EffectiveNess of a multimodal preHAbilitation program in patieNts with bladder canCEr undergoing radical cystectomy: protocol of the ENHANCE multicentre randomised controlled trial.

INTRODUCTION: Radical cystectomy (RC) is the standard treatment for patients with non-metastatic muscle-invasive bladder cancer, as well as for patients with therapy refractory high-risk non-muscle invasive bladder cancer. However, 50-65% of patients undergoing RC experience perioperative complications. The risk, severity and impact of these complications is associated with a patient's preoperative cardiorespiratory fitness, nutritional and smoking status and presence of anxiety and depression. There is emerging evidence supporting multimodal prehabilitation as a strategy to reduce the risk of complications and improve functional recovery after major cancer surgery. However, for bladder cancer the evidence is still limited. The aim of this study is to investigate the superiority of a multimodal prehabilitation programme versus standard-of-care in terms of reducing perioperative complications in patients with bladder cancer undergoing RC. METHODS AND ANALYSIS: This multicentre, open label, prospective, randomised controlled trial, will include 154 patients with bladder cancer undergoing RC. Patients are recruited from eight hospitals in The Netherlands and will be randomly (1:1) allocated to the intervention group receiving a structured multimodal prehabilitation programme of approximately 3-6 weeks, or to the control group receiving standard-of-care. The primary outcome is the proportion of patients who develop one or more grade ≥2 complications (according to the Clavien-Dindo classification) within 90 days of surgery. Secondary outcomes include cardiorespiratory fitness, length of hospital stay, health-related quality of life, tumour tissue biomarkers of hypoxia, immune cell infiltration and cost-effectiveness. Data collection will take place at baseline, before surgery and 4 and 12 weeks after surgery. ETHICS AND DISSEMINATION: Ethical approval for this study was granted by the Medical Ethics Committee NedMec (Amsterdam, The Netherlands) under reference number 22-595/NL78792.031.22. Results of the study will be published in international peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT05480735.

Human polyomaviruses JCPyV and MCPyV in urothelial cell carcinoma: a single institution experience.

Objective: Urothelial cell carcinoma (UCC) is the most common type of urinary bladder. JCPyV and BKPyV have been detected in the urine and tissue of urothelial cell carcinomas (UCC) in immunocompetent patients. Here, we investigated the presence of several HPyVs in UCC samples using diverse molecular techniques to study the prevalence of HPyVs in UCC. Methods: A large single-institution database of urine cytology specimens (UCS; n = 22.867 UCS) has previously been searched for decoy cells (n = 30), suggesting polyomavirus infection. The available urine sediments and formalin-fixed paraffin-embedded (FFPE) tissue samples of UCC patients were tested for the presence of JCPyV-LTAg expression by immunohistochemistry (IHC) labeled with SV40-LTAg antibody (clone: PAb416) and subsequent PCR followed by sequencing. In addition, the presence of the oncogenic Merkel cell polyomavirus (MCPyV) and the presence of human polyomavirus 6 (HPyV6) and 7 (HPyV7) DNA were tested with DNA PCR or IHC. Results: Of the 30 patients harboring decoy cells, 14 were diagnosed with UCC of the urinary bladder (14/30; 46.6%) before presenting with decoy cells in the urine. The SV40-LTAg IHC was positive in all 14 UCC urine sediments and negative in the FFPE tissues. JCPyV-DNA was identified in all five available UCS and in three FFPE samples of UCC (three of 14; 21.4%). Two UCC cases were positive for MCPyV-DNA (two of 14; 14.3%), and one of them showed protein expression by IHC (one of 14; 7.1%). All specimens were HPyV6 and HPyV7 negative. Conclusion: Our findings show the presence of JCPyV in the urine and UCC of immunocompetent patients. Moreover, MCPyV was detected in two UCC cases. In total, five UCC cases showed the presence of either JCPyV or MCPyV. The evidence here supports the hypothesis that these viruses might sporadically be associated with UCC. Further studies are needed to confirm the relevance of JCPyV or MCPyV as a possible risk factor for UCC development.

Quality appraisal of clinical guidelines for recurrent urinary tract infections using AGREE II: a systematic review.

INTRODUCTION AND HYPOTHESIS: Recommendations for preventing and diagnosing recurrent urinary tract infection (UTI) tend to vary between clinical practice guidelines (CPGs) because of low-quality scientific evidence, potentially leading to practice variation and suboptimal care. We assessed the quality of existing CPGs for recurrent UTI. METHODS: A systematic search was performed from January 2000 to June 2021 in PubMed and EMBASE for CPGs on recurrent UTI prevention or hospital diagnostics in Dutch, English, and Spanish. Each CPG was assessed by four appraisers in a multidisciplinary review team, using the Appraisal of Guidelines, Research, and Evaluation II (AGREE II) instrument. RESULTS: We identified and assessed eight CPGs published between 2013 and 2021. The scope and purpose (mean and standard deviation: 67.3 ± 21.8) and clarity of presentation (74.8 ± 17.6) domains scored highly. However, issues with methods, patient participation, conflict of interests, and facilitators and barriers were common and resulted in lower scores for the rigour of development (56.9 ± 25.9), applicability (19.6 ± 23.4), stakeholder involvement (50.4 ± 24.6), and editorial independence (62.1 ± 23.1) domains. Overall, two CPGs were recommended, three were recommended with modifications, and three were not recommended. CONCLUSIONS: Significant room for improvement exists in the quality of CPGs for recurrent UTI, with most displaying serious limitations in the stakeholder involvement, rigour of development, and applicability domains. These aspects must be improved to decrease diagnostic and therapeutic uncertainty. Developers could benefit from using checklists and following guidelines when developing de novo CPGs.

Predictive Factors in Sacral Neuromodulation: A Systematic Review.

INTRODUCTION: Sacral neuromodulation (SNM) is an effective treatment in patients with overactive bladder syndrome or nonobstructive urinary retention when conservative treatment fails. Several factors that could impact outcome with SNM have been studied. This systematic review investigated these predictive factors and their relevance for clinical practice. METHODS: Systematic review according to the PRISMA guidelines was conducted. This review is registered in the PROSPERO register (CRD42015016256). RESULTS: Seventy-eight studies (of which 11 abstracts) were included. Females, younger patients, and a tined lead procedure tend to be predictive in successful SNM outcome. Factors that did not influence SNM outcome were prior back surgery, surgery for stress urinary incontinence, affective symptoms, and duration of complaints. Reduced detrusor contractility is associated with a lower success rate. The level of evidence of most studies (graded according to the Centre for Evidence-Based Medicine) was 3b. CONCLUSION: Even though this systematic review investigated predictive factors (gender, age, type of procedure, type of lead, and detrusor contractility), no general consensus on predictive factors could be made. Most studies are small, retrospective, and involve a heterogeneous population. Therefore, prospective research in larger specific patient groups remains necessary to find predictors of SNM outcome.

Comparison of the diagnostic yield of routine versus indicated flowmetry, ultrasound and cystoscopy in women with recurrent urinary tract infections.

INTRODUCTION AND HYPOTHESIS: To quantify and compare the outcomes of routine vs. urologist-requested diagnostic testing for recurrent urinary tract infections (rUTI). METHODS: A retrospective cohort study of patients with rUTI referred to a large non-academic teaching hospital between 2016 and 2018 (Hospital A) and a university hospital between 2014 and 2016 (Hospital B). Electronic medical records were reviewed for baseline and diagnostic data. Women underwent the following assessments routinely: urinalysis, voiding diary, flowmetry in Hospital A and urinalysis, voiding diary, flowmetry, ultrasound, abdominal x-ray and cystoscopy in Hospital B. All other diagnostics were performed by indication in each hospital. RESULTS: We included 295 women from Hospital A and 298 from Hospital B, among whom the mean age (57.6 years) and mean UTI frequency (5.6/year) were comparable, though more were postmenopausal in Hospital A. We identified abnormalities by flowmetry or post-void residual volumes in 134 patients (Hospital A: 79; Hospital B: 55), cystoscopy in 14 patients (Hospital A: 6; Hospital B: 8) and ultrasound in 42 patients (Hospital A: 16; Hospital B: 26), but these differences were not significant. Diagnostics altered treatment in 117 patients (e.g., pelvic floor muscle training, referral to another specialist, surgical intervention), mostly due to flowmetry and post-void residual volume measurement. The retrospective design and absence of follow-up data limit these results. CONCLUSIONS: The routine use of cystoscopy and ultrasound in female patients with rUTIs should not be recommended as they yield few abnormalities and lead to additional costs.

Development of a Management Algorithm for Acute and Chronic Radiation Urethritis and Cystitis.

OBJECTIVE: The purpose of this review was to summarize the current literature on the assessment and treatment of radiation urethritis and cystitis (RUC) for the development of an evidenced-based management algorithm. MATERIAL AND METHODS: The PubMed/MEDLINE database was searched by a multidisciplinary group of experts in January 2021. RESULTS: In total, 48 publications were identified. Three different types of RUC can be observed in clinical practice: inflammation-predominant, bleeding-predominant, and the combination of inflammation- and bleeding-RUC. There is no consensus on the optimal treatment of RUC. Inflammation-predominant RUC should be treated symptomatically based on the existence of bothersome storage or voiding lower urinary tract symptom as well as on pain. When bleeding-predominant RUC has occurred, hydration and hyperbaric oxygen therapy (HOT) should be used first and, if HOT is not available, oral drugs instead (sodium pentosane polysulfate, aminocaproic acid, immunokine WF 10, conjugated estrogene, or pentoxifylline + vitamin E). If local bleeding persists, focal therapy of bleeding vessels with a laser or electrocoagulation is indicated. In case of generalized bleeding, intravesical installation should be initiated (formalin, aluminium salts, and hyaluronic acid/chondroitin). Vessel embolization is a less invasive treatment with potentially less complications and good clinical outcomes. Open- or robot-assisted surgery is indicated in patients with permanent, life-threatening bleeding, or fistulae. CONCLUSIONS: Treatment of RUC, if not self-limiting, should be done according to the type of RUC and in a stepwise approach. Conservative/medical treatment (oral and topic agents) should primarily be used before invasive (transurethral) treatments.

Modeling-Based Decision Support System for Radical Prostatectomy Versus External Beam Radiotherapy for Prostate Cancer Incorporating an In Silico Clinical Trial and a Cost-Utility Study.

The aim of this study is to build a decision support system (DSS) to select radical prostatectomy (RP) or external beam radiotherapy (EBRT) for low- to intermediate-risk prostate cancer patients. We used an individual state-transition model based on predictive models for estimating tumor control and toxicity probabilities. We performed analyses on a synthetically generated dataset of 1000 patients with realistic clinical parameters, externally validated by comparison to randomized clinical trials, and set up an in silico clinical trial for elderly patients. We assessed the cost-effectiveness (CE) of the DSS for treatment selection by comparing it to randomized treatment allotment. Using the DSS, 47.8% of synthetic patients were selected for RP and 52.2% for EBRT. During validation, differences with the simulations of late toxicity and biochemical failure never exceeded 2%. The in silico trial showed that for elderly patients, toxicity has more influence on the decision than TCP, and the predicted QoL depends on the initial erectile function. The DSS is estimated to result in cost savings (EUR 323 (95% CI: EUR 213-433)) and more quality-adjusted life years (QALYs; 0.11 years, 95% CI: 0.00-0.22) than randomized treatment selection.

Current Management of Post-radical Prostatectomy Urinary Incontinence.

Prostate cancer is the second most common cancer in men worldwide. Radical prostatectomy and radiation beam therapy are the most common treatment options for localized prostate cancer and have different associated complications. The etiology of post prostatectomy incontinence is multifactorial. There is evidence in the literature that anatomic support and pelvic innervation are important factors in the etiology of post-prostatectomy incontinence. Among the many surgical and technical factors proposed in the literature, extensive dissection during surgery, damage to the neurovascular bundle and the development of postoperative fibrosis have a substantial negative impact on the continence status of men undergoing RP. Sparing of the bladder neck and anterior, and possibly posterior, fixation of the bladder-urethra anastomosis are associated with better continence rates. Overactive bladder syndrome (OAB) is multifactorial and the exact role of prostate surgery in the development of OAB is still under debate. There are several variables that could contribute to detrusor overactivity. Detrusor overactivity in patients after radical prostatectomy has been mainly attributed to a partial denervation of the bladder during surgery. However, together with bladder denervation, other hypotheses, such as the urethrovesical mechanism, have been described. Although there is conflicting evidence regarding the importance of conservative treatment after post-prostatectomy urinary incontinence, pelvic floor muscle training (PFMT) is still considered as the first treatment choice. Duloxetin, either alone or in combination with PFMT, may hasten recovery of urinary incontinence but is often associated with severe gastrointestinal and central nervous side effects. However, neither PFMT nor duloxetine may cure male stress urinary incontinence. The therapeutic decision and the chosen treatment option must be individualized for each patient according to clinical and social factors. During the recent years, the development of new therapeutic choices such as male sling techniques provided a more acceptable management pathway for less severe forms of urinary incontinence related to radical prostatectomy. Following this perspective, technological improvements and the emergence of new dedicated devices currently create the premises for a continuously positive evolution of clinical outcomes in this particular category of patients.

Is prostate cancer radiotherapy using implantable rectum spacers safe and effective in inflammatory bowel disease patients?

BACKGROUND: Prostate cancer radiotherapy (RT) in patients with (active) inflammatory bowel disease (IBD) remains controversial. We hypothesized that RT in combination with a biodegradable prostate-rectum spacer balloon implantation, might be a safe treatment approach with acceptable toxicities for these high risk for rectal toxicity patients. MATERIALS AND METHODS: We report on a small prospective mono-centric series of 8 patients with all-risk prostate cancer with the comorbidity of an IBD. Four patients had Crohn's disease and 4 patients had ulcerative colitis. One out of four had an active status of IBD. All patients were intended to be treated with curative high-dose RT: 5 patients were treated with external beam RT (70 Gray (Gy) in 28 fractions), and 3 patients were treated with 125I-implant (145 Gy). Toxicities were scored according to the CTCAE v4.03: acute side effects occur up to 3 months after RT, and late side effects start after 3 months. RESULTS: Median follow-up was 13 months (range: 3-42 months). Only one acute grade 2 gastro-intestinal (GI) toxicity was observed: an increased diarrhea (4-6 above baseline) during RT, which resolved completely 6 weeks after treatment. No late grade 3 or more GI toxicity was reported, and no acute and late grade ≥2 genitourinary toxicity events were observed. CONCLUSION: Prostate cancer patients with IBD are a challenge to treat with RT. Our results suggest that RT in combination with a balloon implant in selective patients with (active) IBD may be promising, however additional validation is needed.

Clinical Efficacy of Serenoa repens Versus Placebo Versus Alpha-blockers for the Treatment of Lower Urinary Tract Symptoms/Benign Prostatic Enlargement: A Systematic Review and Network Meta-analysis of Randomized Placebo-controlled Clinical Trials.

CONTEXT: International guidelines do not make any specific recommendations on Serenoa repens (SeR) for the treatment of male lower urinary tract symptoms (LUTS) secondary to benign prostatic enlargement (BPE), due to product heterogeneity and methodological limitations of the published trials and meta-analyses. OBJECTIVE: We aimed to compare the clinical efficacy of hexanic extract of SeR (HESr) versus non-HESr (nHESr) versus placebo versus alpha-blockers (ABs) in patients affected by LUTS secondary to BPE through a network meta-analysis method. EVIDENCE ACQUISITION: The search was conducted until December 31, 2018 using Medline, Scopus, and Web of Science databases without restriction. We included randomized controlled trials (RCTs) with at least one comparison between SeR, ABs, or placebo for the treatment of LUTS/BPE. Outcomes of the study were the mean change in the International Prostate Symptom Score (IPSS) and peak flow (PF). This systematic review has been registered on PROSPERO (CRD42018084360). EVIDENCE SYNTHESIS: In total, 2115 articles were identified. After the global assessment, 22 RCTs matched with the inclusion criteria, including 8564 patients. For IPSS, the mean efficacies against placebo were +0.48 and -1.69 for HESr and nHESr, respectively, at 3 mo; 0.59 for nHESr at 6 mo; and -1.31 and -3.30 for nHESr and HESr, respectively, at 12 mo. For PF, the mean efficacies against placebo were +0.53 and +2.82 for HESr and nHESr, respectively, at 3 mo; +1.85 for nHESr at 6 mo; and +4.05 and +5.52 for HESr and nHESr, respectively, at 12 mo. Based on the surface under the cumulative ranking curve rankograms, terazosin showed the highest score (99.6%), while alfuzosin, tamsulosin, silodosin, HESr, and nHESr showed scores of 53.7%, 42.3%, 68.5%, 36.7%, and 47.3%, respectively. CONCLUSIONS: In this network meta-analysis, we demonstrated that SeR did not show clinically meaningful improvement in LUTS and PF. PATIENT SUMMARY: In the present study, we found no clinically meaningful improvement of Serenoa repens for the treatment of lower urinary tract symptoms/benign prostatic enlargement. The analysis showed that the benefit over placebo was minimal and may not justify its clinical use before higher level of evidence will be available.

Long-term Follow-up of Intravesical Onabotulinum Toxin-A Injections in Male Patients with Idiopathic Overactive Bladder: Comparing Surgery-naïve Patients and Patients After Prostate Surgery.

BACKGROUND: Evidence regarding long-term results in male idiopathic overactive bladder (iOAB) patients is limited and rarely focuses on the effects of prior prostatic surgery. OBJECTIVE: This study aims to identify the long-term treatment persistency and occurrence of adverse events of intravesical onabotulinum toxin-A (BoNT-A) injections in male iOAB patients after prostatic surgery (ie, transurethral resection of the prostate [TURP] or radical prostatectomy [RP]) compared with surgery-naïve patients. DESIGN, SETTING, AND PARTICIPANTS: In this retrospective, single-centre study, data from 477 patients treated with intravesical BoNT-A injections were collected. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Outcome data of 120 male patients with iOAB, with collectively 207 BoNT-A injections, were analysed and presented in this study. RESULTS AND LIMITATIONS: At the last point of follow-up, 35 patients (29.2%) were still on active treatment. Twenty patients (16.7%) required de novo clean intermittent self-catheterisation (CISC). Three groups were identified: 56 patients without prostate surgery, 40 patients with TURP, and 24 patients with RP prior to treatment. Discontinuation rates and patient-reported outcomes of BoNT-A treatment (none, insufficient, or satisfactory) were similar, but a significant difference was seen in de novo CISC (p=0.004): 28.6% in the group without prior surgery, 7.5% in the TURP subgroup, and 4.2% in the RP subgroup. Odds of de novo CISC was significantly higher for the group without prior surgery than for both the TURP subgroup (odds ratio [OR] 4.9; 95% confidence interval [CI]: 1.33-18.31; p=0.017) and the RP subgroup (OR 9.2; 95% CI: 1.14-73.96; p= 0.037). CONCLUSIONS: The data of this retrospective, single-centre cohort suggest that BoNT-A treatment leads to lower CISC rates in male patients after prior desobstructive surgery than in surgery-naïve patients. PATIENT SUMMARY: This study describes the results of onabotulinum toxin-A (BoNT-A) injections in the bladder of male patients with idiopathic overactive bladder after initial prostate surgery compared with surgery-naïve patients. The results showed that BoNT-A treatment leads to lower catheterisation rates in patients after prior prostate surgery than in men without prior prostate surgery.

Sacral nerve stimulation for refractory OAB and idiopathic urinary retention: Can phenotyping improve the outcome for patients: ICI-RS 2019?

AIMS: Sacral nerve stimulation (SNS) is widely used to treat refractory idiopathic overactive bladder (OAB) and idiopathic urinary retention. However, clinical outcomes are variable and understanding predictive factors for success or side-effects would enable personalization of therapy and optimization of outcomes. At the International Consultation on Incontinence-Research Society meeting 2019, a Think Tank was convened to discuss how advances in the basic science study of SNS may be translatable into clinical practice to improve outcomes of patients undergoing SNS treatment. METHODS: We conducted a literature review and expert consensus meeting focusing on current methods of phenotyping patients and specifically, how advances in basic science research of the mechanism of action of SNS can be translated into clinical practice to improve patient selection for therapy. RESULTS: The terms "Idiopathic OAB" and "idiopathic urinary retention" encompass several underlying pathophysiological phenotypes. Commonly, phenotyping is based on clinical and urodynamic factors. Animal studies have demonstrated that high-frequency stimulation can produce rapid onset, reversible conduction block in peripheral nerves. Altering stimulation parameters may potentially enable personalization of therapy depending upon the clinical indication in the future. Similarly, advances in conditional and closed-loop stimulation may offer greater efficacy for certain patients. Phenotyping based on psychological comorbidity requires further study to potentially optimize patient selection for therapy. CONCLUSIONS: Idiopathic OAB and idiopathic urinary retention are heterogenous conditions with multiple potential underlying phenotypes. Tailoring stimulation parameters to the needs of each individual according to phenotype could optimize outcomes. Assessing psychological comorbidity may improve patient selection. Areas for further research are proposed.

Can multicentre urodynamic studies provide high quality evidence for the clinical effectiveness of urodynamics? ICI-RS 2019.

AIMS: Lower urinary tract (LUT) function can be investigated by urodynamic studies (UDS) to establish underlying functional abnormalities in the LUT. A multicentre registry could present an opportunity to improve the scientific evidence base for UDS. During the International Consultation on Incontinence Research Society (ICI-RS) meeting in Bristol, United Kingdom 2019, an expert panel discussed the potential of a multicentre urodynamic registry to improve the quality of urodynamic output. METHODS: the potential importance of a multicentre urodynamic registry, parameter inclusion, quality control, and pitfalls during a registry roll-out were reviewed and discussed. RESULTS AND CONCLUSIONS: The clinical utility, evaluation, and effectiveness of UDS remain poorly defined due to a lack of high quality evidence and large study populations. Therefore, the ICI-RS proposes formation of a urodynamic panel for future roll-out of a registry. The inclusion of basic parameters was discussed and the essential parameters were defined as well as the potential pitfalls of a registry roll-out. The discussion and recommendations in this paper form the base for future urodynamic registry development.

The Role of Urinary Microbiota in Lower Urinary Tract Dysfunction: A Systematic Review.

CONTEXT: Until 2012, the urinary tract of healthy individuals was considered to be sterile. The advent of metagenomic sequencing revealed a unique urinary microbiota (UM). This paradigm shift appears to have prolific implications in the etiology of several functional lower urinary tract (LUT) disorders. OBJECTIVE: To systematically summarize recent data on the role of UM in LUT dysfunction. EVIDENCE ACQUISITION: We performed a critical review according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement. We conducted a search on PubMed/MEDLINE and SCOPUS with the following MESH terms/keywords: "Microbiome OR Microbiota AND (urinary disorder OR urinary tract symptom OR overactive bladder OR urinary incontinence OR interstitial cystitis OR chronic prostatitis)." The range of search was placed between January 2010 and April 2018, and articles with no full text available or those not written in English were excluded. All retrieved papers were first reviewed by title and abstract, yielding a total of 303 papers. Additional manuscripts, such as those referenced by reviews, were further included. Thirty-six publications were included. EVIDENCE SYNTHESIS: Analysis by 16S rRNA sequence and expanded quantitative urine culture provided evidence for the presence of live bacteria in urine, nondetectable by standard culture protocols. Moreover, differences in the UM between healthy individuals and patients with LUT dysfunction were demonstrated. CONCLUSIONS: In the near future, urologists must consider urinary dysbiosis as a possible cause of different functional LUT disorders, with potential clinical implications in their diagnosis and treatment. PATIENT SUMMARY: Development of metagenomic sequencing revealed a unique urinary microbiota nondetectable by standard culture protocols. This systematic review summarizing recent data on the role of urinary microbiota in lower urinary tract (LUT) dysfunction supports urinary dysbiosis as a possible cause of different functional LUT disorders.

Exhaled-breath Testing for Prostate Cancer Based on Volatile Organic Compound Profiling Using an Electronic Nose Device (Aeonose™): A Preliminary Report.

BACKGROUND: Prostate biopsy, an invasive examination, is the gold standard for diagnosing prostate cancer (PCa). There is a need for a novel noninvasive diagnostic tool that achieves a significantly high pretest probability for PCa, reducing unnecessary biopsy numbers. Recent studies have shown that volatile organic compounds (VOCs) in exhaled breath can be used to detect different types of cancers via training of an artificial neural network (ANN). OBJECTIVE: To determine whether exhaled-breath analysis using a handheld electronic nose device can be used to discriminate between VOC patterns between PCa patients and healthy individuals. DESIGN, SETTING, AND PARTICIPANTS: This prospective pilot study was conducted in the outpatient urology clinic of the Maastricht University Medical Center, the Netherlands. Patients with histologically proven PCa were already included before initial biopsy or during follow-up, with no prior treatment for their PCa. Urological patients with negative biopsies in the past year or patients with prostate enlargement (PE) with low or stable serum prostate-specific antigen were used as controls. Exhaled breath was probed from 85 patients: 32 with PCa and 53 controls (30 having negative biopsies and 23 PE). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Patient characteristics were statistically analyzed using independent sample t test and Pearson's chi-square test. Data analysis was performed by Aethena software after data compression using the TUCKER3 algorithm. ANN models were trained and evaluated using the leave-10%-out cross-validation method. RESULTS AND LIMITATIONS: Our trained ANN showed an accuracy of 0.75, with an area under the curve of 0.79 with sensitivity and specificity of 0.84 (95% confidence interval [CI] 0.66-0.94) and 0.70 (95% CI 0.55-0.81) respectively, comparing PCa with control individuals. The negative predictive value was found to be 0.88. The main limitation is the relatively small sample size. CONCLUSIONS: Our findings imply that the Aeonose allows us to discriminate between patients with untreated, histologically proven primary PCa and control patients based on exhaled-breath analysis. PATIENT SUMMARY: We explored the possibility of exhaled-breath analysis using an electronic nose, to be used as a noninvasive tool in clinical practice, as a pretest for diagnosing prostate cancer. We found that the electronic nose was able to discriminate between prostate cancer patients and control individuals.

Botulinum toxin A for refractory OAB and idiopathic urinary retention: Can phenotyping improve outcome for patients: ICI-RS 2019?

AIMS: Botulinum toxin A (BTX-A) is a well-established treatment for refractory idiopathic overactive bladder (OAB). It has also been used with short-term success in treating idiopathic urinary retention. However, efficacy and complication rates are variable and predicting those likely to benefit most from treatment would enable personalization of therapy and optimization of outcomes. At the International Consultation on Incontinence-Research Society (ICI-RS) meeting in 2019 a Think Tank addressed the question of how we can improve the way we phenotype patients undergoing BTX-A treatment. METHODS: The Think Tank conducted a literature review and expert consensus meeting focussing on how advances in basic science research of the mechanism of action of BTX-A, as well as assessment of psychological comorbidity, can be translated into clinical practice to improve patient selection for therapy. RESULTS: Idiopathic OAB and idiopathic urinary retention are heterogenous conditions encompassing several phenotypes with multiple potential pathophysiological mechanisms. Animal models have demonstrated a central nervous system mechanism of action of intravesically injected BTX-A and this has been confirmed in human functional MRI studies, but whether this tool can be used to predict outcome from treatment remains to be determined. Phenotyping based on psychological comorbidity using validated screening tools should be studied as a way to potentially optimize patient selection for therapy. CONCLUSIONS: Advances in basic science research into the mechanism of action of BTX-A have improved our understanding of the pathophysiology of OAB and may lead to novel ways to phenotype patients. Psychological assessment is another way in which phenotyping may be improved. Areas for further research are proposed.

How can we prevent postprostatectomy urinary incontinence by patient selection, and by preoperative, peroperative, and postoperative measures? International Consultation on Incontinence-Research Society 2018.

AIMS: To review current prevention strategies for urinary incontinence among patients undergoing radical prostatectomy (RP). METHODS: This is a consensus report of the proceedings of a research proposal from the annual International Consultation on Incontinence-Research Society (ICI-RS), 14 to 16 June 2018 (Bristol, UK): "How can we prevent postprostatectomy incontinence by patient selection, and by preoperative, peroperative, and postoperative measures?" RESULTS: Several baseline parameters were proposed as predicting factors for postprostatectomy urinary incontinence (PPUI), including age, tumor stage, prostate volume, preoperative lower urinary tract symptoms, maximum urethral closure pressure, and previous transurethral resection of the prostate. More recently, magnetic resonance imaging has been used to measure the membranous urethral length and sphincter volume. Peroperative techniques include preservative and reconstructive approaches. Bladder neck preservation improved early (6 months), as well as long-term (>12 months) continence rates. Several prospective studies have reported earlier return of continence following preservation of puboprostatic ligaments, although no long-term data are available. Preservation of the urethral length yielded controversial outcomes. Concerning postoperative strategies, it is probably optimal to remove the catheter in a window between 4 and 7 days if clinically appropriate; however, more research in this regard is still required. Postoperative PFME (preoperative pelvic floor muscle exercise) appears to speed up the recovery of continence after RP. CONCLUSIONS: Conservative strategies to prevent PPUI include proper patient selection and PFME. Peroperative techniques have largely shown benefit in the short term. Postoperative complications and timing of trial without catheter can influence continence status. Future research initiatives must assess peroperative and postoperative measures, with longer-term follow-up.

Exploring the relation between obesity and urinary incontinence: Pathophysiology, clinical implications, and the effect of weight reduction, ICI-RS 2018.

AIMS: To evaluate the relationship between obesity and urinary incontinence (UI) and to determine the effect of weight reduction on the severity of incontinence. METHODS: This is a consensus report of the proceedings of a Research Proposal from the annual International Consultation on Incontinence-Research Society, 14 June to 16 June, 2018 (Bristol, UK): "What are the relationships between obesity and UI, and the effects of successful bariatric surgery?" RESULTS: Obesity is an increasing problem worldwide and is associated with many adverse effects on health and quality of life. From both translational and clinical studies, there is a strong relationship between obesity and the occurrence of UI. Both mechanical and metabolic factors seem to play an important role including systemic inflammation and oxidative stress due to the release of cytokines in visceral adipose tissue. The success rate of anti-incontinence surgery does not seem to be greatly affected by body mass index (BMI), although reliable data and long-term follow-up are currently lacking. Both weight reduction programs and bariatric surgery can result in amelioration of UI. Various studies have shown that weight loss (particularly that associated with bariatric surgery) can reduce incontinence, and the degree of weight loss is positively correlated with improvement in symptoms. CONCLUSIONS: Obesity is strongly associated with an increased prevalence of both stress and urgency UI. The treatment outcome does not seem to be highly dependent on BMI. Weight reduction is positively correlated with improvement of incontinence symptoms and therefore should be advocated in the management.