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Due to the lack of disease-specific symptoms, diagnosis and follow-up of bladder cancer has remained a challenge to the urologic community. Cystoscopy, commonly accepted as a gold standard for the detection of bladder cancer, is invasive and relatively expensive, while urine cytology is of limited value specifically in low-grade disease. Over the last decades, numerous molecular assays for the diagnosis of urothelial cancer have been developed and investigated with regard to their clinical use. However, although all of these assays have been shown to have superior sensitivity as compared to urine cytology, none of them has been included in clinical guidelines. The key reason for this situation is that none of the assays has been included into clinical decision-making so far. We reviewed the current status and performance of modern molecular urine tests following systematic analysis of the value and limitations of commercially available assays. Despite considerable advances in recent years, the authors feel that at this stage the added value of molecular markers for the diagnosis of urothelial tumors has not yet been identified. Current data suggest that some of these markers may have the potential to play a role in screening and surveillance of bladder cancer. Well-designed protocols and prospective, controlled trials will be needed to provide the basis to determine whether integration of molecular markers into clinical decision-making will be of value in the future.

Background The purpose of these clinical studies was to validate a Tissue Change Monitoring (TCM) algorithm in vivo. TCM is a quantitative tool for the real-time assessment of HIFU dose. TCM provides quantitative analysis of the backscatter pulse echo signals (pre and immediately post HIFU) for each individual ablative site, using ultrasonic tissue characterization as a surrogate for monitoring tissue temperature. Real-time analysis generates an energy difference parameter (ΔE in dB) that is proportional to tissue temperature. Methods Post in vitro studies, two clinical studies were conducted to validate the TCM algorithm on the Sonablate® device. Studies enrolled histologically confirmed, organ confined prostate cancer patients. The first clinical study was conducted in two phases for whole gland ablation. First eight patients’ data were used to measure the algorithm performance followed by 89 additional patients for long term outcome. The second clinical study enrolled five patients; four patients with focal cancer had hemi-ablation only and one had whole gland ablation. Four 3 Fr. needles containing three thermocouples each were placed transperineally in the prostate to record tissue temperatures in the focal zone, posterior to the focal zone and on the lateral gland where no HIFU was applied. Tissue temperatures from the focal zone were correlated to the ΔE parameter. Results In the first clinical study, the average TCM rate was 86%. Pre and 6 months post HIFU, median PSA was 7.64 and 0.025 ng/ml respectively and 97% patients had negative biopsy. For the second clinical study, the measured prostate tissue temperatures (Average, Max, and Min) in the ablation zones were 84°, 114° and 60 °C and the corresponding ΔE (dB/10) parameters were 1.05, 2.6 and 0.4 resulting in 83% of temperatures in the range of 75°-100 °C and 17% in the 60°-74 °C range. Outside the focal zone, the average temperature was 50 °C and in the lateral lobe where no HIFU was applied, peak temperature was 40.7 °C. Conclusions The TCM algorithm is able to estimate tissue changes reliably during the HIFU procedure for prostate tissue ablation in real-time and can be used as a guide for HIFU dose delivery and tissue ablation control.

Objective To define the role of multiparametric MRI (mpMRI) for treatment planning, guidance and follow-up in focal therapy for prostate cancer based on a multidisciplinary Delphi consensus project. Materials and Methods An online consensus process based on a questionnaire was circulated according to the Delphi method. Discussion points were identified by literature research and were sent to the panel via an online questionnaire in three rounds. A face-to-face consensus meeting followed the three rounds of questions that were sent to a 48-participant expert panel consisting of urologists, radiologists and engineers. Participants were presented with the results of the previous rounds. Conclusions formulated from the results of the questionnaire were discussed in the final face-to-face meeting. Results Consensus was reached in 41% of all key items. Patients selected for focal therapy should have biopsy-proven prostate cancer. Biopsies should ideally be performed after mpMRI of the prostate. Standardization of imaging protocols is essential and mpMRIs should be read by an experienced radiologist. In the follow-up after focal therapy, mpMRI should be performed after 6 months, followed by a yearly mpMRI. mpMRI findings should be confirmed by targeted biopsies before re-treatment. No consensus was reached on whether mpMRI could replace transperineal template saturation biopsies to exclude significant lesions outside the target lesion. Conclusions Consensus was reached on a number of areas related to the conduct, interpretation and reporting of mpMRI for use in treatment planning, guidance and follow-up of focal therapy for prostate cancer. Future studies, comparing mpMRI with transperineal saturation mapping biopsies, will confirm the importance of mpMRI for a variety of purposes in focal therapy for prostate cancer.

Objective To explore explanations for the numerical imbalance of biopsy-detected Gleason 8-10 prostate cancers (PCa) diagnosed in years 3-4 in the dutasteride and placebo groups of the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) study. Methods REDUCE was a 4-year, randomized, double-blind, placebo-controlled trial of dutasteride (0.5 mg/d) vs placebo for PCa risk reduction. We modeled the incidence of Gleason 8-10 cancer and used logistic regression analysis to evaluate the effects of baseline predictors of PCa, as well as post-baseline prostate volume at the time of biopsy, on PCa diagnosis. We compared needle biopsy Gleason scores with corresponding surgery Gleason scores. All statistical tests conducted were 2-sided. Results Had there been a scheduled biopsy occurring only at year 4, we estimated a similar incidence of Gleason 8-10 PCa in the dutasteride (n = 45) and placebo (n = 46) groups. Two biopsy Gleason 7 cancers in the placebo group (n = 150) were upgraded to Gleason 8-10 cancer on prostatectomy, and no patients in the dutasteride group (n = 111) were upgraded. Logistic regression analysis demonstrated the effect of prostate volume on Gleason 8-10 cancer diagnosis. Conclusion Although modeling of REDUCE data showed a similar incidence of Gleason 8-10 cancer in the dutasteride and placebo groups at year 4, an association between dutasteride and Gleason 8-10 cancer cannot be definitely excluded. It is likely that several biases, notably study design and prostate size at the time of biopsy, contributed to the numerical imbalance in Gleason 8-10 cancers observed between the treatment groups in years 3-4.

Item does not contain fulltext BACKGROUND: Metastatic castration-resistant prostate cancer (mCRPC) is a disease that primarily affects older men. Abiraterone acetate (AA), a selective androgen biosynthesis inhibitor, in combination with low-dose prednisone (P) improved overall survival (OS) in a randomised trial in mCRPC progressing after docetaxel versus placebo (PL) plus P. OBJECTIVE: To examine the efficacy and safety of AA plus P versus PL plus P in subgroups of elderly (aged >/=75 yr) (n=331) and younger patients (

To establish a consensus on the utility of multiparametric magnetic resonance imaging (mpMRI) to identify patients for focal therapy. Topics specifically not included staging of prostate cancer (PCa), but rather identifying the optimal requirements for performing MRI, and the current status of optimally performed mpMRI to a) determine focality of prostate cancer (i.e. localizing small target lesions of 0.5 cm3 and greater), b) to monitor and assess the outcome of focal ablation therapies, and c) to indentify the diagnostic advantages of new MRI methods. In addition, the need for transperineal template saturation biopsies in selecting patients for focal therapy was discussed, if a high quality mpMRI is available. In other words, can mpMRI replace the role of transperineal saturation biopsies in patient selection for focal therapy?Urological surgeons, radiologists, and basic researchers, from Europe and North America participated in a consensus meeting about the use of mpMRI in focal therapy of prostate cancer. The consensus process was face-to-face and specific clinical issues were raised and discussed with agreement sought when possible. All participants are listed among the authors.Consensus was reached on most key aspects of the meeting, however on definition of the optimal requirements for mpMRI, there was 1 dissenting voice. mpMRI is the optimum approach to achieve the objectives needed for focal therapy, if made on a high quality machine (3T with/without endorectal coil or 1.5 with endorectal coil) and judged by an experienced radiologist. Structured and standardized reporting of prostate MRI is paramount. State of the art mpMRI is capable to localize small tumors for focal therapy. State of the art mpMRI is the technique of choice for follow up of focal ablation.The present evidence for MRI in focal therapy is limited. mpMRI is not accurate enough to consistently grade tumor aggressiveness. Template guided saturation biopsies are no longer necessary when a high quality state of the art mpMRI is available, however, suspicious lesion should always be confirmed by (targeted) biopsy.

Purpose: The Post-Ureteroscopic Lesion Scale (PULS) offers a simple grading system for the description of ureteral lesions after ureteroscopy. In this article, we present the results of a video-based multicenter evaluation of the inter-rater reliability of clinically important PULS grades 0-3. Methods: Video sequences at the end of ureteroscopy (final passage) were recorded for 100 consecutive patients at a single institution and assessed by experienced urologists (n = 20) and senior residents (n = 17) at 19 international centers. The cohort included only patients with lesions grades 0-3 (with grades 2 and 3 subsumed as 2 + since distinction is defined by an extravasation of contrast medium in fluoroscopy). The gradings were evaluated for inter-rater reliability and in terms of simplicity, validity, comprehensibility, reproducibility, and usefulness. Results: Overall, inter-rater reliability was high (Kendall's W = 0.69, p < 0.001) and was comparable between specialists (Kendall's W = 0.69, p < 0.001) and residents (Kendall's W = 0.71, p < 0.001). The matched ratings showed grade 0 in 43.0 % of patients and grades 1 or 2 + in 44.0 and 13.0 % of patients, respectively. Results of the questionnaires indicated a high degree of acceptance, with an overall rating of 1.76 (1.64-1.93 for different items, scale 1-6). Conclusions: Inter-rater reliability of the endoscopically assessable PULS was high among urologists with different levels of experience in different countries worldwide. The validated PULS system may be used for standardized reporting of ureteral lesions/injuries after ureteroscopy. In addition, PULS will enable more selective standardization of indications for postoperative DJ stenting based on the randomized controlled trials.

Background: Several drugs are approved for the treatment of lower urinary tract symptoms (LUTS) in men, but these are mostly used by clinicians as monotherapies. The combination of different compounds, each of which targets a different aspect of LUTS, seems appealing. However, only few clinical trials have evaluated the effects of combination therapies. Objective: This systematic review analyzes the efficacy and adverse events of combination therapies for male LUTS. Evidence acquisition: PubMed and Cochrane databases were used to identify clinical trials and meta-analyses on male LUTS combination therapy. The search was restricted to studies of level of evidence >= 1b. A total of 49 papers published between January 1988 and March 2012 were identified. Evidence synthesis: The alpha(1)-adrenoceptor antagonist (alpha(1)-blocker)/5 alpha-reductase inhibitor (5-ARI) combination provides the most data. This combination seems to be more efficacious in terms of several outcome variables in patients whose prostate volume is between 30 ml and 40 ml when treatment is maintained for >1 yr; when given for 6 yr. The alpha(1)-blocker/muscarinic receptor antagonist (antimuscarinic) combination was most frequently assessed as an add-on therapy to already existing alpha(1)-blocker therapy. Inconsistent data derive from heterogeneous study populations and different study designs. Currently, the alpha(1)-blocker/antimuscarinic combination appears to be a second-line add-on for patients with insufficient symptom relief after monotherapy. The combination seems to be safe in men with postvoid residual 4 mo concerning safety and efficacy of this combination. The alpha(1)-blocker/phosphodiesterase type 5 inhibitor combination is a new treatment option with only preliminary reports. More studies are needed before definitive conclusions can be drawn. Conclusions: An alpha(1)-blocker/5-ARI combination is beneficial for patients whose prostate volume is between 30 ml and 40 ml when medical treatment is intended for >1 yr. Based on short-term follow-up studies, add-on of antimuscarinics to alpha(1)-blockers is an option when postvoid residual is

With the high prevalence of bothersome lower urinary tract symptoms (LUTS) in older men, clinical management has to be fairly simple and straightforward. In the absence of severe problems requiring immediate action, and after excluding possible other etiological factors by a simple diagnostic algorithm, the key parameter for therapeutic decisions is the severity of LUTS, in particular the degree of annoyance and irritation, and prostatic enlargement. Patients with bothersome LUTS request rapid improvement but also worry about possible deterioration, complications, and the need for surgery. With a prostate volume above 30–40 mL and/or prostate-specific antigen (PSA) serum >1.5 ng/mL, the combination of an alpha-1 blocker with a 5-alpha-reductase inhibitor (5-ARI) should be first-line treatment. With prostates

Botulinum toxin treatment has been investigated as a minimally invasive alternative to oral medications in men with lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (LUTS/BPH).To explore the efficacy of onabotulinumtoxinA 100 U, 200 U, and 300 U versus placebo in men with LUTS/BPH in a phase 2 dose-ranging study.A multicenter double-blind randomized, placebo-controlled 72-wk study enrolled men ≥ 50 yr of age with LUTS/BPH, International Prostate Symptom Score (IPSS) ≥ 12, total prostate volume (TPV) 30-100ml, and maximum flow rate (Q(max)) 5-15 ml/s.Single transperineal (n=63) or transrectal (n=311) administration of placebo (n=94) or onabotulinumtoxinA 100 U (n=95), 200 U (n=94), or 300 U (n=97) into the prostate transition zone.The primary efficacy end point was a change from baseline in IPSS at week 12. Secondary end points were Q(max), TPV, and transition zone volume (TZV). Analysis of covariance and the Cochran-Mantel-Haenszel method assessed the efficacy and proportion of IPSS responders. Adverse events (AEs) were assessed.Significant improvements from baseline in IPSS, Q(max), TPV, and TZV were observed for all groups, including placebo, at week 12 (p0.001), with no significant differences between onabotulinumtoxinA and placebo. However, in an exploratory post hoc analysis, a significant reduction in IPSS versus placebo was observed with onabotulinumtoxinA 200 U in prior α-blocker users (n=180) at week 12. AEs were comparable across all groups.Reductions in LUTS/BPH symptoms were seen in all groups, including placebo, with no significant between-group differences owing to a large placebo effect from the injectable therapy. The findings from the post hoc analysis in men previously treated with α-blockers will be further explored in an appropriately designed study.http://www.Clinical Trials.gov; NCT00284518.

Item does not contain fulltext BACKGROUND: Urinary prostate cancer antigen 3 (PCA3) assay in combination with established clinical risk factors improves the identification of men at risk of harboring prostate cancer (PCa) at initial biopsy (IBX). OBJECTIVE: To develop and validate internally the first IBX-specific PCA3-based nomogram that allows an individual assessment of a man's risk of harboring any PCa and high-grade PCa (HGPCa). DESIGN, SETTING, AND PARTICIPANTS: Clinical and biopsy data including urinary PCA3 score of 692 referred IBX men at risk of PCa were collected within two prospective multi-institutional studies. INTERVENTION: IBX (>/= 10 biopsy cores) with standard risk factor assessment including prebiopsy urinary PCA3 measurement. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: PCA3 assay cut-off thresholds were investigated. Regression coefficients of logistic risk factor analyses were used to construct specific sets of PCA3-based nomograms to predict any PCa and HGPCa at IBX. Accuracy estimates for the presence of any PCa and HGPCa were quantified using area under the curve of the receiver operator characteristic analysis and compared with a clinical model. Bootstrap resamples were used for internal validation. Decision curve analyses quantified the clinical net benefit related to the novel PCA3-based IBX nomogram versus the clinical model. RESULTS AND LIMITATIONS: Any PCa and HGPCa were diagnosed in 46% (n=318) and 20% (n=137), respectively. Age, prostate-specific antigen, digital rectal examination, prostate volume, and PCA3 were independent predictors of PCa at IBX (all p

Objective: This study aimed to validate, in a prospective, blinded, international and multicenter cohort, our previously reported four non-invasive tests for bladder cancer (BC) diagnosis based on the gene expression patterns of urine. Methods: Consecutive voided urine samples from BC patients and controls were prospectively collected in five European centres (n=789). Finally, 525 samples were successfully analysed. Gene expression values were quantified using TaqMan Arrays and previously reported diagnostic algorithms were applied to gene expression data. Results from the most accurate gene signature for BC diagnosis were associated with clinical parameters using analysis of variance test. Results: High diagnostic accuracy for the four gene signatures was found in the independent validation set (area under curve [AUC]=Z0.903-0.918), with the signature composed of two genes (GS_D2) having the best performance (sensitivity: 81.48%; specificity: 91.26%; AUC: 0.918). The diagnostic accuracy of GS_D2 was not affected by the number of tumours (p=0.58) but was statistically associated with tumour size (p=0.008). Also, GS_D2 diagnostic accuracy increases with increasing BC tumour risk. We found no differences in the performance of the GS_D2 test among the populations and centres in detecting tumours (p=0.7) and controls (p=0.2). Conclusions: Our GS_D2 test is non-invasive, non-observer dependent and non-labour-intensive, and has demonstrated diagnostic accuracy in an independent, international and multicenter study, equal or superior to the current gold standard (cystoscopy combined with cytology). Additionally, it has higher sensitivity than cytology while maintaining its specificity. Consequently, it meets the requirements for consideration as a molecular test applicable to clinical practice in the management of BC. (C) 2015 Elsevier Ltd. All rights reserved.

What's known on the subject? and What does the study add? Novel therapeutic methods have emerged in recent years as ‘focal’ treatment alternatives in which cancer foci can be eradicated and greatly reducing the associated side-effects of radical treatment. High-intensity focused ultrasound (HIFU) seems to result in a well fitted technology, which has proven short- to medium-term cancer control, with a low rate of complications comparable with those of established therapies. This is an up-to-date review of the available literature on HIFU as a definitive treatment of prostate cancer. It describes the technique in a comprehensive approach in terms of technical features, procedure, indications, and gives an overview of its historical background; finally, we present the future applications of HIFU and its development trend. OBJECTIVES • To provide an up-to-date review of the available literature on high-intensity focused ultrasound (HIFU) as a definitive treatment of prostate cancer. • To present the technique in a comprehensive approach, comparing the available devices according to the existing evidence in terms of technical features, procedure, indications, and to give an overview of its historical background; and finally, to discuss future applications of HIFU and its development trend. MATERIALS AND METHODS • A systematic literature search was conducted using MEDLINE and EMBASE via Ovid databases (January 2000 to December 2011), to identify studies on HIFU for treatment of prostate cancer. • Only English-language and human-based full manuscripts that reported on case series studies with >50 participants, patient characteristics, efficacy and safety data were included. RESULTS • No randomised controlled trials were identified by the literature search. We identified 31 uncontrolled studies that examined the efficacy of HIFU as primary treatment and two studies that examined the efficacy of HIFU as salvage treatment. • Most treated patients had localised prostate cancer (stage T1–T2); Gleason scores of 2–10 and mean prostate specific antigen (PSA) values of 4.6–12.7 ng/mL. The mean age range of the patients was 64.1–72 years. The mean follow-up ranged from 6.4 to 76.8 months. Negative biopsy rates ranged from 35 to 95%. PSA nadirs ranged from 0.04 to 1.8 ng/mL. The 5-year disease-free survival rates ranged from 61.2 to 95%; 7- and 8-year disease free survival rates ranged from 69 to 84%. • The most common complications associated with the HIFU procedure as the primary treatment included: urinary retention (

We studied the characteristics and prognosis of renal cell carcinoma (RCC) associated with Xp11.2 translocation and transcription factor E3 (TFE3) expression and determined the need for genetic analysis in routine diagnostics. Of 848 consecutive cases, 75 showed microscopic features suggestive of Xp11.2 translocation RCC or occurred in patients 40 years or younger. Of these cases, 17 (23%) showed strong nuclear TFE3 immunostaining, which was associated with more advanced tumors and inverse prognosis in univariate (P = .032) but not multivariate (P = .404) analysis. With fluorescence in situ hybridization and polymerase chain reaction, only 2 cases showed alterations of the X chromosome and the ASPL-TFE3 gene fusion, respectively. In our laboratory, the predictive value of TFE3 expression for the Xp11.2 translocation was 12%. Strong nuclear TFE3 expression is associated with metastatic spread and a poor prognosis. In our laboratory, TFE3 is not diagnostic for Xp11.2 translocation RCC. Diagnosis of Xp11.2 translocation RCC may be made only genetically.

What's known on the subject? and What does the study add? Focal therapy techniques are emerging in prostate cancer treatment. However, several key questions about patient selection, treatment and monitoring still have to be addressed. The concept of focal therapy is barely discussed in current urological guidelines. In the present manuscript, we report the results of a consensus meeting focused on ultrasonography, the most common used urological imaging method, in relation to focal therapy of prostate cancer. • To establish a consensus on the utility of ultrasonography (US) to select patients for focal therapy. Topics were the current status of US to determine focality of prostate cancer, to monitor and assess outcome of focal therapy and the diagnostic advantages of new US methods. In addition, the biopsy techniques required to identify focal lesions were discussed. • Urological surgeons, radiation oncologists, radiologists, and basic researchers from Europe and North America participated in a consensus meeting on the use of transrectal US (TRUS) in focal therapy of prostate cancer. The consensus process was face-to-face and specific clinical issues were raised and discussed with agreement sought when possible. • TRUS is commonly used and essential for diagnosing men with prostate cancer. It is particularly useful for targeting specific anatomical regions or visible lesions. However, it has several limitations and there is a need for improvement. Newer visualisation techniques, e.g. colour Doppler US, contrast-enhanced US and elastography, are being developed but currently there is no US technique that can accurately characterise a cancer suitable for focal therapy. Systematic biopsy is the only known procedure that allows the identification of prostate cancers suitable for focal therapy. Scarce data exist about the role of US for monitoring patients during or after ablative therapy. • Consensus was reached on all key aspects of the meeting. • US cannot reliably identify focal prostate cancer. New US methods show promising results in identifying prostate cancer focality. • Currently selecting appropriate candidates for focal therapy should be performed using dedicated protocols and biopsy schemes.

• The reported incidence of prostate cancer has risen since the implementation of screening. It is felt that the introduction of widespread prostate-specific antigen testing is responsible for most patients with prostate cancer now being diagnosed with asymptomatic, clinically localised disease. • Diagnosis at this stage is associated with significantly improved treatment outcomes and longer life expectancy. Although there is evidence that screening has reduced prostate cancer mortality, there is a risk of over-diagnosis and over-treatment of early state prostate cancers, including clinically insignificant and indolent cancers. • Active surveillance and focal therapy have been advocated as potential management options for some patients. However, these approaches face several challenges. Biopsy sampling errors together with less than optimal imaging of tumours can lead to difficulties in selecting suitable low-risk patients for these options. • To overcome these challenges, novel approaches to the staging and monitoring of patients with early prostate cancer are being developed. These include new imaging techniques, such as multi-parametric magnetic resonance imaging, and the development of new biomarkers and biopsy-based methods. These techniques aim to assess the potential of a specific tumour to be aggressive, and to improve patient outcomes. • The aim of the present paper is to summarise presentations and debates at the third annual Interactive Genitourinary Cancer Conference concerning the use of population-based screening methods and the roles of active surveillance and focal therapy as prostate cancer treatments. The application of novel imaging biopsy-based methods and biomarkers in early-stage prostate cancer will also be explored.

OBJECTIVE To evaluate the relationship between Prostate CAncer gene 3 (PCA3) and prostate cancer significance. PATIENTS AND METHODS Clinical data from two multi-centre European open-label, prospective studies evaluating the clinical utility of the PCA3 assay in guiding initial and repeat biopsy decisions were analysed. First-catch urine was collected after digital rectal examination (three strokes per lobe) and the PCA3 score was determined using the PROGENSA (R) PCA3 assay. Transrectal ultrasound-guided biopsy (>= 8 cores) and radical prostatectomy (RP) specimens were analysed by the local pathologist. The relationship between biopsy and RP outcomes with the PCA3 score was assessed. RESULTS Of the 1009 men enrolled, 348 (34%) had a positive biopsy. The median and mean PCA3 scores were statistically significantly lower in men with biopsy Gleason score = 7, with clinical stage T1c vs T2a-T2c, T3a cancers, with 33% positive biopsy cores and with 'biopsy indolent' vs 'biopsy significant' prostate cancer (indolent prostate cancer defined by biopsy Epstein criteria). In all, 175 men with a positive biopsy had a RP: median and mean PCA3 scores were statistically significantly lower in men with pathological Gleason score = 7, and with pathological stage T2a-T2c vs T3a-T3b cancers. CONCLUSIONS The PCA3 score may combined with traditional tools aid in identifying men with clinically insignificant prostate cancer, as shown by biopsy and RP pathological features including biopsy Epstein criteria, who could be candidates for active surveillance. Treatment selection should be based on a combination of clinical and pathological variables. If one wants to use a threshold point to guide treatment decisions in clinical practice, a PCA3 score threshold of 20 may have the highest utility for selecting men with clinically insignificant prostate cancer in whom active surveillance may be appropriate; a PCA3 score threshold of 50 may be used to identify men at high risk of harbouring significant prostate cancer who are candidates for RP. Although the association between the PCA3 score and prostate cancer aggressiveness needs further evaluation, the inclusion of the PCA3 score into patient management strategies may provide clinicians with another tool to more accurately determine the course of treatment

Context Prostate cancer (PCa) is the most common cancer in the adult male, and benign prostatic hyperplasia (BPH) represents the most frequent urologic diagnosis in elderly males. Recent data suggest that prostatic inflammation is involved in the pathogenesis and progression of both conditions. Objective This review aims to evaluate the available evidence on the role of prostatic inflammation as a possible common denominator of BPH and PCa and to discuss its possible clinical implication for the management, prevention, and treatment of both diseases. Evidence acquisition The National Library of Medicine Database was searched for the following Patient population, Intervention, Comparison, Outcome (PICO) terms: male, inflammation, benign prostatic hyperplasia, prostate cancer, diagnosis, progression, prognosis, treatment, and prevention. Basic and clinical studies published in the past 10 yr were reviewed. Additional references were obtained from the reference list of full-text manuscripts. Evidence synthesis The histologic signature of chronic inflammation is a common finding in benign and malignant prostate tissue. The inflammatory infiltrates are mainly represented by CD3 + T lymphocytes (70–80%, mostly CD4), CD19 or CD20 B lymphocytes (10–15%), and macrophages (15%). Bacterial infections, urine reflux, dietary factors, hormones, and autoimmune response have been considered to cause inflammation in the prostate. From a pathophysiologic standpoint, tissue damage associated with inflammatory response and subsequent chronic tissue healing may result in the development of BPH nodules and proliferative inflammatory atrophy (PIA). The loss of glutathione S-transferase P1 (GSTP1) may be responsible in patients with genetic predisposition for the transition of PIA into high-grade intraepithelial neoplasia (HGPIN) and PCa. Although there is growing evidence of the association among inflammatory response, BPH, and PCa, we can only surmise on the immunologic mechanisms involved, and further research is required to better understand the role of prostatic inflammation in the initiation of BPH and PCa. There is not yet proof that targeting prostate inflammation with a pharmacologic agent results in a lower incidence and progression or regression of either BPH or PCa. Conclusions Evidence in the peer-reviewed literature suggested that chronic prostatic inflammation may be involved in the development and progression of chronic prostatic disease, such as BPH and PCa, although there is still no evidence of a causal relation. Inflammation should be considered a new domain in basic and clinical research in patients with BPH and PCa.

Study Type – Prognostic (RCT) Level of Evidence 1b What's known on the subject? and What does the study add? Previous studies used the decrease in PSA after 6 months of dutasteride treatment as a new ‘baseline’ PSA value from which subsequent rises may serve as a warning for prostate cancer; however, PSA tends to continue to decrease as dutasteride treatment continues. By comparing positive biopsy rates in the REDUCE study using any rise from nadir in the dutasteride arm and standard PSA decision criteria (NCCN) in the placebo arm, we demonstrated that the ability to detect prostate cancer and high grade prostate cancer is maintained with dutasteride treatment. OBJECTIVES • To determine if dutasteride-treated men can be monitored safely and adequately for prostate cancer based on data from the Reduction by Dutasteride in Prostate Cancer Events (REDUCE) study. • To analyse whether the use of treatment-specific criteria for repeat biopsy maintains the usefulness of prostate-specific antigen (PSA) level for detecting high grade cancers. PATIENTS AND METHODS • The REDUCE study was a randomized, double-blind, placebo-controlled investigation of whether dutasteride (0.5 mg/day) reduced the risk of biopsy-detectable prostate cancer in men with a previous negative biopsy. • The usefulness of PSA was evaluated using biopsy thresholds defined by National Comprehensive Cancer Network guidelines in the placebo group and any rise in PSA from nadir (the lowest PSA level achieved while in the study) in the dutasteride group. • The number of cancers detected on biopsy in the absence of increased/suspicious PSA level as well as sensitivity, specificity, positive predictive value and negative predictive value for high grade prostate cancer detection were analysed by treatment group. • Prostate cancer pathological characteristics were compared between men who did and did not meet biopsy thresholds. RESULTS • Of 8231 men randomized, 3305 (dutasteride) and 3424 (placebo) underwent at least one prostate biopsy during the study and were included in the analysis. • If only men meeting biopsy thresholds underwent biopsy, 25% (47/191) of Gleason 7 and 24% (7/29) of Gleason 8–10 cancers would have been missed in the dutasteride group, and 37% (78/209) of Gleason 7 and 22% (4/18) Gleason 8–10 cancers would have been missed in the placebo group. • In both groups, the incidence of Gleason 7 and Gleason 8–10 cancers generally increased with greater rises in PSA. • Sensitivity of PSA kinetics was higher and specificity was lower for the detection of Gleason 7–10 cancers in men treated with dutasteride vs placebo. • Men with Gleason 7 and Gleason 8–10 cancer meeting biopsy thresholds had greater numbers of positive cores, percent core involvement, and biopsy cancer volume vs men not meeting thresholds. CONCLUSION • Using treatment-specific biopsy thresholds, the present study shows that the ability of PSA kinetics to detect high grade prostate cancer is maintained with dutasteride compared with placebo in men with a previous negative biopsy. • The sensitivity of PSA kinetics with dutasteride was similar to (Gleason 8–10) or higher than (Gleason 7–10) the placebo group; however, biopsy decisions based on a single increased PSA measurement from nadir in the dutasteride group resulted in a lower specificity compared with using a comparable biopsy threshold in the placebo group, indicating the importance of confirmation of PSA measurements.

BACKGROUND The prognostic relevance of the amount of extraprostatic cancer spread in nerves in prostate cancer patients is not well established. METHODS Eighty-eight patients were included in our study with pT3a pN0 M0 R0 prostate cancer treated with retropubic prostatectomy. Eighty-seven of them showed perineural invasion, 54 were confined to the prostate, 33 showed cancer spread in extraprostatic nerves, which was quantified by counting each transverse section of nerves infiltrated by cancer in totally embedded specimens. Biochemical relapse was established by serum PSA levels of ≥0.2 ng/ml as well as PSA ≥ 0.4 ng/ml and higher according to the EAU guidelines. RESULTS Extraprostatic but not intraprostatic perineural infiltration was significantly more often found in tumors of higher Gleason score. Intraprostatic number of infiltrated nerves (NIN) correlated with extraprostatic NIN. There was no association between extraprostatic or intraprostatic NIN and Gleason score, lymphatic, or blood vessel invasion. Extraprostatic neural infiltration in ≤10 nerves extended relapse free survival in univariate analysis for PSA 0.2 and 0.4 ng/ml (P = 0.002 and P

BACKGROUND: Several studies have demonstrated that abnormal levels of nuclear matrix protein 22 (NMP22) are associated with bladder cancer and have led to the approval of NMP22 as a urinary biomarker by the US Food and Drug Administration. Nonetheless, the clinical significance of NMP22 remains unclear. The objective of this study was to use decision analysis to determine whether NMP22 improves medical decision-making. METHODS: The current study included 2222 patients who had a history of nonmuscle-invasive bladder cancer and current negative cytology. The authors developed models to predict cancer recurrence or progression to muscle-invasive disease using voided NMP22 levels, cystoscopy, age, and sex. Clinical net benefit was calculated by summing the benefits (true-positives), subtracting the harms (false-positives), and weighting these values by the threshold probability at which a patient or clinician would opt for cytoscopy. RESULTS: After cystoscopy, 581 patients (26%) had cancer identified. The NMP22 level was associated significantly with bladder cancer recurrence and progression (P 8% for recurrence and > 3% for progression. Only offering cystoscopy to those who had a risk > 15% reduced the number of cystoscopies by 229 while missing only 25 cancer recurrences per 1000 men with negative cytology. The current study was limited by its multicenter design. CONCLUSIONS: For clinicians who would perform a cystoscopy at a threshold of 5% for recurrence or 1% for progression, NMP22 did not aid clinical decision-making. For less risk-averse clinicians who would only perform a cystoscopy at a threshold probability >thinsp;8% for recurrence or > 3% for progression, NMP22 helped to indicate which patients required cystoscopy and which could be spared this procedure. Cancer 2011. © 2011 American Cancer Society.

Study Type – Prognosis (RCT) Level of Evidence 1b What’s known on the subject? and What does the study add? Sexual dysfunction is a common problem in elderly men, especially if they also have LUTS. Serum testosterone likewise decreases with aging, and a common conclusion from this is that low serum testosterone levels are a main cause for this. This is by far the largest population-based study correlating sexual dysfunction with serum testosterone levels. Whereas age, body mass index and the severity of LUTS were independent risk factors for sexual dysfunction, serum testosterone levels were not. Treating sexual dysfunction only based on a low serum testosterone level therefore appears unjustified. There is a trend towards sexual dysfunction with S. testosterone levels 60 years) and a negative prostate biopsy within 6 months of enrolment. • Baseline values (mean serum testosterone, age, International Prostate Symptom Score [IPSS], total prostate volume [TPV], body mass index [BMI], and presence of diabetes/glucose intolerance) were compared in subjects with and without sexual dysfunction (sexual inactivity, impotence, decreased libido or a Problem Assessment Scale of the Sexual Function Index [PAS-SFI] score

Purpose of review To assess the current status of open partial nephrectomy (OPN) for the treatment of renal tumors. Recent findings Today, the standard indications for open nephron-sparing surgery are renal tumors in solitary kidneys, bilateral renal masses, tumors in patients with impaired renal function and unilateral masses smaller than 4 cm in diameter with a normal functioning contralateral kidney. For the latter, OPN is increasingly being challenged by laparoscopic partial nephrectomy, which in the hands of experts appears to achieve comparable oncological results, although at a higher complication rate. In selected situations, OPN appears justified in intermediate-risk patients with tumors up to 7 cm in diameter. Long-term outcome data indicate that OPN has cancer-free survival rates comparable to those of radical surgery with better preservation of renal function, decreased overall mortality and reduced frequency of cardiovascular events. Summary OPN remains the standard of care for small renal masses and is increasingly advocated in selected patients with tumors up to 7 cm in diameter.

We developed and externally validated a prognostic nomogram specifically for papillary renal cell carcinoma.We retrospectively studied 435 patients who underwent radical or partial nephrectomy for papillary renal cell carcinoma at 3 institutions. Slides were reviewed by 1 uropathologist per institution. We constructed a nomogram predicting 5-year disease specific survival as a graphic representation of significant variables on multivariate Cox proportional hazards regression analysis using data on 258 patients from 2 of the 3 institutions. Nomogram discrimination and calibration were assessed by bootstrapping to obtain relatively unbiased estimates. External validation was done in 177 patients from a third institution.At a median 50.8-month followup 77 papillary renal cell carcinoma related deaths had occurred. In the multivariate Cox proportional hazards model incidental detection, T classification, M classification, vascular invasion and tumor necrosis extent were retained as independent prognostic factors of disease specific survival and formed the basis of the nomogram. The nomogram predicted well with a 93.6% bootstrapped corrected concordance index and showed good calibration. External independent validation revealed 94.2% predictive accuracy.We developed a highly accurate tool specifically for papillary renal cell carcinoma using basic clinical and pathological information to predict disease specific survival. This tool should be helpful to identify papillary renal cell carcinoma with aggressive clinical behavior and may contribute to the ability to individualize postoperative surveillance and therapy.

Study Type – Therapy (case series) Level of Evidence 4 OBJECTIVE To outline the features and outcomes of renal cell carcinoma (RCC) in native kidneys of renal transplant recipients, who are at increased risk of developing this disease. PATIENTS AND METHODS We retrospectively studied the clinicopathological features and survival of 28 surgically treated RCCs, which developed in 24 renal transplant recipients. Features and outcomes were compared with 671 patients with RCC who had no renal transplant. RESULTS The median interval between renal transplantation and the occurrence of RCC was 5.6 years. Acquired cystic kidney disease was present in 83% of the transplanted patients. Compared with the patients with RCC and no renal transplant, RCCs of native kidneys in transplant recipients were more frequently incidental findings (92% vs 77%, P = 0.092), multifocal (39% vs 15%, P

Study Type – Diagnosis (exploratory cohort) Level of Evidence 2b OBJECTIVE To describe the follow-up of men with an elevated ‘Prostate CAncer gene 3’ (PCA3, a promising novel tool for prostate cancer detection) and a negative repeat biopsy (Bx-), as a previous study in men with one or two negative Bx (Bx−) scheduled for repeat Bx showed that a higher PCA3 score corresponded with a higher probability of a positive repeat Bx (Bx+). PATIENTS AND METHODS This study comprised an analysis of the follow-up of men with a PCA3 score of ≥20 and a repeat Bx−, after which a follow-up Bx was taken. The initial study data in 463 men were also analysed to compare characteristics of: (i) men with a PCA3 score of ≥20 and ≥35 and a repeat Bx+, vs those with a Bx−; and (ii) men with a repeat Bx− and a PCA3 score of ≥20 vs

Study Type – Diagnosis (exploratory cohort) Level of Evidence 2b OBJECTIVE To determine the performance characteristics of the prostate cancer gene 3 (PCA3) score on the outcome of biopsy relative to different ranges of free-to-total prostate-specific antigen (PSA) ratio (f/tPSA) in men with a previous negative biopsy and a PSA level of 2.5–10 ng/mL, as urine tests like PCA3 are currently under investigation in order to improve prostate cancer diagnosis and to decrease the rate of unnecessary rebiopsies. PATIENTS AND METHODS Data from the previous prospective European multicentre study were reviewed. Only patients with a PSA level of 2.5–10 ng/mL were included in the present study. In all, 301 patients had complete data. The diagnostic accuracy of the PCA3 score for predicting a positive biopsy outcome was studied using sensitivity, specificity, negative and positive predictive values. The PCA3 performance was evaluated relative to three different subgroups of f/tPSA, as follows: >20% (group 1), 10–20% (group 2) and 30, vs 10.3%, 15.5% and 28.6% when the PCA3 score was 30 was a significant independent predictor of positive biopsies (odds ratio 3.01; 95% confidence interval 1.74–5.23; P < 0.001). CONCLUSIONS PCA3 remained a better predictor of prostate cancer than f/tPSA. In men with a f/tPSA of >10%, the use of the PCA3 score was highly correlated with the risk of having cancer on re-biopsy, and could prevent unnecessary prostate biopsies if the value is low.

The landmark Prostate Cancer Prevention Trial (PCPT) generated interest in the potential health benefits and cost of reducing prostate cancer risk—specifically, the potential role of 5α-reductase inhibitors. However, the PCPT raised several unanswered questions, including the cause and significance of the increased incidence of high-grade tumors associated with finasteride. In the present study, we review the PCPT findings and unanswered questions, next steps in this field, and ongoing prostate cancer prevention trials addressing these unanswered questions. Particular emphasis is placed on the design of the second large-scale trial of a 5α-reductase inhibitor, the REduction by DUtasteride of prostate Cancer Events (REDUCE) trial.

We outlined the putative significance of GST in renal cell carcinoma biology by investigating the influence of its deletion polymorphisms on renal cell carcinoma progression.Genomic DNA was purified from peripheral blood leukocytes. GSTM1 and GSTT1 genes were polymerase chain reaction amplified and gene fragments were separated by agarose gel electrophoresis. Intact GSTM1 and GSTT1 alleles were identified by the presence of 230 and 480 bp fragments, respectively. Genotypes were associated with clinicopathological variables and survival.Of 147 patients with renal cell carcinoma 80 (54%) had the GSTM1 null and 27 (18%) had the GSTT1 null genotype. The GST genotype distribution did not differ significantly from that in 112 controls without renal cell carcinoma. However, the GSTM1 null genotype was associated with 60% lower odds of the papillary subtype (OR 0.40, 95% CI 0.18 to 0.92, p = 0.032), lower Fuhrman grade (chi-square 9.77, p = 0.008) and a lower risk of metastatic disease in patients with the clear cell subtype (chi-square 4.48, p = 0.034). Of patients with the clear cell subtype those with the GSTM1 null genotype had improved cancer specific survival (p = 0.0412). GSTT1 did not correlate with any pathological variable except age at renal cell carcinoma onset since patients with renal cell carcinoma and the GSTT1 null genotype were significantly younger than their counterparts (mean +/- SD age 58.5 +/- 14.2 vs 65.4 +/- 12.8 years, p = 0.016).GSTM1 deletion polymorphism impacts renal cell carcinoma histological subtype, Fuhrman grade and metastatic behavior while GSTT1 deletion leads to renal cell carcinoma onset at a younger age. In patients with clear cell renal cell carcinoma the GSTM1 null genotype may be associated with better prognosis.

Study Type – Prognosis (case series) Level of Evidence 4 OBJECTIVE To examine the association between the delay from diagnosis of upper-tract urothelial carcinoma (UTUC) to radical nephroureterectomy (RNU), and the pathological features and outcomes, as the decision to proceed to RNU for an individual patient is complex. PATIENTS AND METHODS The records of 187 patients who had RNU were reviewed; the interval from diagnosis to RNU was analysed as both a continuous (months) and categorical variable (

Study Type – Prognosis (retrospective cohort) Level of Evidence 2b OBJECTIVE To externally validate the prognostic value of lymphovascular invasion (LVI) in a large international cohort of patients treated with radical cystectomy (RC) for urothelial carcinoma of the bladder (UCB). PATIENTS AND METHODS We collected data from 4257 patients treated with RC and pelvic lymphadenectomy for UCB, without neoadjuvant chemotherapy, at 12 centres. LVI was defined as presence of nests of tumour cells within an endothelium-lined space. RESULTS LVI was detected in 1407 patients (33.1%); the proportion of LVI increased with advancing stage, higher grade, soft-tissue surgical margin involvement, and lymph node metastasis (P < 0.001 for all). In standard multivariate models, LVI was associated with both disease recurrence (hazard ratio 1.43, P < 0.001) and cancer-specific mortality (1.45, P < 0.001). In the entire cohort, adding LVI to a base model that included standard features improved only minimally its predictive accuracy for both recurrence and cancer-specific mortality (by 1.1% and 1.2%, respectively). In 3122 patients with negative lymph nodes, LVI remained independently associated with and improved the predictive accuracy of the standard predictors for recurrence (hazard ratio 1.68, P < 0.001; +2.3%) and cancer-specific mortality (1.70, P < 0.001; +2.4%). By contrast, in 1071 node-positive patients, LVI only marginally improved the prediction of cancer-specific recurrence (hazard ratio 1.20, P < 0.001; +0.2%) and survival (1.23, P < 0.001; +0.5%). CONCLUSIONS LVI is strongly associated with clinical outcome in node-negative patients treated with RC. The assessment of LVI might help to identify patients who could benefit from adjuvant therapy after RC. After confirmation in different populations, LVI should be included in the staging of UCB.

Context The incidence of renal cell carcinomas (RCCs) has increased steadily—most rapidly for small renal masses (SRMs). Paralleling the changing face of RCC in the past 2 decades, new, less invasive surgical options have been developed. Laparoscopic radical nephrectomy (LRN) is an established procedure for the treatment of RCC. Treatment of SRMs includes open partial nephrectomy (OPN), laparoscopic partial nephrectomy (LPN), thermal ablation, and active surveillance. Objective To present an overview of minimally invasive treatment options and data on surveillance for kidney cancer. Evidence acquisition Literature and meeting abstracts were searched using the terms renal cell carcinoma, minimally invasive surgery, laparoscopic surgery, thermal ablation, surveillance, and robotic surgery. The articles with the highest level of evidence were identified with the consensus of all the collaborative authors and reviewed. Evidence synthesis Renal insufficiency, as measured by the glomerular filtration rate, occurs more often after radical nephrectomy than partial nephrectomy (PN). OPN and LPN show comparable results in long-term oncologic outcomes. The treatment modality for SRMs should therefore be nephron-sparing surgery (NSS). In select patients, thermal ablation or active surveillance of SRMs is an alternative. Conclusions LRN has become the standard of care for most organ-confined tumours not amenable to NSS. Amongst NSS options, PN is the treatment of choice, yet remains underutilised in the community. Initial data during its learning curve revealed that LPN had higher urologic morbidity. However, current emerging data indicate that in experienced hands, LPN has shorter ischaemia times, a lower complication rate, and equivalent long-term oncologic and renal functional outcomes, yet with decreased patient morbidity compared to OPN. Robotic partial nephrectomy is being explored at select centres, and cryotherapy and radiofrequency ablation are options for carefully selected tumours. Active surveillance is an option for selected high-risk patients. Percutaneous needle biopsy is likely to gain increasing relevance in the management of small renal tumours.

Context: The immunology of the prostate has developed into a new field of research in urology. The leukocyte population increases are not yet fully understood, but it has been demonstrated that most resected prostate tissue shows signs of inflammatory response. Objective: This article reviews recent findings and discusses the complex mechanisms involved in the prostatic inflammatory response and the immunologic functions of the prostate, and the roles the prostatic inflammatory response in the cause of prostate disease such as benign prostatic hyperplasia (BPH). Evidence acquisition: We performed a search of the medical literature with PubMed, using keywords such as prostate cancer, inflammation of the prostate, leukocytes, estrogen, and cytokine and genetic expression of inflammation. Articles and data were reviewed as to their relevance, and inclusion and exclusion criteria were determined prospectively. Evidence synthesis: Evidence showing that inflammation of the prostate plays a role in prostate cancer (PCa) is mounting. Different types of inflammation exist and are distinguished according to the distribution and location of leukocytes and the histology of the surrounding tissue. Most resected prostate tissue shows signs of inflammatory response, and a relationship between T-cell infiltration and stromal proliferation can be found. Evidence for the importance of estrogen and proinflammatory cytokine interleukin (IL; IL-6, IL-8, IL-15, IL-17) also can be found. Early stages of investigation of the immunologic function of the prostate show that both prostatic epithelial and stromal cells express members of the toll-like receptor family and are therefore capable of recognizing foreign incoming antigens. Conclusions: Although this area of study is new, the immunology and inflammatory responses of the prostate are seen as important components of further study of prostate diseases such as PCa and BPH. Data supporting the role of immunology and activated leukocytes in malignant cells are also an important finding and can possibly lead to new knowledge about malignant cells.

Background The advantage of photodynamic diagnosis in detecting urothelial cell carcinoma (UCC) of the bladder has been demonstrated clearly, but it comes at the price of a higher false-positive rate. Optical coherence tomography (OCT) is a noninvasive, real-time, microstructural imaging modality that uses near-infrared light for a point analysis of the bladder-wall microstructure. Objective To evaluate whether adding targeted OCT analysis of lesions that are suspicious at white-light (WL) and hexaminolevulinate (HAL) fluorescence cystoscopy improves diagnostic accuracy in the detection of UCC. Design, setting, and participants In this prospective single-center study with same-patient comparison, patients with suspected UCC first received an intravesical instillation of HAL. Cystoscopy was performed in WL, followed by blue-light inspection and OCT scanning. Intervention Suspicious lesions identified by WL or HAL were evaluated by OCT and were subsequently resected or biopsied. Measurements We measured changes in sensitivity and specificity in detecting UCC using WL, HAL, and targeted OCT. Results and limitations In 66 patients studied, 232 lesions were detected, were scanned by OCT, and were subsequently resected or biopsied. Additionally, 132 areas of normal-appearing urothelium were investigated by all three methods and biopsied. On a per-lesion basis, sensitivity and specificity were respectively 69.3% and 83.7% for WL, 97.5% and 78.6% for HAL, and 97.5% and 97.9% for HAL combined with OCT. Overall, UCC was diagnosed in 58 patients (87.9%), with a per-patient sensitivity of 89.7% for WL and 100% for both HAL alone and HAL with targeted OCT. Per-patient specificity for HAL alone and targeted HAL was 62.5% and 87.5%, respectively. The limitation of OCT results from poor visualization of flat lesions in WL, making scanning a time-consuming procedure. Conclusions Combining fluorescence cystoscopy with targeted OCT increases the specificity of fluorescence cystoscopy significantly, with no added morbidity, and reduces the need for unnecessary (false-positive) biopsies.

BACKGROUND: Low morbidity has been advocated for cryoablation of small renal masses. OBJECTIVES: To assess negative perioperative outcomes of laparoscopic renal cryoablation (LRC) with ultrathin cryoprobes and patient, tumour, and operative risk factors for their development. DESIGN, SETTING, AND PARTICIPANTS: Prospective collection of data on LRC in five centres. INTERVENTION: LRC. MEASUREMENTS: Preoperative morbidity was assessed clinically and the American Society of Anaesthesiologists (ASA) score was assigned prospectively. Charlson Comorbidity Index (CCI) and Charlson-Age Comorbidity Index (CACI) scores were retrospectively assigned. Negative outcomes were prospectively recorded and defined as any undesired event during the perioperative period, including complications, with the latter classed according to the Clavien system. Patient, tumour, and operative variables were tested in univariate analysis as risk factors for occurrence of negative outcomes. Significant variables (p or = 3. Multivariate analysis showed that tumour size in centimetres, the presence of cardiac conditions, and female gender were independent predictors of negative perioperative outcomes occurrence. Receiver operator characteristic curve confirmed the tumour size cut-off of 3.4 cm as an adequate predictor of negative outcomes. CONCLUSIONS: Perioperative negative outcomes and complications occur in 17% and 15.5%, respectively, of cases treated by LRC with multiple ultrathin needles. Most of the complications are Clavien grade 1 or 2. The presence of cardiac conditions, female gender, and tumour size are independent prognostic factors for the occurrence of a perioperative negative outcome

In 2006, prostate cancer accounted for approximately 20% of all noncutaneous cancers detected in European men, placing it at the top of the list of diagnosed cancers [1]. Incidence rates of prostate cancer have risen dramatically across Europe in the last 2 decades but still vary by a factor of up to 4 in the different European countries (Figs. 1 and 2). This difference is clearly due to the variable use of early detection approaches, particularly prostate-specific antigen (PSA) screening, in asymptomatic patients. Surprisingly, although higher prostate cancer incidence has always been accompanied by profound stage and grade shifts [2], mortality rates across Europe do not reflect this variability (Fig. 1). This becomes even more apparent when adding the corresponding figures from the United States, with incidence and mortality rates of 173.8 and 30.3, respectively, per 100 000 men (in 2002) [3].

Objective To investigate the spontaneous variation of leukocytospermia (>1 million/mL) in semen samples from infertile men. Design Prospective cohort study. Setting Andrologic clinic at university hospital. Patient(s) Ninety-nine men evaluating for infertility causes. Intervention(s) Two semen analyses according the World Health Organization criteria combined with urologic investigation without any treatment. Main Outcome measure(s) Spontaneous (downward/upward) variation in leukocyte count, sperm concentration, total motility, and morphology between the two semen samples. Result(s) In the first semen analysis, 21% of men had leukocytospermia. By the second analysis, leukocyte concentrations were within the normal range in 9 of these 21 men, corresponding to a downward variation of 43%. In contrast, 7 of 78 patients with normal leukocyte levels at the first analysis had leukocytospermia at the second analysis, corresponding to an upward variation of 9%. The upward variation rates for sperm concentration, total motility, and morphology were 4%, 17%, and 4%, respectively. Downward variation rates were considerably higher for total motility and morphology (30% and 28%, respectively). Conclusion(s) The rate for spontaneous downward variation of leukocytospermia in the absence of treatment was 43% in this study. This rate should be taken into consideration when treating infertile men with leukocytospermia, because effective medical therapy is still lacking.

OBJECTIVES High-grade prostate cancer is associated with low serum testosterone levels, which generally recover after radical prostatectomy. The cause of this low testosterone level is unclear, and it has been hypothesized that cancer cells produce a factor that disturbs the pituitary-gonadal axis. Inhibin is a hormone that has a negative feedback effect on this axis. The aim of this study was to investigate the role of serum inhibin in patients with prostate cancer. METHODS The serum hormone levels of the pituitary-gonadal axis, including inhibin levels, in patients with prostate cancer were compared with those in patients with benign prostatic hyperplasia. Testosterone levels of less than 3 ng/mL were classified as hypogonadal. Prostate cancer was classified according to Gleason score as high grade (Gleason score 7 to 10) or low grade (Gleason score 2 to 6). RESULTS A total of 196 men (126 with prostate cancer and 70 with benign prostatic hyperplasia) were entered into the study. The serum inhibin levels did not differ significantly between the patients with benign prostatic hyperplasia and those with prostate cancer (150.0 versus 131.75 pg/mL, P = 0.062), between men with hypogonadal and eugonadal disease (143.0 versus 146.5 pg/mL, P = 0.573), or between those with low-grade and high-grade cancer (151.5 versus 146.0 pg/mL, P = 0.830). Men with high-grade cancer had lower levels of serum testosterone than did those with low-grade cancer (3.49 versus 4.09 ng/mL, P = 0.056). CONCLUSIONS The results of our study have shown that although high-grade prostate cancer is associated with low serum testosterone levels, inhibin does not appear to be the cause of this phenomenon.

Background Serum prostate-specific antigen (PSA) is a standard method and a widely used marker for prostate cancer, but it has a poor specificity for early detection. Herein we demonstrate that intracellular macrophage PSA (imPSA) enables screening and differentiation between benign and malignant prostate disease. Materials and Methods The efficacy of intracellular macrophage PSA in circulating and tissue macrophages was therefore investigated in a double-centre study of 38 prostate cancer patients and 36 healthy controls by fluorescent-activated cell sorting analysis and immunohistology. Results Both methods uncovered the existence of PSA-positive macrophages specific for patients with prostate cancer. In addition, we demonstrate the superiority of our new test over standard serum total PSA in a blinded double-centre trial. ImPSA had a marked higher sensitivity and specificity than serum total PSA (imPSA: sensitivity 92%, specificity 92%, positive predictive value 92%; serum total PSA: sensitivity 79·5%, specificity 87·5%, positive predictive value 26·8%). Conclusion In this study, we demonstrate that imPSA is a new prostate cancer screening method that is highly sensitive and more specific than standard PSA testing.

Objective High-intensity focused ultrasound (HIFU) permits targeted homogeneous ablation of tissue. The objective of this phase 1 study was to evaluate the feasibility of HIFU ablation of small renal tumours under laparoscopic control. Patients and methods Ten kidneys with solitary renal tumours were treated with a newly developed 4.0MHz laparoscopic HIFU probe. In the first two patients with 9-cm tumours, a defined marker lesion was placed prior to laparoscopic radical nephrectomy. In eight patients with a mean tumour size of 22mm (range, 11–40), the tumour was completely ablated as in curative intent, followed by laparoscopic partial nephrectomy in seven tumours. One patient had post-HIFU biopsies and was followed radiologically. Specimens were studied by detailed and whole-mount histology, including NADH stains. Results Mean HIFU insonication time was 19min (range, 8–42), with a mean targeted volume of 10.2cm 3 (range, 9–23). At histological evaluation both marker lesions showed irreversible and homogeneous thermal damage within the targeted site. Of the seven tumours treated and removed after HIFU, four showed complete ablation of the entire tumour. Two had a 1- to 3-mm rim of viable tissue immediately adjacent to where the HIFU probe was approximated, and one tumour showed a central area with about 20% vital tissue. There were no intra- or postoperative complications related to HIFU. Conclusion The morbidity of laparoscopic partial nephrectomy mainly comes from the need to incise highly vascularized parenchyma. Targeted laparoscopic HIFU ablation may render this unnecessary, but further studies to refine the technique are needed.

OBJECTIVE: To assess the value of nuclear matrix protein-22 (NMP22), compared with urinary cytology, in predicting the recurrence of bladder cancer that is not transitional cell carcinoma (non-TCC). PATIENTS AND METHODS: We tested the sensitivity, specificity and the predictive accuracy of NMP22 in the context of non-TCC bladder cancer recurrence, and compared it to the performance of urinary cytology. The study group comprised 2687 patients with history of non-muscle-invasive bladder cancer from 10 centres across four continents. RESULTS: The mean patient age was 64.8 years and 75.4% were men; of all patients, 513 (19.1%) had positive urinary cytology, 906 (33.7%) had a positive NMP22 test (

Aims: Benign prostatic hyperplasia (BPH) is a bothersome disease that can progress if left untreated. However, patient and urologist perspectives on BPH management are not fully understood. The aim of the Prostate Research on Behaviour and Education (PROBE) Survey was to assess healthcare-seeking behaviour and attitudes to BPH treatment in 502 BPH patients, and the beliefs and management practices of 100 urologists, from France, Germany, Italy, Spain and the UK. Results: The principal concerns of patients seeking medical advice were fear of cancer, sleep disruption, discomfort or embarrassment. The majority of BPH patients recalled receiving a digital rectal examination (61%), routine prostate-specific antigen (PSA) tests (67%) and prescription medication (72%). Eighty per cent of 5 alpha-reductase inhibitor (5ARI) users vs. 68% of alpha-blocker users were satisfied with their treatment. More than half of the patients were concerned about requiring surgery or developing acute urinary retention, and > 75% would prefer a drug that provides reduction in the risk of surgery than one that provides rapid symptom relief. Most urologists performed digital rectal examinations (96%) and PSA tests (71%) on > 90% of patients presenting with BPH symptoms. Eighty-seven per cent of urologists believe that BPH progresses, and 78% believe that 5ARIs prevent BPH progression. However, most urologists prescribe alpha-blockers while few prescribe 5ARIs. Conclusions: This study highlights discrepancies between views and beliefs of patients and physicians regarding BPH and current practice in Europe.