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Context Transurethral resection of bladder tumour (TURBT) for bladder cancer (BC) is an underappreciated common urological procedure. TURBT outcomes are highly variable, and results are dependent on judgement and surgical skill. Objective To perform a narrative review and identify optimal best practice in TURBT including preparation, choice of equipment, procedural steps, surgical technique, and management of difficult scenarios and complications. Evidence acquisition Medline, Embase, and the Cochrane Central Register of Controlled Trials were searched. Important studies were identified and reviewed by an international panel of urologists representing major urological societies and guideline panels with a record of academic publication in this field. In areas where the group identified a lack of evidence or agreement, discussions took place until a consensus was reached. Evidence synthesis A total of 814 studies were identified and 43 were included. The majority were retrospective (level of evidence 3), with only two prospective randomised trials. Four broad themes were identified, which formed the basis for the review: (1) the role of TURBT within the overall management of BC, (2) TURBT techniques, (3) measurement of outcomes including quality control and checklists, and (4) postoperative management. Familiarity with all aspects of the procedure is necessary to minimise morbidity and improve oncological outcomes. Development of new instruments and techniques, and prospective audit of TURBT outcomes are important future goals. Conclusions TURBT is a common and challenging operation with known variable outcomes. To reduce these variations and optimise outcomes, best practice based on evidence and expert opinion is recommended. Patient summary Transurethral resection of bladder tumour (TURBT) is a common but deceptively difficult urological operation. Optimal outcomes depend on experience and surgical skill. An international group of experienced TURBT surgeons review critical aspects of the procedure and share best practice to stimulate further discussion.

Contains fulltext : 220546.pdf (Publisher’s version ) (Closed access) OBJECTIVE: To provide a contemporary update and recommendations for the diagnosis and management of low-grade non-muscle-invasive bladder cancer (BCa) based on current literature and expert consensus of the International Bladder Cancer Group. METHODS: We reviewed published trials, guidelines, meta-analyses and reviews (up to March 2019) and provide recommendations on baseline evaluations, treatment, endpoints, study design and surveillance protocols. RESULTS: Low-grade Ta BCa poses minimal risk to patients in terms of progression and disease-specific survival. Thus, to minimize patient morbidity, this entity should be managed appropriately. After initial diagnosis of low-grade Ta tumour, subsequent stable, low-grade-appearing recurrences can be managed conservatively with office cystoscopy and fulguration or even followed using an active surveillance protocol. Intravesical therapy other than single-dose peri-operative chemotherapy instillation should be used judiciously, and only after assigning appropriate risk points. Routine use of urinary cytology - other than at initial risk stratification, or for patients on active surveillance without therapy - is not recommended; and surveillance cystoscopy may be discontinued after 5 years. Clinical studies in this group of patients should focus on recurrence rates, and time to recurrence, rather than progression events. CONCLUSIONS: The International Bladder Cancer Group has developed formal recommendations regarding the diagnosis, treatment and surveillance of low-grade non-muscle-invasive BCa to minimize morbidity and encourage uniformity among studies in this disease.

There is a paucity of management recommendations for patients with aggressive Diffuse large B cell lymphoma (DLBCL) of the bladder. A 57-year-old male patient presented with lower urinary tract symptoms underwent flexible cystoscopy and then bladder tumor biopsy. Through immediate staging CT scan, tumor and bone biopsies he was diagnosed with a 16 cm Stage IVa high-grade DLBCL. He was treated with DA EPOCH with only a partial response and was transitioned to R-ICE. For rarer presentations of bladder cancer during diagnostic cystoscopy there should be no delay in tumor imaging and involving medical oncology in early treatment decision making.

To update current recommendations on prevention, screening, diagnosis, and evaluation of bladder cancer (BC) based on a thorough assessment of the most recent literature on these topics. A non-systematic review was performed, including articles until June 2017. A variety of original articles, reviews, and editorials were selected according to their epidemiologic, demographic, and clinical relevance. Assessment of the level of evidence and grade of recommendations was performed according to the International Consultation on Urological Diseases grading system. BC is the ninth most common cancer worldwide with 430,000 new cases in 2012. Currently, approximately 165,000 people die from the disease annually. Absolute incidence and prevalence of BC are expected to rise significantly during the next decades because of population ageing. Tobacco smoking is still the main risk factor, accounting for about 50% of cases. Smoking cessation is, therefore, the most relevant recommendation in terms of prevention, as the risk of developing BC drops almost 40% within 5 years of cessation. BC screening is not recommended for the general population. BC diagnosis remains mainly based on cystoscopy, but development of new endoscopic and imaging technologies may rapidly change the diagnosis algorithm. The same applies for local, regional, and distant staging modalities. A thorough understanding of epidemiology, risk factors, early detection strategies, diagnosis, and evaluation is essential for correct, evidence-based management of BC patients. Recent developments in endoscopic techniques and imaging raise the hope for providing better risk-adopted approaches and thereby improving clinical outcomes.

The 5-year survival rate of patients with metastatic renal cell carcinoma (mRCC) is

Background: Aberrantly expressed miRNAs promote renal cell carcinoma (RCC) growth and metastasis and are potentially useful biomarkers for metastatic disease. However, a consensus clinically significant miRNA signature has not been identified. To identify an miRNA signature for predicting clinical outcome in RCC patients, we used a four-pronged interconnected approach. Methods: Differentially expressed miRNAs were identified and analyzed in 113 specimens (normal kidney: 59; tumor: 54). miRNA profiling was performed in matched normal and tumor specimens from 8 patients and extended to 32 specimens. Seven aberrantly expressed miRNAs were analyzed by qPCR, and their levels were correlated with RCC subtypes and clinical outcome. miRNA signature was confirmed in The Cancer Genome Atlas RCC dataset (n = 241). Results: Discovery phase identified miR-21, miR-142-3p, miR-142-5p, miR-150, and miR-155 as significantly upregulated (2–4-fold) and miR-192 and miR-194 as downregulated (3–60-fold) in RCC; miR-155 distinguished small tumors ( Conclusions: The interconnected discovery–validation approach identified a three-miRNA signature as a potential predictor of disease outcome in RCC patients. Impact: With 10% survival at 5 years, metastatic disease presents poor prognosis for RCC patients. The three-miRNA signature discovered and validated may potentially at an early stage detect and predict metastasis, to allow early intervention for improving patient prognosis. Cancer Epidemiol Biomarkers Prev; 27(4); 464–72. ©2018 AACR.

Background: Molecular markers of clinical outcome may aid in designing targeted treatments for bladder cancer. However, only a few bladder cancer biomarkers have been examined as therapeutic targets. Methods: Data from The Cancer Genome Atlas (TCGA) and bladder specimens were evaluated to determine the biomarker potential of the hyaluronic acid (HA) family of molecules – HA synthases, HA receptors and hyaluronidase. The therapeutic efficacy of 4-methylumbelliferone (4MU), a HA synthesis inhibitor, was evaluated in vitro and in xenograft models. Results: In clinical specimens and TCGA data sets, HA synthases and hyaluronidase-1 levels significantly predicted metastasis and poor survival. 4-Methylumbelliferone inhibited proliferation and motility/invasion and induced apoptosis in bladder cancer cells. Oral administration of 4MU both prevented and inhibited tumour growth, without dose-related toxicity. Effects of 4MU were mediated through the inhibition of CD44/RHAMM and phosphatidylinositol 3-kinase/AKT axis, and of epithelial–mesenchymal transition determinants. These were attenuated by HA, suggesting that 4MU targets oncogenic HA signalling. In tumour specimens and the TCGA data set, HA family expression correlated positively with β-catenin, Twist and Snail expression, but negatively with E-cadherin expression. Conclusions: This study demonstrates that the HA family can be exploited for developing a biomarker-driven, targeted treatment for bladder cancer, and 4MU, a non-toxic oral HA synthesis inhibitor, is one such candidate.

The term "definitive therapy" for localized prostate cancer is a misnomer. Patients may be confused as to why "definitive therapy" sometimes requires further treatment after failure. This term should be replaced with "primary therapy".

Item does not contain fulltext Intravesical immunotherapy with live attenuated BCG remains the standard of care for patients with high-risk and intermediate-risk non-muscle-invasive bladder cancer (NMIBC). Most patients initially respond, but recurrence is frequent and progression to invasive cancer is a concern. No established and effective intravesical therapies are available for patients whose tumours recur after BCG, representing a clinically important unmet need. Development and discovery of treatment options for BCG-unresponsive NMIBC is a high priority in order to decrease the morbidity, burden of health-care expenditures, and mortality related to bladder cancer. This Review of treatment options after BCG failure focuses on principles of optimal management emerging therapies, thus enabling a synthesis of recommendations for management for such patients.

Contains fulltext : 220581.pdf (Publisher’s version ) (Closed access) Transurethral resection of bladder tumour is the initial, most critical step in the management of bladder cancer; as such, this is a call to arms for the urological community to it the due diligence it deserves regarding technology and training.

Management of low-grade bladder cancer should focus on minimizing morbidity and costs given the excellent oncologic outcomes.

Studies indicate that molecular subtypes in muscle invasive bladder cancer predict the clinical outcome. We evaluated whether subtyping by a simplified method and established classifications could predict the clinical outcome.We subtyped institutional cohort 1 of 52 patients, including 39 with muscle invasive bladder cancer, an Oncomine™ data set of 151 with muscle invasive bladder cancer and TCGA (The Cancer Genome Atlas) data set of 402 with muscle invasive bladder cancer. Subtyping was done using simplified panels (MCG-1 and MCG-Ext) which included only transcripts common in published studies and were analyzed for predicting metastasis, and cancer specific, overall and recurrence-free survival. TCGA data set was further analyzed using the Lund taxonomy, the Bladder Cancer Molecular Taxonomy Group Consensus and TCGA 2017 mRNA subtype classifications.Muscle invasive bladder cancer specimens from cohort 1 and the Oncomine data set showed intratumor heterogeneity for transcript and protein expression. MCG-1 subtypes did not predict the outcome on univariate or Kaplan-Meier analysis. On multivariate analysis N stage (p ≤0.007), T stage (p ≤0.04), M stage (p=0.007) and/or patient age (p=0.01) predicted metastasis, cancer specific and overall survival, and/or the cisplatin based adjuvant chemotherapy response. In TCGA data set publications showed that subtypes risk stratified patients for overall survival. Consistently the MCG-1 and MCG-Ext subtypes were associated with overall but not recurrence-free survival on univariate and Kaplan-Meier analyses. TCGA data set included 21 low grade specimens of the total of 402 and subtypes associated with tumor grade (p=0.005). However, less than 1% of muscle invasive bladder cancer cases are low grade. In only high grade specimens the MCG-1 and MCG-Ext subtypes could not predict overall survival. On univariate analysis subtypes according to the Bladder Cancer Molecular Taxonomy Group Consensus, TCGA 2017 and the Lund taxonomy were associated with tumor grade (p0.0001) and overall survival (p=0.01 to0.0001). Regardless of classification, subtypes had about 50% to 60% sensitivity and specificity to predict overall and recurrence-free survival. On multivariate analyses N stage and lymphovascular invasion consistently predicted recurrence-free and overall survival (p=0.039 and 0.003, respectively).Molecular subtypes reflect bladder tumor heterogeneity and are associated with tumor grade. In multiple cohorts and subtyping classifications the clinical parameters outperformed subtypes for predicting the outcome.

Purpose To provide recommendations on appropriate clinical trial designs in non–muscle-invasive bladder cancer (NMIBC) based on current literature and expert consensus of the International Bladder Cancer Group. Methods We reviewed published trials, guidelines, meta-analyses, and reviews and provided recommendations on eligibility criteria, baseline evaluations, end points, study designs, comparators, clinically meaningful magnitude of effect, and sample size. Results NMIBC trials must be designed to provide the most clinically relevant data for the specific risk category of interest (low, intermediate, or high). Specific eligibility criteria and baseline evaluations depend on the risk category being studied. For the population of patients for whom bacillus Calmette-Guérin (BCG) has failed, the type of failure (BCG unresponsive, refractory, relapsing, or intolerant) should be clearly defined to make comparisons across trials feasible. Single-arm designs may be relevant for the BCG-unresponsive population. Here, a clinically meaningful initial complete response rate (for carcinoma in situ) or recurrence-free rate (for papillary tumors) of at least 50% at 6 months, 30% at 12 months, and 25% at 18 months is recommended. For other risk levels, randomized superiority trial designs are recommended; noninferiority trials are to be used sparingly given the large sample size required. Placebo control is considered unethical for all intermediate- and high-risk strata; therefore, control arms should comprise the current guideline-recommended standard of care for the respective risk level. In general, trials should use time to recurrence or recurrence-free survival as the primary end point and time to progression, toxicity, disease-specific survival, and overall survival as potential secondary end points. Realistic efficacy thresholds should be set to ensure that novel therapies receive due review by regulatory bodies. Conclusion The International Bladder Cancer Group has developed formal recommendations regarding definitions, end points, and clinical trial designs for NMIBC to encourage uniformity among studies in this disease.

Contains fulltext : 195581.pdf (Publisher’s version ) (Open Access) Background: Guidelines recommend a single postoperative instillation of intravesical chemotherapy within 24 hours of transurethral resection of bladder tumors (TURBT) in patients with low- and intermediate-risk non-muscle invasive bladder cancer (NMIBC) to reduce recurrence risk. Objective: To evaluate the 2-year recurrence rate (2-YRR) of bladder cancer in randomized patients with Ta, G1-G2 histology who receive TURBT plus apaziquone versus TURBT plus placebo. Methods: Two nearly identical Phase 3, multinational, randomized, double-blind, placebo-controlled trials were conducted in patients with histologically confirmed Ta, G1-G2 NMIBC (Target Population) to evaluate the efficacy/safety of a single instillation of apaziquone post-TURBT. A single intravesical instillation of apaziquone (4 mg/40 mL) or placebo was administered within 6 hours post-TURBT. The primary and secondary efficacy endpoints were 2-YRR and time to recurrence (TTR) respectively. Results: Overall, 1614 patients were enrolled, including 1146 patients in the Target Population. Individually, the two studies did not meet statistical significance for 2-YRR (38.0% vs 44.6% ; 39.7% vs. 46.3%). Because apaziquone is rapidly metabolized in blood, a post hoc subgroup analysis was performed by time window of drug instillation post-TURBT. Patients who had drug instilled in the time window 60+/-30 minutes post-TURBT demonstrated 20.3% and 20.8% reduction in 2-YRR and 56% (HR = 0.44) and 45% (HR = 0.55) reduction in hazards for TTR in two studies respectively. Apaziquone was well tolerated with minimal toxicity. Conclusions: Two identical Phase 3 studies supported the safety of apaziquone (4 mg/40 mL) administered as a single intravesical instillation post-TURBT and identified efficacy when instilled within 60+/-30-minutes time interval which requires further study.

Introduction Active surveillance with delayed intervention aims to minimize the discomfort, potential complications and costs associated with immediate treatment of recurrent low grade Ta tumors of the bladder. We reviewed the data supporting this management strategy for low risk bladder cancer. Methods A PubMed® query was performed to identify relevant literature on the topic of active surveillance for low risk bladder cancer. English language publications were reviewed and select data presented. Results Available data suggest that only 5% to 10% of patients diagnosed with a low grade appearing papillary bladder tumor will have progression in stage or grade. Coupled with the discomfort and potential for complications associated with transurethral resection, this supports the role of active surveillance for patients with small, recurrent, low risk bladder cancer. In addition, this management strategy stands to benefit the health care system by reducing the costs associated with caring for patients with bladder cancer. Conclusions Active surveillance with delayed intervention represents a safe and cost-effective strategy for patients with recurrent low risk bladder cancer.

SDF-1 is a ligand of the chemokine receptors CXCR4 and 7. The 6 known SDF-1 isoforms are generated by alternative mRNA splicing. While SDF-1 expression has been detected in various malignancies, only few groups have reported differential expression of SDF-1 isoforms and its clinical significance. We evaluated the expression of 3 SDF-1 isoforms (α, β and γ) in bladder cancer.Using quantitative polymerase chain reaction we measured SDF-1α, β and γ mRNA levels in 25 normal and 44 bladder cancer tissues, and in 210 urine specimens (28 normal, 74 benign, 57 bladder cancer, 35 bladder cancer history, 8 other cancer history and 8 other cancer) from consecutive patients. Levels were correlated with clinical outcome.Of the SDF-1 isoforms only SDF-1β mRNA was significantly over expressed 2.5-fold to sixfold in bladder cancer compared to normal bladder tissues. SDF-1α was expressed in bladder tissues but SDF-1γ was undetectable. On multivariate analysis SDF-1β was an independent predictor of metastasis and disease specific mortality (p=0.017 and 0.043, respectively). In exfoliated urothelial cells only SDF-1β mRNA levels were differentially expressed with 91.2% sensitivity and 73.8% specificity for detecting bladder cancer. In patients with a bladder cancer history increased SDF-1β levels indicated a 4.3-fold increased risk of recurrence within 6 months (p=0.0001).SDF-1 isoforms are differentially expressed in bladder tissues and exfoliated urothelial cells. SDF-1β mRNA levels in bladder cancer tissues predict a poor prognosis. Furthermore, SDF-1β mRNA levels in exfoliated cells detect bladder cancer with high sensitivity and they are a potential predictor of future recurrence.

Item does not contain fulltext PURPOSE: Despite being one of the most important clinical outcomes in nonmuscle invasive bladder cancer, there is currently no standard definition of disease progression. Major clinical trials and meta-analyses have used varying definitions or have failed to define this end point altogether. A standard definition of nonmuscle invasive bladder cancer progression as determined by reproducible and reliable procedures is needed. We examine current definitions of nonmuscle invasive bladder cancer progression, and propose a new definition that will be more clinically useful in determining patient prognosis and comparing treatment options. MATERIALS AND METHODS: The IBCG (International Bladder Cancer Group) analyzed published clinical trials and meta-analyses that examined nonmuscle invasive bladder cancer progression as of December 2012. The limitations of the definitions of progression used in these trials were considered, as were additional parameters associated with the advancement of nonmuscle invasive bladder cancer. RESULTS: The most commonly used definition of nonmuscle invasive bladder cancer progression is an increase in stage from nonmuscle invasive to muscle invasive disease. Although this definition is clinically important, it fails to include other important parameters of advancing disease such as progression to lamina propria invasion and increase in grade. CONCLUSIONS: The IBCG proposes the definition of nonmuscle invasive bladder cancer progression as an increase in T stage from CIS or Ta to T1 (lamina propria invasion), development of T2 or greater or lymph node (N+) disease or distant metastasis (M1), or an increase in grade from low to high. Investigators should consider the use of this new definition to help standardize protocols and improve the reporting of progression.

BACKGROUND Many patients with low-risk prostate cancer (PC) who are diagnosed with Gleason score 6 at biopsy are ultimately found to harbor higher grade PC (Gleason ≥ 7) at radical prostatectomy. This finding increases risk of recurrence and cancer-specific mortality. Validated clinical tools that are available preoperatively are needed to improve the ability to recognize likelihood of upgrading in patients with low-risk PC. METHODS More than 30 clinicopathologic parameters were assessed in consecutive patients with Gleason 6 PC upon biopsy who underwent radical prostatectomy. A nomogram for predicting upgrading (Gleason ≥ 7) on final pathology was generated using multivariable logistic regression in a development cohort of 431 patients. External validation was performed in 2 separate cohorts consisting of 1151 patients and 392 patients. Nomogram performance was assessed using receiver operating characteristic curves, calibration, and decision analysis. RESULTS On multivariable analysis, variables predicting upgrading were prostate-specific antigen density using ultrasound (odds ratio [OR] = 229, P = .003), obesity (OR = 1.90, P = .05), number of positive cores (OR = 1.23, P = .01), and maximum core involvement (OR = 0.02, P = .01). On internal validation, the bootstrap-corrected predictive accuracy was 0.753. External validation revealed a predictive accuracy of 0.677 and 0.672. The nomogram demonstrated excellent calibration in all 3 cohorts and decision curves demonstrated high net benefit across a wide range of threshold probabilities. The nomogram demonstrated areas under the curve of 0.597 to 0.672 for predicting upgrading in subsets of men with very low-risk PC who meet active surveillance criteria (all P

We analyzed the prognostic implications of positive margins and extraprostatic extension missed by different methods of partially sampling prostatectomy specimens.The study group consisted of 1,499 patients treated with radical prostatectomy. All specimens were processed uniformly and submitted entirely. For each patient with a positive margin or extraprostatic extension we determined whether these pathological characteristics would have been diagnosed had the specimen been examined by 3 partial sampling techniques. The Harrell concordance index was used to quantify the predictive performance of the Cox models based on the potential findings of the different sampling methods.Partial sampling methods 1 and 2, which included the examination of alternate slides, missed 13% to 21% of positive margins and 27% to 46% of extraprostatic extensions. The effect on biochemical recurrence-free survival of these undetected pathological features was similar to that of positive margins and extraprostatic extension that would have been diagnosed by corresponding techniques. Method 3, which sampled the entire posterior region, the mid anterior prostate and the rest of the ipsilateral anterior gland (if sizeable tumor was seen), detected 95% of positive margins and 94% of extraprostatic extensions. The extraprostatic extension missed by this method was not associated with a significant increase in the risk of biochemical recurrence. The Harrell concordance index of the multivariate models was 0.806, 0.797, 0.795 and 0.804 based on the results of complete sampling, and methods 1, 2 and 3, respectively.Examining alternate sections of prostatectomy specimen results in missing clinically important positive margins and extraprostatic extension. It decreases our ability to predict biochemical recurrence-free survival.

Objective To develop a clinical tool that integrates different risk factors and provides individual predictions of the risk of biopsy progression in patients with prostate cancer managed by active surveillance. Materials and Methods Our analysis included 205 patients on active surveillance, each of whom had had at least two surveillance biopsies. We used the Cox proportional hazard regression model to analyse the association between different risk factors and progression-free survival over successive biopsies. This multivariate model was then used to develop a nomogram. Discrimination and calibration of the nomogram were internally validated using 200 bootstrap resamplings. Results The median follow-up of patients free of progression was 4.6 years. A total of 58 (28%) patients experienced progression. Factors significantly associated with progression were: overall number of positive cores in the diagnostic and first surveillance biopsies, race and prostate-specific antigen density. The bootstrapping concordance index of the nomogram including these variables was 81%. The nomogram tended to underestimate the probability of progression but it identified fairly accurately the distinct groups of patients at low, intermediate and high risk of progression. Conclusions In the development cohort, the nomogram was able to separate patients with respect to their risk of biopsy progression. Since accurate risk stratification is essential to optimize patient care, this tool, if external validation confirms its performance, may prove useful for both the counselling and management of patients with low-volume, Gleason 6 prostate cancer.

Currently there is no global agreement as to how ex- tensively a radical prostatectomy specimen should be sectioned and histologically examined. We analyzed the ability of different methods of partial sampling in detecting positive margin (PM) and extraprostatic extension (EPE)—2 pathologic features of prostate cancer that are most easily missed by partial sampling of the prostate. Radical prostatectomy specimens from 617 pa- tients treated with open radical prostatectomy between 1992 and 2011 were analyzed. Examination of the entirely submitted prostate detected only PM in 370 (60%), only EPE in 100 (16%), and both in 147 (24%) specimens. We determined whether these pathologic features would have been diagnosed had the examination of the specimen been limited only to al- ternate sections (method 1), alternate sections representing the posterior aspect of the gland in addition to one of the mid- anterior aspects (method 2), and every section representing the posterior aspect of the gland in addition to one of the mid- anterior aspects, supplemented by the remaining ipsilateral an- terior sections if a sizeable tumor is seen (method 3). Methods 1 and 2 missed 13% and 21% of PMs and 28% and 47% of EPEs, respectively. Method 3 demonstrated better results missing only 5% of PMs and 7% of EPEs. Partial sampling techniques missed slightly more PMs and EPEs in patients with low-risk to intermediate-risk prostate cancer, although even in high-risk cases none of the methods detected all of the studied aggressive pathologic features.

Context The Second International Consultation on Bladder Cancer recommendations on urothelial carcinoma (UC) of the prostate were presented at the 2011 European Association of Urology Congress in Vienna, Austria, on March 18, 2011. Objective Our aim is to summarize the Second International Consultation on Bladder Cancer recommendations on UC of the prostate to help clinicians assess the current evidence-based management. Evidence acquisition The committee performed a thorough review of new data and updated previous recommendations. Levels of evidence and grades of recommendation were assigned based on a systematic review of the literature that included a search of online databases and review articles. Evidence synthesis Once a non–muscle-invasive high-grade tumor or carcinoma in situ (CIS) of the bladder has been diagnosed, careful follow-up of the prostatic urethra is necessary. Noninvasive UC including CIS of the prostate should be treated with intravesical bacillus Calmette-Guerin (BCG) following endoscopic resection. A transurethral resection of the prostate may improve contact of BCG with the prostatic urethra, and it appears that response rates to BCG are increased (level of evidence: 3). Transurethral biopsy of the prostatic urethra is effective in identifying prostatic involvement but may not accurately reveal the extent of involvement, particularly with stromal invasion. Stromal invasion by UC of the prostate carries a poor prognosis. Radical cystoprostatectomy is the treatment of choice for locoregional control in patients with prostatic stromal invasion. Conclusions These recommendations contain updated information on the diagnosis and treatment of UC of the prostate. However, prospective trials are needed to further elucidate the best management of these patients.

Context New guidelines of the International Consultation on Urological Diseases for the treatment of muscle-invasive bladder cancer (MIBC) have recently been published. Objective To provide a comprehensive overview of the current role of radical cystectomy (RC) in MIBC. Evidence acquisition A detailed Medline analysis was performed for original articles addressing the role of RC with regard to indication, timing, surgical extent, perioperative morbidity, oncologic outcome, and follow-up. The analysis also included radiation-based bladder-preserving strategies. Evidence synthesis The major findings are presented in an evidence-based fashion and are based on large retrospective unicenter and multicenter series with some prospective data. Conclusions Open RC is the standard treatment for locoregional control of MIBC. Delay of RC is associated with reduced cancer-specific survival. In males, standard RC includes the removal of the bladder, prostate, seminal vesicles, and distal ureters; in females, RC includes an anterior pelvic exenteration including the bladder, entire urethra and adjacent vagina, uterus, and distal ureters. A procedure sparing the urethra and the urethra-supplying autonomous nerves can be performed in case of a planned orthotopic neobladder. Further technical variations (ie, seminal-sparing or vaginal-sparing techniques) aimed at improving functional outcomes must be weighed against the risk of a positive margin. Laparoscopic surgery is promising, but long-term data are required prior to accepting it as an option equivalent to the open procedure. Lymphadenectomy should remove all lymphatic tissue around the common iliac, external iliac, internal iliac, and obturator region bilaterally. Complications after RC should be reported according to the modified Clavien grading system. In selected patients with MIBC, bladder-preserving therapy with cystectomy reserved for tumor recurrence represents a safe and effective alternative to immediate RC.

Item does not contain fulltext CONTEXT: Our aim was to present a summary of the Second International Consultation on Bladder Cancer recommendations on the diagnosis and treatment options for non-muscle-invasive urothelial cancer of the bladder (NMIBC) using an evidence-based approach. OBJECTIVE: To critically review the recent data on the management of NMIBC to arrive at a general consensus. EVIDENCE ACQUISITION: A detailed Medline analysis was performed for original articles addressing the treatment of NMIBC with regard to diagnosis, surgery, intravesical chemotherapy, and follow-up. Proceedings from the last 5 yr of major conferences were also searched. EVIDENCE SYNTHESIS: The major findings are presented in an evidence-based fashion. We analyzed large retrospective and prospective studies. CONCLUSIONS: Urothelial cancer of the bladder staged Ta, T1, and carcinoma in situ (CIS), also indicated as NMIBC, poses greatly varying but uniformly demanding challenges to urologic care. On the one hand, the high recurrence rate and low progression rate with Ta low-grade demand risk-adapted treatment and surveillance to provide thorough care while minimizing treatment-related burden. On the other hand, the propensity of Ta high-grade, T1, and CIS to progress demands intense care and timely consideration of radical cystectomy.

Context To present a summary of the 2nd International Consultation on Bladder Cancer recommendations on the pathology of bladder cancer using an evidence-based strategy. Objective To standardize descriptions of the diagnosis and reporting of urothelial carcinoma of the bladder and help optimize uniformity between individual pathology practices and institutions. Evidence acquisition A detailed Medline analysis was performed for original articles addressing bladder cancer with regard to pathology. Proceedings from the last 5 yr of major conferences were also searched. Evidence synthesis The major findings are presented in an evidence-based fashion. Large retrospective and prospective data were analyzed. Conclusions Providing the best management for patients with bladder neoplasia relies on close cooperation and teamwork among urologists, oncologists, radiologists, and pathologists.

Context We present a summary of the Second International Consultation on Bladder Cancer recommendations on chemotherapy for the treatment of bladder cancer using an evidence-based strategy. Objective To review the data regarding chemotherapy in patients with clinically localized and metastatic bladder cancer with a focus on its use for patients in the neoadjuvant and adjuvant settings. Evidence acquisition Medline databases were searched for original articles published prior to April 1, 2012, using the following search terms: bladder cancer, urothelial cancer, metastatic, advanced, neoadjuvant , and adjuvant therapy. Proceedings of major conferences from the last 5 yr also were searched. Novel and promising drugs currently in clinical trials were included. Evidence synthesis The major findings are addressed in an evidence-based manner. Prospective trials and important cohort data were analyzed. Conclusions Cisplatin-based combination chemotherapy for advanced and metastatic bladder cancer is an established standard, improving overall survival. In the advanced setting, cisplatin-ineligible patients may benefit from gemcitabine and carboplatin. Meta-analyses undertaken for neoadjuvant cisplatin-based combination chemotherapy show a 5% benefit in overall survival. Pathologic complete remission may be an intermediate surrogate for survival, but requires further validation. Use of neoadjuvant chemotherapy is low, and is attributable to patient and physician choice because of limited benefit, advanced age, and comorbidities including renal and/or cardiac dysfunction. Sufficient data to support adjuvant chemotherapy are lacking.

Objective To evaluate the effect of prostate cancer zonal origin on the biochemical outcome after radical prostatectomy, to analyze clinicopathological features of tumors arising in different zones and to test the ability of the nomogram to predict the probability of transition zone cancer at radical prostatectomy. Methods Our cohort consisted of 1441 patients who underwent radical prostatectomy who did not receive neoadjuvant treatment. Clinicopathological characteristics and biochemical outcomes were compared between the groups of men with different zonal location of prostate cancer. Performance of the nomogram in predicting cancer location was evaluated with respect to discrimination and calibration. Results The rates of positive margin were similar in men with transition zone and mixed tumors and were significantly higher than those with peripheral zone tumors. Most of the positive margins in patients with transition zone and mixed cancers were located at the apico-anterior part of the gland. On multivariate analysis, transition zone cancer location was associated with better biochemical recurrence-free survival ( P = .043). The Harrel c-index of the models that did and did not include zonal origin of cancer was 0.810 and 0.807, respectively. Performance of the nomogram was poor. Conclusion The association between transition zone tumor origin and the risk of biochemical recurrence does not add important predictive value to the standard prognostic factors. Although information about the risk of prostate cancer involvement of the transition zone may be important for surgical planning, our ability to predict this risk preoperatively is limited.

A 40-year-old woman presents to the emergency department after a motor vehicle accident, and a CT scan revealed no injuries but incidentally notes three non-obstructing stones in the left kidney of 3, 4, and 5 mm in size. She is completely asymptomatic and has no history of urolithiasis.

The patient is an 80-year-old man who presented with gross hematuria. His past medical history indicates he was a cigarette smoker with 50 pack/years. He was successfully treated for carcinoma of the lung 7 years ago. He received chemotherapy, radiation, and surgery. He has mild COPD but has a good performance status. His laboratory studies do not indicate any abnormalities in terms of renal function. He does not have any significant cardiac disease. He has a medium build. He had prostate cancer and underwent a successful radical prostatectomy 10 years ago. His PSA is undetectable. He has some urinary incontinence and wears two pads/day. He underwent the appropriate investigations for gross hematuria. A CT scan of the abdomen and pelvis was normal with the exception of a 4-cm posterior mass in the bladder. There was no hydronephrosis and no enlarged lymph nodes. He underwent a transurethral resection of a solitary bladder tumor performed by another urologist. The tumor was described as large and sessile. It was located on the posterior wall and was approximately 4 cm. The bimanual examination did not reveal a mass. The pathology report stated that the tumor was a high-grade urothelial carcinoma with invasion into the muscularis propria. There was no lymphovascular invasion. I performed a reTURBT, and at that procedure, I did not identify any obvious tumor but the prior resection site was evident. I resected the prior tumor site quite extensively both in depth and width. The pathology revealed only focal carcinoma in situ. There was ample muscle in the specimen and there was some fat as well. As stated, they were free of any cancer. The patient is receptive to any treatment approach.

The authors present a four-year experience with prostate capsule sparing (PCS) laparoscopic radical cystectomy (RC) [1]. First, these authors should be commended for their execution of a technically challenging procedure. Although this is a small series, the perioperative outcomes (operative time, blood loss, length of stay (LOS)) are similar to published data for the robotic-assisted procedure [2]. Of note, this paper once again shows that hospital LOS is not shortened with a minimally invasive approach, questioning the benefit to patients (the addition of PSC does not contribute to the perioperative convalescence). The authors present impressive potency (90%) and continence (90% day, 85% night) results, showcasing the quality of life (QOL) benefits of PCS. These numbers are consistent with other centers of excellence [3]. This leaves the oncologic outcomes as the controversial aspect of this procedure. There are two cancers to be considered: urothelial carcinoma of the prostate (UCP) and prostate adenocarcinoma (PC). As the authors point out, local recurrence rates of UCP are low with this technique (none in the present report). Similarly, Mertens et al. found UCP recurrence of

Prostate cancer treatment presents multiple challenges that can negatively affect health-related quality of life (HrQoL), and which may be further compromised by maladaptive personality styles and psychological adjustment difficulties. This study examined the utility of a comprehensive psychosocial screening tool to identify psychosocial traits that prospectively predict HrQoL status among men treated for localized prostate cancer. The Millon Behavioral Medicine Diagnostic (MBMD) was administered to 66 men (mean age 68 years, 59% Caucasian) treated by either radical prostatectomy or radiotherapy along with standard measures of general and prostate cancer-specific quality of life assessed at a 12-month follow-up. Higher scores on both summary MBMD Management Guides (Adjustment Difficulties and Psych Referral) and higher scores on personality styles characterized by avoidance, dependency, depression, passive aggressiveness and self-denigration predicted lower HrQoL (β range = −.21 to −.50). Additionally, higher scores on the MBMD Depression, Tension-Anxiety and Future Pessimism scales predicted lower HrQoL. Finally, higher scores on the MBMD Intervention Fragility and Utilization Excess scale, also consistently predicted poorer mental and physical health functioning over time. These results point to the utility of the MBMD to help screen for potential impairments in mental and physical health functioning in men undergoing treatment for prostate cancer.

What's known on the subject? and What does the study add? Active surveillance is an established management option for patients with favourable-risk prostate cancer. However, about 25–30% of active surveillance patients demonstrate biopsy progression within the first 3–5 years of follow-up. Although several factors, such as the results of the diagnostic and surveillance biopsies, are known to be associated with the risk of progression, our ability to accurately predict this risk remains limited. Our analysis demonstrated that the overall number of positive cores in the diagnostic and first surveillance biopsies is strongly associated with the risk of progression in active surveillance patients. Furthermore, combined results of diagnostic and first surveillance biopsies provide more information about the probability of progression than they do separately. The most important variable affecting the progression-free survival was the overall number of cores positive for cancer. By 3 years of active surveillance, most of the patients who had four positive cores in the diagnostic and surveillance biopsies progressed, while those who had only one positive core had an excellent prognosis. These findings could be used to improve the accuracy of assessments of the prognosis of patients with low-risk prostate cancer and to help them make informed decisions about their treatment. Objective To analyse the prognostic importance of information provided by the diagnostic biopsy, the first surveillance biopsy and a combination thereof to identify active surveillance patients with a particularly high risk of progression. Materials and Methods The present study included 161 active surveillance patients who had at least two surveillance biopsies. The first surveillance biopsy was performed within 1 year of the diagnosis. Further surveillance biopsies usually took place every 1–2 years. Progression on the surveillance biopsy was defined as the presence of Gleason 4/5 cancer, > two positive cores or >20% involvement of any core. Cox proportional hazards regression analysis was used to examine the relationship between biopsy characteristics and progression. Three distinct statistical models were built using characteristics of diagnostic biopsies, surveillance biopsies, and a combination thereof. Harrell's c-index was used to quantify the predictive accuracy of each multivariate Cox model. Results The median follow-up was 3.6 years; 46 (28.6%) patients progressed. In multivariate analysis the major factor associated with progression was the number of positive cores. The model based on the combined results of diagnostic and first surveillance biopsies was significantly more predictive than the models based on the individual results of each biopsy. Patients with four positive cores in the diagnostic and first surveillance biopsies had estimated 5-year progression rate of 100%. Conclusion The total number of positive cores in the diagnostic and first surveillance biopsies provides important information about the risk of prostate cancer progression in active surveillance patients.

The majority of patients with bladder cancer will be diagnosed following an episode of hematuria. With few exceptions, these patients should be referred for a complete urologic evaluation, including a history and physical examination, flexible cystoscopy, imaging of the upper urinary tract, and optional urine cytology. Those found to have a bladder tumor should undergo transurethral resection for the combined purposes of initial staging and treatment. Delays in diagnosing invasive bladder cancer are associated with adverse outcomes. In this review, we cover the diagnosis and management of bladder cancer. In addition, we discuss ways to improve outcomes through increased public awareness, improvements in tumor detection, accurate staging, and regimented patient surveillance.

Active surveillance is an established management option for patients with low risk prostate cancer. However, little is known about the characteristics associated with the increased probability of progression in patients on active surveillance. We analyzed our active surveillance cohort in search of such features.A total of 272 men with prostate cancer have enrolled in our active surveillance program since 1994, of whom 249 underwent at least 1 surveillance biopsy and were included in analysis. Our active surveillance inclusion criteria are biopsy Gleason grade less than 7, 2 or fewer positive biopsy cores, 20% or less tumor in any core and clinical stage T1-T2a. Changes in any of these parameters during followup that went beyond these limits were considered progression. Univariate and multivariate Cox regression analysis was done to determine patient characteristics associated with an increased risk of progression.A total of 64 patients (26%) showed progression at a median 2.9-year followup on a mean of 2.3 surveillance biopsies. The progression risk was significantly increased in black patients (adjusted HR 3.87-4.12), and in men with a smaller prostate and higher prostate specific antigen density. The latter 2 variables had no specific cutoff for an association with progression.Black men with low risk prostate cancer should be advised that the risk of progression on active surveillance may be higher than that in the available literature. Integral prognostic tools incorporating race and prostate specific antigen density may be useful to accurately assess the individual risk of progression in patients on active surveillance.

UNLABELLED What's known on the subject? and What does the study add? The surgical implications of renal cell carcinoma with coexisting bland and tumour thrombi of the inferior vena cava is not well described. In this study we review our experience managing these tumours. On multivariate analysis, we found that the presence of bland thrombus was associated with an increased need for surgical interruption of the inferior vena cava. OBJECTIVE • To study the role of interruption of the inferior vena cava (IVC) in patients with renal cell carcinoma (RCC) and associated bland and tumour thrombi. METHODS • We reviewed 129 consecutive patients with the preoperative diagnosis of RCC with tumour thrombus who underwent radical nephrectomy and tumour thrombectomy in one academic institution between May 1997 and February 2011. RESULTS • Percentages of patients with levels I, II, III and IV tumour thrombus were 29%, 13%, 48% and 9%, respectively. • The perioperative mortality rate was 2.3%. There were 29 (22%) perioperative complications recorded. • In all, 19 patients underwent surgical interruption of the IVC by ligation or segmental resection, including one level II, 14 level III and four level IV thrombi. • A total of 15 patients (12%) had bland thrombus associated with the tumour thrombus; four of these underwent intraoperative IVC filter placement and eight underwent surgical IVC interruption. • Advanced level of tumour thrombus was the only significant factor predicting association of bland thrombus (odds ratio [OR]= 2.09, 95% confidence interval [CI]: 1.082-4.037, P= 0.028). • On multivariate analysis, level of thrombus (OR = 3.1, 95% CI: 1.30-7.74, P= 0.011) and association of bland thrombus (OR = 9.07, 95% CI: 2.42-34.01, P= 0.001) were significant factors for IVC interruption. CONCLUSIONS • Surgical interruption of the IVC is a feasible option in selected patients with chronic IVC obstruction. Association of bland thrombus with tumour thrombus should alert the surgical team to the potential for a challenging surgery. • Precise preoperative imaging to assess the degree of venous obstruction and to help with differentiation between bland and tumour thrombus is key to achieving a surgical outcome with minimal morbidity.

BACKGROUND The purpose of our analysis was to determine if delays in treatment caused by active surveillance result in significant pathological changes when patients no longer meet the criteria on repeat biopsy and to study whether or not these changes may affect treatment outcomes. METHODS Out of 207 men who were on active surveillance, 47 (23%) no longer met the criteria after one of the repeat biopsies. Twenty-two underwent radical prostatectomy at our institution and formed the main group (Group 1) of this study. One hundred sixty-four patients met the criteria for active surveillance but underwent immediate surgery. Of these patients, we selected 38 (23%) with the lowest predicted biochemical recurrence-free survival. These patients formed the comparison group (Group 2). Pathological features as well as postoperative biochemical outcomes were compared between the groups. RESULTS Seven patients (32%) in Group 1 and four (11%) in Group 2 have predominantly high-grade cancer (i.e., ≥4/5 + 3) at pathology. The visually estimated percent of carcinoma was also higher in patients initially managed by active surveillance (median 12.5 vs. 5.0 in Groups 1 and 2, respectively, P = 0.009). Other pathological characteristics were similar in both groups. With limited duration of follow-up, postoperative biochemical recurrence-free survival did not differ significantly between the groups. CONCLUSIONS Our study has demonstrated that both tumor grade and volume may increase during active surveillance. However, the clinical significance of these changes with respect to the outcomes of delayed treatment remains to be established. Prostate 72:1573–1579, 2012. © 2012 Wiley Periodicals, Inc.

Molecular characterization of renal cell carcinoma may help differentiate benign oncocytoma from malignant renal cell carcinoma subtypes and predict metastasis. Chemokines, eg IL-8 and chemokine receptors such as CXCR4 and 7, promote inflammation and metastasis. SDF-1 is a CXCR4 and 7 ligand with 6 known isoforms. We evaluated the expression of these chemokines and chemokine receptors in kidney specimens.Using quantitative polymerase chain reaction we measured mRNA levels of IL-8, CXCR4 and 7, and SDF1 isoforms α, β and γ in a total of 166 specimens from 86 patients, including 86 tumor samples and 80 matched normal kidney samples. Mean ± SD followup was 18.9 ± 12 months (median 19.5). Renal cell carcinoma specimens included the clear cell, papillary and chromophobe subtype in 65, 10 and 5 cases, respectively, and oncocytoma in 6. A total of 17 cases were positive for metastasis.Median CXCR4 and 7, and SFD1-γ levels were increased twofold to tenfold. SDF1-α and β were unchanged or lower in clear cell renal cell carcinoma and papillary tumors than in normal tissue. Median SDF1-γ, IL-8, and CXCR4 and 7 were increased threefold to fortyfold in chromophobe tumors compared to oncocytoma. CXCR4 and 7 were increased in tumors less than 4 cm (mean 3,057 ± 2,230 and 806 ± 691) compared to oncocytoma (336 ± 325 and 201 ± 281, respectively, p ≤0.016). On multivariate analysis CXCR4 (p = 0.01), CXCR7 (p = 0.02) and SDF1-β (p = 0.005) were independently associated with metastasis. Combined CXCR7 plus SDF1-α and CXCR7 plus IL-8 markers showed the highest sensitivity (71% to 81%) and specificity (75% to 80%) of all individual or combined markers.Chemokines and chemokine receptors differentiate renal cell carcinoma and oncocytoma. Combined SDF1-α plus CXCR7 and IL-8 plus CXCR7 markers have about 80% accuracy for predicting renal cell carcinoma metastasis.

Context: Prostate cancer (PCa) remains an increasingly common malignancy worldwide. The optimal management of clinically localized, early-stage disease remains unknown, and profound quality of life issues surround PCa interventions. Objective: To systematically summarize the current literature on the management of low-risk PCa with active surveillance (AS), with a focus on patient selection, outcomes, and future research needs. Evidence acquisition: A comprehensive search of the PubMed and Embase databases from 1980 to 2011 was performed to identify studies pertaining to AS for PCa. The search terms used included prostate cancer and active surveillance or conservative management or watchful waiting or expectant management. Selected studies for outcomes analysis had to provide a comprehensive description of entry characteristics, criteria for surveillance, and indicators for further intervention. Evidence synthesis: Data from seven large AS series were reviewed. Inclusion criteria for surveillance vary among studies, and eligibility therefore varies considerably (4-82%). PCa-specific mortality remains low (0-1%), with the longest published median follow-up being 6.8 yr. Up to one-third of patients receive secondary therapy after a median of about 2.5 yr of surveillance. Surveillance protocols and triggers for intervention vary among institutions. Most patients are treated for histologic reclassification (27-100%) or prostate-specific antigen doubling time

Objective To analyze the diagnostic performance of individual prostate biopsy cores. The 12-core transrectal prostate biopsy scheme has emerged as a standard of care. However, quality of sampling may vary in different areas of the prostate included in this procedure. Material and Methods Two-hundred fifty men underwent radical prostatectomy at our institution. All participants had a systematic 12-core transrectal prostate biopsy containing lateral and medial cores from each side of the apical, medial and basal thirds of the prostate. Biopsy results were matched with histologic maps of the prostatectomy specimens. Sensitivity, negative predictive value (NPV), and overall accuracy were calculated for each biopsy core location and compared between different groups of cores. In addition, patients in the upper quartile of prostate weight were compared with the rest of the cohort. Results Sensitivity, NPV, and overall accuracy were significantly lower for apical cores. Average NPV and overall accuracy of basal and mid-lateral biopsies were inferior to those of medial biopsies on the same levels. However, sensitivity of these lateral cores was similar to that of the medial cores. Sensitivities of apical and mid cores were significantly lower in patients with larger prostates. Conclusion Decreased accuracy in lateral mid- and basal cores results from higher frequencies of cancer in corresponding prostate areas, and therefore additional samples should be taken at these locations. In addition, diagnostic accuracy of apical cores may be improved through better targeting of the prostatic apex. This may be particularly important in patients with larger prostates.