiary cancer centre. Patients with muscle-invasive bladder cancer were excluded, resulting in 274 patients for analysis. Logistic regression models were used to predict pT2+ and NOC-UTUC. Pre-specified predictors included local invasion (i.e. parenchymal, renal sinus fat, or periureteric) on imaging, hydronephrosis on imaging, high-grade tumours on ureteroscopy, and tumour location on ureteroscopy. Predictive accuracy was measured by the area under the curve (AUC)., Results: The median follow-up for patients without disease recurrence or death was 4.2 years. Overall, 49% of the patients had pT2+, and 30% had NOC-UTUC at the time of RNU. In the multivariable analysis, only local invasion on imaging and ureteroscopy high grade were significantly associated with pathological stage. AUC to predict pT2+ and NOC-UTUC were 0.71 and 0.70, respectively., Conclusions: We designed a preoperative prediction model for pT2+ and NOC-UTUC, based on readily available imaging and ureteroscopic grade. Further research is needed to determine whether use of this prediction model to select patients for conservative management vs RNU, neoadjuvant chemotherapy, and/or extended lymphadenectomy will improve patient outcomes., (© 2011 THE AUTHORS. BJU INTERNATIONAL © 2011 BJU INTERNATIONAL.)

Objective: • To evaluate feasibility, safety and oncological efficacy of salvage laparoscopic radical prostatectomy for pathology-proven biochemical recurrence after primary radiation therapy or cryotherapy for prostate cancer., Materials and Methods: • This retrospective pilot study examined 15 patients from 2004 to 2010 with biochemical recurrence after external beam radiation therapy (N= 8), brachytherapy (N= 6) or cryotherapy (N= 1). • Patients were treated with salvage laparoscopic radical prostatectomy (11 conventional, four robotic-assisted) with bilateral pelvic dissection., Results: • Median duration of surgery was 235 min. None of the following occurred: conversion to open surgery, transfusion, urethrovesical stenosis or perioperative or postoperative mortality. One patient presented with a rectal injury, repaired using uninterrupted sutures and a colostomy. One patient had anastomotic leak treated with prolonged Foley catheterization. • Pathological stage was pT2a in three, pT2b in three, pT3a in four, pT3b in three and pT4 in two patients; two patients had nodal metastasis. Within an 8-month median follow-up, 11 patients were disease-free and three had persistent postoperative prostate-specific antigen (PSA) elevation; the remaining patient experienced PSA recurrence after 21 months. • Seven patients achieved continence (no pads) by 8.4 months (median), one patient manifested severe incontinence corrected by implanting an artificial sphincter, and seven patients with a 12.6-month mean follow-up continued to need one or two pads per day. • Erectile dysfunction was present in five patients before surgery and in 14 patients after surgery., Conclusion: • Salvage laparoscopic radical prostatectomy seems to offer a safe therapeutic alternative for patients failing primary radiation or cryotherapy. However, larger studies with longer-term data are required., (© 2010 THE AUTHORS. BJU INTERNATIONAL © 2010 BJU INTERNATIONAL.)

Background: Oncologic outcomes in men with radiation-recurrent prostate cancer (PCa) treated with salvage radical prostatectomy (SRP) are poorly defined., Objective: To identify predictors of biochemical recurrence (BCR), metastasis, and death following SRP to help select patients who may benefit from SRP., Design, Setting, and Participants: This is a retrospective, international, multi-institutional cohort analysis. There was a median follow-up of 4.4 yr following SRP performed on 404 men with radiation-recurrent PCa from 1985 to 2009 in tertiary centers., Intervention: Open SRP., Measurements: BCR after SRP was defined as a serum prostate-specific antigen (PSA) ≥ 0.1 or ≥ 0.2 ng/ml (depending on the institution). Secondary end points included progression to metastasis and cancer-specific death., Results and Limitations: Median age at SRP was 65 yr of age, and median pre-SRP PSA was 4.5 ng/ml. Following SRP, 195 patients experienced BCR, 64 developed metastases, and 40 died from PCa. At 10 yr after SRP, BCR-free survival, metastasis-free survival, and cancer-specific survival (CSS) probabilities were 37% (95% confidence interval [CI], 31-43), 77% (95% CI, 71-82), and 83% (95% CI, 76-88), respectively. On preoperative multivariable analysis, pre-SRP PSA and Gleason score at postradiation prostate biopsy predicted BCR (p = 0.022; global p < 0.001) and metastasis (p = 0.022; global p < 0.001). On postoperative multivariable analysis, pre-SRP PSA and pathologic Gleason score at SRP predicted BCR (p = 0.014; global p < 0.001) and metastasis (p < 0.001; global p < 0.001). Lymph node involvement (LNI) also predicted metastasis (p = 0.017). The main limitations of this study are its retrospective design and the follow-up period., Conclusions: In a select group of patients who underwent SRP for radiation-recurrent PCa, freedom from clinical metastasis was observed in >75% of patients 10 yr after surgery. Patients with lower pre-SRP PSA levels and lower postradiation prostate biopsy Gleason score have the highest probability of cure from SRP., (Copyright © 2011 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Objective: Cigarette smoking is the main risk factor for bladder cancer development. Among the mediators of this effect of smoking is nuclear factor-kappa B. Curcumin suppresses cellular transformation by downregulating the activity of nuclear factor-kappa B. Prima-1 is a compound that induces apoptosis in human tumor cells, restoring the function of mutant p53. Our study aimed to evaluate the effects of curcumin and prima-1 in an animal model of bladder cancer., Methods: Tumor implantation was achieved in six- to eight-week-old female C57BL/6 mice by introducing MB49 bladder cancer cells into the bladder. Intravesical treatment with curcumin and Prima-1 was performed on days 2, 6, 10, and 14. On day 15, the animals were sacrificed. Immunohistochemistry was used to determine the expression of cyclin D1, Cox-2, and p21. Cell proliferation was examined using PCNA., Results: Animals treated with curcumin exhibited a higher degree of necrosis than animals in other groups. Immunohistochemistry showed reduced expression of cyclin D1 in the curcumin-treated group. All of the cells in mice treated with curcumin were p21 positive, suggesting that the p53 pathway is induced by this compound. Prima-1 did not induce any change in tumor size, necrosis, cell proliferation, or the expression of proteins related to the p53 pathway in this animal model., Conclusion: Curcumin showed activity in this animal bladder cancer model and probably acted via the regulation of nuclear factor-kappa B and p53. Therefore, curcumin is a good choice for the use in clinical trials to treat superficial bladder cancer as an alternative to bacillus Calmette-Guerin. In contrast, Prima-1 does not seem to have an effect on bladder cancer.

Purpose: The learning curve is a period in which the surgical procedure is performed with difficulty and slowness, leading to a higher risk of complications and reduced effectiveness due the surgeon's inexperience. We sought to analyze the residents' learning curve for open radical prostatectomy (RP) in a training program., Materials and Methods: We conducted a prospective study from June 2006 to January 2008 in the academic environment of the University of Sao Paulo. Five residents operated on 184 patients during a four-month rotation in the urologic oncology division, mentored by the same physician assistants. We performed sequential analyses according to the number of surgeries, as follows: ≤ 10, 11 to 19, 20 to 28, and ≥ 29., Results: The residents performed an average of 37 RP each. The average psa was 9.3 ng/mL and clinical stage T1c in 71% of the patients. The pathological stage was pT2 (73%), pT3 (23%), pT4 (4%), and 46% of the patients had a Gleason score 7 or higher. In all surgeries, the average operative time and estimated blood loss was 140 minutes and 488 mL. Overall, 7.2% of patients required blood transfusion, and 23% had positive surgical margins., Conclusion: During the initial RP learning curve, we found a significant reduction in the operative time; blood transfusion during the procedures and positive surgical margin rate were stable in our series.

Background: Open radical nephroureterectomy (ORN) is the current standard of care for upper tract urothelial carcinoma (UTUC), but laparoscopic radical nephroureterectomy (LRN) is emerging as a minimally invasive alternative. Questions remain regarding the oncologic safety of LRN and its relative equivalence to ORN., Objective: Our aim was to compare recurrence-free and disease-specific survival between ORN and LRN., Design, Setting, and Participants: We retrospectively analyzed data from 324 consecutive patients treated with radical nephroureterectomy (RN) between 1995 and 2008 at a major cancer center. Patients with previous invasive bladder cancer or contralateral UTUC were excluded. Descriptive data are provided for 112 patients who underwent ORN from 1995 to 2001 (pre-LRN era). Comparative analyses were restricted to patients who underwent ORN (n=109) or LRN (n=53) from 2002 to 2008. Median follow-up for patients without disease recurrence was 23 mo., Intervention: All patients underwent RN., Measurements: Recurrence was categorized as bladder-only recurrence or any recurrence (bladder, contralateral kidney, operative site, regional lymph nodes, or distant metastasis). Recurrence-free probabilities were estimated using Kaplan-Meier methods. A multivariable Cox model was used to evaluate the association between surgical approach and disease recurrence. The probability of disease-specific death was estimated using the cumulative incidence function., Results and Limitations: Clinical and pathologic characteristics were similar for all patients. The recurrence-free probabilities were similar between ORN and LRN (2-yr estimates: 38% and 42%, respectively; p=0.9 by log-rank test). On multivariable analysis, the surgical approach was not significantly associated with disease recurrence (hazard ratio [HR]: 0.88 for LRN vs ORN; 95% confidence interval [CI], 0.57-1.38; p=0.6). There was no significant difference in bladder-only recurrence (HR: 0.78 for LRN vs ORN; 95% CI, 0.46-1.34; p=0.4) or disease-specific mortality (p=0.9). This study is limited by its retrospective nature., Conclusions: Based on the results of this retrospective study, no evidence indicates that oncologic control is compromised for patients treated with LRN in comparison with ORN., (Copyright © 2010 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: The prognostic impact of primary tumor location on outcomes for patients with upper-tract urothelial carcinoma (UTUC) is still contentious., Objective: To test the association between tumor location and disease recurrence and cancer-specific survival (CSS) in patients treated with radical nephroureterectomy (RNU) for UTUC., Design, Setting, and Participants: Prospectively collected data were retrospectively reviewed from 324 consecutive patients treated with RNU between 1995 and 2008 at a single tertiary referral center. Patients who had previous radical cystectomy, preoperative chemotherapy, previous contralateral UTUC, or metastatic disease at presentation were excluded. This left 253 patients for analysis. Tumor location was categorized as renal pelvis or ureter based on the location of the dominant tumor. Recurrences in the bladder only, in nonbladder sites, and in any site were analyzed., Intervention: All patients were treated with RNU., Measurements: Recurrence-free survival and CSS probabilities were estimated using Kaplan-Meier and Cox regression analyses., Results and Limitations: Median follow-up for survivors was 48 mo. The 5-yr recurrence-free probability (including bladder recurrence) and CSS estimates were 32% and 78%, respectively. On multivariable analysis, pathologic stage was the only predictor for disease recurrence (p=0.01). Tumor location was not an independent predictor for recurrence (hazard ratio: 1.19; p=0.3), and there was no difference in the probability of disease recurrence between ureteral and renal pelvic tumors (p=0.18). On survival analysis, we also found no differences between ureteral and renal pelvic tumors on probability of CSS (p=0.2). On multivariate analysis, pathologic stage (p<0.0001) and nodal status (p=0.01) were associated with worse CSS. This study is limited by its retrospective nature., Conclusions: Our study did not show any differences in recurrence and CSS rates between patients with ureteral and renal pelvic tumors treated with RNU., (Copyright 2010 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Purpose: Bacillus Calmette-Guerin (BCG) continues to be employed as the most effective immunotherapy against superficial bladder cancer. We have developed an rBCG-S1PT strain that induces a stronger cellular immune response than BCG. This preclinical study was designed to test the potential of rBCG-S1PT as an immunotherapeutic agent for intravesical bladder cancer therapy., Materials and Methods: A tumor was induced in C57BL/6 mice after chemical cauterization of the bladder and inoculation of the tumor cell line MB49. Next, mice were treated by intravesical instillation with BCG, rBCG-S1PT, or PBS once a week for 4 weeks. After 35 days, the bladders were removed and weighed, Th1 (IL-2, IL-12, INOS, INF-gamma, TNF-alpha), and Th2 (IL-5, IL-6, IL-10, TGF-beta) cytokine mRNA responses in individual mice bladders were measured by quantitative real time PCR, and the viability of MB49 cells in 18-hour coculture with splenocytes from treated mice was assessed. In an equivalent experiment, animals were observed for 60 days to quantify their survival., Results: Both BCG and rBCG-S1PT immunotherapy resulted in bladder weight reduction, and rBCG-S1PT increased survival time compared with the control group. There were increases in TNF-alpha in the BCG treated group, as well as increases in TNF-alpha and IL-10 mRNA in the rBCG-S1PT group. The viability of MB49 cells cocultured with splenocytes from rBCG-S1PT-treated mice was lower than in both the BCG and control groups., Conclusions: rBCG-S1PT therapy improved outcomes and lengthened survival times. These results indicate that rBCG could serve as a useful substitute for wild-type BCG., (Copyright (c) 2010 Elsevier Inc. All rights reserved.)

Purpose: Differences in clinical outcome are still unclear between primary and secondary bladder carcinoma in situ. We compared the clinical outcomes of primary and secondary carcinoma in situ, and identified predictive factors., Materials and Methods: We retrospectively analyzed the records of 476 patients with high grade cTis, including 221 with primary and 255 with secondary carcinoma in situ, from 1990 to 2008 at a high volume cancer center after transurethral resection and intravesical bacillus Calmette-Guerin therapy. End points were time to progression to invasive disease (cT1 or higher) or radical cystectomy before progression, and progression to muscle invasive disease (cT2 or higher) or radical cystectomy before progression. We used Cox proportional hazards regression models., Results: Patients with primary carcinoma in situ responded significantly more within 6 months of bacillus Calmette-Guerin than those with secondary carcinoma in situ (65% vs 39%, p <0.001). In the primary vs secondary groups the 5-year cumulative incidence of progression to cT1 or higher was 43% (95% CI 36-51) vs 32% (95% CI 27-39) and for progression to cT2 or higher it was 17% (95% CI 12-23) vs 8% (95% CI 5-13). On multivariate analysis primary carcinoma in situ was significantly more likely to progress to cT1 or higher (HR 1.38, 95% CI 1.05-1.81, p = 0.020) and to cT2 or higher, or radical cystectomy (HR 1.72, 95% CI 1.27-2.33, p = 0.001). We found no significance for age, gender or response to bacillus Calmette-Guerin as outcome predictors. Median followup was 5.1 years., Conclusions: Patients presenting with primary carcinoma in situ have a worse outcome than those with secondary carcinoma in situ, suggesting a need to differentiate these 2 entities in the treatment decision process., (Copyright (c) 2010 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: We evaluated predictors of freedom from biochemical recurrence in patients with pelvic lymph node metastasis at radical prostatectomy., Materials and Methods: Of 207 patients with lymph node metastasis treated with radical prostatectomy and bilateral pelvic lymph node dissection 45 received adjuvant androgen deprivation therapy and 162 did not. Cox proportional hazards regression models were used to investigate predictors of biochemical recurrence after radical prostatectomy. Recurrence probability was estimated using the Kaplan-Meier method., Results: A median of 13 lymph nodes were removed. Of the patients 122 had 1, 44 had 2 and 41 had 3 or greater positive lymph nodes. Of patients without androgen deprivation therapy 103 had 1, 35 had 2 and 24 had 3 or greater positive lymph nodes while 69 experienced biochemical recurrence. Median time to recurrence in patients with 1, 2 and 3 or greater lymph nodes was 59, 13 and 3 months, respectively. Only specimen Gleason score and the number of positive lymph nodes were independent predictors of biochemical recurrence. Recurrence-free probability 2 years after prostatectomy in men without androgen deprivation with 1 positive lymph node and a prostatectomy Gleason score of 7 or less was 79% vs 29% in those with Gleason score 8 or greater and 2 or more positive lymph nodes., Conclusions: Prognosis in patients with lymph node metastasis depends on the number of positive lymph nodes and primary tumor Gleason grade. Of all patients with lymph node metastasis 80% had 1 or 2 positive nodes. A large subset of those patients had a favorable prognosis. Full bilateral pelvic lymph node dissection should be done in patients with intermediate and high risk cancer to identify those likely to benefit from metastatic node removal., (Copyright (c) 2010 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: The natural history of primary bladder carcinoma in situ has not been well described. We describe patterns of disease recurrence and progression, and identify clinical outcome predictors of primary carcinoma in situ after bacillus Calmette-Guerin therapy., Materials and Methods: We performed a retrospective analysis of 155 patients diagnosed with isolated primary high grade carcinoma in situ at a tertiary center from 1990 to 2008 who underwent transurethral resection followed by intravesical bacillus Calmette-Guerin therapy. The end points included time to disease recurrence, time to progression to invasive disease (cT1 or higher) or to muscle invasive disease (cT2 or higher), or early radical cystectomy. Predictors included gender, age, race, smoking history, presenting symptoms, carcinoma in situ pattern (focal, multiple or diffuse) and response to bacillus Calmette-Guerin., Results: A total of 155 patients received bacillus Calmette-Guerin therapy within 6 months. The 5-year cumulative incidence of progression to cT1 or higher was 45% (95% CI 37-55) and to cT2 or higher was 17% (95% CI 12-25) adjusting for the competing risk of radical cystectomy. Of 130 patients evaluated for response to bacillus Calmette-Guerin 81 (62%) were considered responders. Response to bacillus Calmette-Guerin was significantly associated with progression to cT1 or higher/radical cystectomy (HR 0.59, 95% CI 0.36-0.95, p = 0.029) and to cT2 or higher/radical cystectomy (HR 0.53, 95% CI 0.32-0.88, p = 0.015). This association was largely driven by the higher rate of early radical cystectomy among nonresponders., Conclusions: Despite bacillus Calmette-Guerin therapy and early radical cystectomy, patients with primary carcinoma in situ had a high rate of disease progression. Response to bacillus Calmette-Guerin was significantly associated with a lower rate of disease progression or early radical cystectomy.

Purpose: We describe the rate of up staging and the cancer specific outcomes of patients with carcinoma in situ refractory to transurethral resection with intravesical therapy treated with radical cystectomy., Materials and Methods: The records of 3,207 patients treated with radical cystectomy for urothelial carcinoma of the bladder at 8 centers in the United States, Canada and Europe were reviewed., Results: Of the 3,207 patients who underwent radical cystectomy 243 (7.6%) had clinical carcinoma in situ only disease before radical cystectomy. At radical cystectomy 117 patients (48.1%) had carcinoma in situ only, 20 (8.2%) had pT0 urothelial carcinoma of the bladder, 19 (7.8%) had pTa urothelial carcinoma of the bladder and 36% had disease up staged (32 [13.2%] pT1, 29 [11.9%] pT2, 12 [4.9%] pT3 and 14 [5.8%] pT4). A total of 22 patients (9.1%) had lymphovascular invasion in the radical cystectomy specimen and 14 (5.8%) had metastasis to regional lymph nodes. Overall 5-year recurrence-free and cancer specific survival estimates were 74% (95% CI 68-79) and 85% (95% CI 80-89), respectively. On multivariable analysis adjusting for the effects of standard predictors, lymph node metastasis and lymphovascular invasion were associated with an increased risk of disease recurrence (p = 0.017 and p = 0.043, respectively) and cancer specific mortality (p = 0.019 and p = 0.001, respectively). Female gender was an independent risk factor for cancer specific mortality (p = 0.029) but not for disease recurrence (p = 0.173)., Conclusions: Approximately a fourth of patients treated with radical cystectomy for clinical carcinoma in situ only had muscle invasive disease and 5.8% had metastasis to regional lymph nodes. Identification of those patients with a potentially aggressive natural history of carcinoma in situ is of the utmost importance as they are likely to benefit from early radical cystectomy., (2010 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Major controversies still exist with regard to the indication, type and regimen of intravesical therapy for non-muscle-invasive bladder cancer. Other areas of controversy are the criteria for response/failure of treatment and for decisions regarding secondary intravesical therapy versus radical cystectomy. In this article, we analyze the different intravesical therapeutic strategies and compare their safety and efficacy. Well-designed clinical trials have found that the addition of bacillus Calmette-Guerin (BCG) to transurethral resection (TUR) decreases the risk for both disease recurrence and progression. These encouraging results are sustained even in patients with recurrent or aggressive disease, including patients whose prior intravesical chemotherapy has failed. Most investigators believe that the efficacy of BCG therapy can be maximized with maintenance therapy. Mitomycin C (MMC), the most commonly used intravesical chemotherapy to date, decreases the risk of disease recurrence but not disease progression when used after TUR compared with TUR alone. The oncologic efficacy of intravesical MMC can be optimized by increasing its concentration in addition to alkalinizing and reducing urine production. For patients at high risk of disease progression, BCG with maintenance therapy should be the preferred primary intravesical therapeutic strategy. However, MMC can be considered as a viable alternative for patients with papillary tumors (no carcinoma in situ) that are at low or intermediate risk of disease progression. Combination intravesical therapy may be more successful than single-agent strategies. Intravesical therapy failures indicate the need to include radical cystectomy as an option in the management decision.

Purpose: We tested whether the altered immunohistochemical expression of angiogenesis related markers is associated with outcomes of patients with urothelial carcinoma of the bladder, and assessed the correlation of angiogenesis related markers with molecular markers commonly altered in urothelial bladder carcinoma., Materials and Methods: Vascular endothelial growth factor, basic fibroblast growth factor and thrombospondin 1 expression data were collected, as were microvessel density data. Immunohistochemical staining was performed on specimens from 204 patients treated with radical cystectomy for urothelial carcinoma of the bladder. We also stained serial sections of the specimens for cyclin E1, cyclin D1, p53, p21, p27, pRB, Ki-67, Bcl-2, caspase-3, survivin and cyclooxygenase-2. We measured time to disease recurrence and cancer specific mortality, as well as the association with clinical and pathological features and other molecular markers., Results: The altered expression of vascular endothelial growth factor (over expression), basic fibroblast growth factor (over expression) and thrombospondin 1 (decreased expression) was 86%, 79% and 63%, respectively. Median microvessel density was 20. All 4 markers were associated with established clinicopathological features of aggressive urothelial carcinoma of the bladder (such as stage, lymphovascular invasion and lymph node metastasis) and other molecular markers. On multivariable analyses that adjusted for standard pathological features basic fibroblast growth factor and thrombospondin 1 were independent predictors of disease recurrence (HR 3.6, p = 0.002 and HR 2.2, p = 0.001, respectively) and cancer specific mortality (HR 2.8, p = 0.02 and HR 2.3, p = 0.003, respectively). When all 4 markers were included in 1 model basic fibroblast growth factor and thrombospondin 1 retained their independent association with disease recurrence (HR 2.9, p = 0.014 and HR 1.8, p = 0.022, respectively) and only thrombospondin 1 was independently associated with cancer specific mortality (HR 1.9, p = 0.031)., Conclusions: Angiogenesis related molecular markers are commonly altered in urothelial carcinoma of the bladder, making them a target for therapy. Down-regulation of thrombospondin 1 and up-regulation of basic fibroblast growth factor are independent predictors of clinical outcomes of patients with urothelial carcinoma of the bladder., (2010 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Prognostic factors after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC) are inconclusive, because most data in the literature have been obtained from small series., Objective: To assess the association of tumour necrosis with cancer recurrence and survival in a large international series of patients treated with RNU., Design, Setting, and Participants: Data were collected from 1425 patients treated with RNU at 13 centres and combined into a relational database. Pathologic slides were re-reviewed by genitourinary pathologists according to strict criteria. Extensive tumour necrosis was scored as >10% of the tumour area., Intervention: Patients underwent either open or laparoscopic RNU. Lymph node dissection was performed in the presence of enlarged nodes., Measurements: Recurrence was defined as tumour relapse in the operative field, lymph node (LN) metastasis, and/or distant metastases. Bladder recurrences were not considered. Associations of extensive tumour necrosis with recurrence-free survival and cancer-specific survival were evaluated by univariate and multivariate analyses., Results and Limitations: Extensive tumour necrosis was observed in 364 patients (25.5%) and was associated with advanced tumour stage, high tumour grade, sessile architecture, lymphovascular invasion (LVI), concomitant carcinoma in situ, and LN metastasis (p<0.0001 each). Extensive tumour necrosis was independently associated with disease recurrence and survival (p=0.037 and p=0.046, respectively) after adjusting for the effects of pathologic stage, grade, LVI, and LN status. The addition of extensive tumour necrosis to a base model comprising standard pathologic predictors marginally improved its predictive accuracy for both cancer-specific recurrence (1.5%) and survival (1.4%)., Conclusions: Extensive tumour necrosis is an independent predictor of clinical outcomes in patients who undergo RNU for UTUC. Assessment of tumour necrosis may help to identify patients who could benefit from multimodal therapy after RNU in the future. Evaluation of extensive tumour necrosis should be part of standard pathologic reporting., (Copyright © 2009 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Purpose: The number of centers performing robotic assisted radical cystectomy has recently increased, spurring greater concerns about oncological outcomes. In this review we summarize the most comprehensive articles published on the oncological outcomes of laparoscopic assisted, robotic assisted and open radical cystectomy., Materials and Methods: A MEDLINE/PubMed literature search was conducted in March 2009 to review English language articles published from 1998 onward. Of 217 selected articles on the 3 techniques 19 studies were selected for this review., Results: The laparoscopic series reported recurrence-free survival rates in the range of 83% to 85% at 1 to 2 years and 60% to 77% at 2 to 3 years, while the robotic assisted studies reported recurrence-free survival rates of 86% to 91% at 1 to 2 years. Large open surgery studies showed 62% to 68% recurrence-free survival at 5 years and 50% to 60% at 10 years, with overall survival of 59% to 66% at 5 years and 37% to 43% at 10 years. Overall survival in the laparoscopic cohorts was 90% to 100% at 1 to 2 years and 50% to 87% at 2 to 3 years. Publications reporting robotic cases demonstrated a 90% to 96% overall survival in 1 to 2 years of followup., Conclusions: Despite the surge of centers adopting minimally invasive approaches for radical cystectomy, the long-term effectiveness of these techniques has not yet been proven. This review of recent and landmark articles on open and minimally invasive procedures emphasizes the need for prospective controlled studies and long-term followup data to determine the proper use of laparoscopic and robotic assisted techniques in bladder cancer surgery., (2010 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: We tested whether the combination of 4 established cell cycle regulators (p53, pRB, p21 and p27) could improve the ability to predict clinical outcomes in a large multi-institutional collaboration of patients with pT3-4N0 or pTany Npositive urothelial carcinoma of the bladder. We also assessed whether the combination of molecular markers is superior to any individual biomarker., Materials and Methods: The study comprised 692 patients with pT3-4N0 or pTany Npositive urothelial carcinoma of the bladder treated with radical cystectomy and bilateral lymphadenectomy (median followup 5.3 years). Scoring was performed using advanced cell imaging and color detection software. The base model incorporated patient age, gender, stage, grade, lymphovascular invasion, number of lymph nodes removed, number of positive lymph nodes, concomitant carcinoma in situ and adjuvant chemotherapy., Results: Individual molecular markers did not improve the predictive accuracy for disease recurrence and cancer specific mortality. Combination of all 4 molecular markers into number of altered molecular markers resulted in significantly higher predictive accuracy than any single biomarker (p <0.001). Moreover addition of number of altered molecular markers to the base model significantly improved the predictive accuracy for disease recurrence (3.9%, p <0.001) and cancer specific mortality (4.3%, p <0.001). Addition of number of altered molecular markers retained statistical significance for improving the prediction of clinical outcomes in the subgroup of patients with pT3N0 (280), pT4N0 (83) and pTany Npositive (329) disease (p <0.001)., Conclusions: While the status of individual molecular markers does not add sufficient value to outcome prediction in patients with advanced urothelial carcinoma of the bladder, combinations of molecular markers may improve molecular staging, prognostication and possibly prediction of response to therapy.

The management of non-muscle-invasive urothelial carcinoma of the bladder (UCB) is a challenge for physicians and patients alike. This is largely due to the heterogeneous natural history of this disease, in which tumors range from indolent to rapidly progressive and eventually fatal. Moreover, the high rate of recurrence and progression cause significant morbidity, expense, and detriment to quality of life. The advent of effective and safe intravesical therapies has improved the management of non-muscle-invasive UCB. Nevertheless, despite over 30 years of research and clinical experience, the mechanism, risks, benefits, and optimal regimens and treatment algorithms remain unclear. Although immunotherapy with bacillus Calmette-Guerin (BCG) has been the mainstay of intravesical treatment and represents a significant advance in the interaction of immunology and oncology, its clinical effectiveness is accompanied by a wide range of adverse events. Here, we review the literature on intravesical immunotherapy and chemotherapy with the aim of evaluating the clinical utility of the different treatments and providing recommendations. Many studies over the years have compared efficacy and toxicities of different agents and regimens, and certain conclusions are now well supported by high-level evidence. Future perspectives and promising advances in drug development are discussed and areas of improvement are identified in order to promote better cancer control and decrease the rate and severity of side-effects.

Cigarette smoking (CS) is the main risk factor for bladder cancer development. There are more than 100 carcinogens present in cigarette smoke. Among the potential mediators of CS-induced alterations is nuclear factor-kappa (NF-kappaB), which is responsible for the transcription of genes related to cell transformation, tumor promotion, angiogenesis, invasion and metastasis. Curcumin is a polyphenol compound derived from Curcuma longa that suppress cellular transformation, proliferation, invasion, angiogenesis, and metastasis by down regulating NF-kappaB and its regulated genes. The aim of our study was to assess the effects of curcumin in bladder urothelial carcinoma. We studied the effects of curcumin in vitro and in vivo using the orthotropic syngeneic bladder tumor animal model MB49. Curcumin promotes apoptosis of bladder tumor cells in vitro. In vivo tumors of animals treated with curcumin were significantly smaller as compared to controls. Using immunohistochemistry, we demonstrated a decrease in the expression of Cox-2 by 8% and Cyclin D1 by 13% in the animals treated with curcumin; both genes regulated by NF-kappaB and related to cell proliferation. In this study, we showed that curcumin acts in bladder urothelial cancer, possibly dowregulating NF-kappaB-related genes, and could be an option in the treatment of urothelial neoplasms. The results of our study suggest that further research is warranted to confirm our findings.

Background: Since successful treatment of superficial bladder cancer with BCG requires proper induction of Th1 immunity, we have developed a rBCG-S1PT strain that induced a stronger cellular immune response than BCG. This preclinical study was designed to compare the modulatory effects of BCG and rBCG-S1PT on bladder TNF-alpha and IL-10 expression and to evaluate antitumour activity., Methods: For Experiment I, the MB49 bladder cancer cell line was used in C57BL/6 mice. Chemical cauterization of the bladder was performed to promote intravesical tumor implantation. Mice were treated by intravesical instillation with BCG, rBCG-S1PT or PBS once a week for four weeks. After 35 days the bladders were removed and weighed. TNF- and IL-10 cytokine responses were measured by qPCR. Experiment II was performed in the same manner as Experiment I, except the animals were not challenged with MB49 tumor cells., Results: rBCG-S1PT immunotherapy resulted in bladder weight reduction, compared to the BCG and control group. There were increases in TNF-alpha in the BCG-treated group, as well as increases in TNF-alpha and IL-10 mRNA in the rBCG-S1PT group., Conclusion: These data indicate a significant reduction of bladder tumor volume for the rBCG group, compared to the BCG and PBS groups. This suggests that rBCG could be a useful substitute for wild-type BCG and that the potential modulation between TNF-alpha and IL-10 cytokine productions may have therapeutic value.

Purpose: We developed and characterized by histopathology and immunohistochemistry a syngeneic murine bladder tumor model derived from the MB49 tumor cell line., Materials and Methods: Bladder tumor implantation was achieved by intravesical instillation of 5 x 105 MB49 tumor cells in C57BL/6 mice. A chemical lesion of the bladder was performed in order to promote intravesical tumor implantation. The bladder wall lesion was accomplished by transurethral instillation of silver nitrate (AgNO3). After 15 days, the animals were sacrificed, examined macroscopically for intravesical tumor and bladder weight. Histology and immunohistochemistry were performed using cytokeratin 7 (CK7), carcinoembrionic antigen (Dako-CEA), p53 and c-erbB2 oncoprotein (Her2/neu)., Results: Twenty-nine out of 30 animals (96.7%) developed intravesical tumors in a 15-day period. Macroscopically, the mean bladder weight was 0.196g (0.069-0.538g), 10 to 15 times the normal bladder weight. The immunohistochemical analysis showed significant membrane expression of CEA and CK7: a similar finding for human urothelial cancer. We also characterized absence of expression of p53 and anti-Her2/neu in the murine model., Conclusions: High tumor take rates were achieved by using the chemical induction of the bladder tumor. Although electric cauterization is widely described in the literature for syngeneic orthotopic animal models, the technique described in this study represents an alternative for intravesical bladder tumor implantation. Moreover, the histopathology and immunohistochemical analysis of the murine bladder tumor model derived from the MB49 cell line showed a resemblance to human infiltrating urothelial carcinoma, allowing clinical inference from experimental immunotherapy testing.

Context: Primary adenocarcinomas of the bladder are uncommon and usually occur by contiguity with or hematogenic dissemination of other adenocarcinomas such as colorectal, prostate and gynecological tract carcinomas. Mucinous and signet-ring cell histological patterns are even rarer and it is often difficult to morphologically distinguish them from metastatic colorectal adenocarcinoma., Case Report: We present and discuss a rare case of primary mucinous adenocarcinoma of the bladder with signet-ring cells in a 57-year-old male patient. Other primary sites for the tumor had been excluded and, in the absence of digestive tract tumor and for confirmation that it was a primary bladder tumor, an immunohistochemistry study was performed.