A Prospective Multicenter Comparison Study of Risk-adapted Ultrasound-directed and Magnetic Resonance Imaging-directed Diagnostic Pathways for Suspected Prostate Cancer in Biopsy-naïve Men.

BACKGROUND: European Association of Urology guidelines recommend a risk-adjusted biopsy strategy for early detection of prostate cancer in biopsy-naïve men. It remains unclear which strategy is most effective. Therefore, we evaluated two risk assessment pathways commonly used in clinical practice. OBJECTIVE: To compare the diagnostic performance of a risk-based ultrasound (US)-directed pathway (Rotterdam Prostate Cancer Risk Calculator [RPCRC] #3; US volume assessment) and a magnetic resonance imaging (MRI)-directed pathway. DESIGN, SETTING, AND PARTICIPANTS: This was a prospective multicenter study (MR-PROPER) with 1:1 allocation among 21 centers (US arm in 11 centers, MRI arm in ten). Biopsy-naïve men with suspicion of prostate cancer (age ≥50 yr, prostate-specific antigen 3.0-50 ng/ml, ± abnormal digital rectal examination) were included. INTERVENTION: Biopsy-naïve men with elevated risk of prostate cancer, determined using RPCRC#3 in the US arm and Prostate Imaging Reporting and Data System scores of 3-5 in the MRI arm, underwent systematic biopsies (US arm) or targeted biopsies (MRI arm). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was the proportion of men with grade group (GG) ≥2 cancer. Secondary outcomes were the proportions of biopsies avoided and GG 1 cancers detected. Categorical (nonparametric) data were assessed using the Mann-Whitney U test and χ2 tests. RESULTS AND LIMITATIONS: A total of 1965 men were included in the intention-to-treat population (US arm n = 950, MRI arm n = 1015). The US and MRI pathways detected GG ≥2 cancers equally well (235/950, 25% vs 239/1015, 24%; difference 1.2%, 95% confidence interval [CI] -2.6% to 5.0%; p = 0.5). The US pathway detected more GG 1 cancers than the MRI pathway (121/950, 13% vs 84/1015, 8.3%; difference 4.5%, 95% CI 1.8-7.2%; p < 0.01). The US pathway avoided fewer biopsies than the MRI pathway (403/950, 42% vs 559/1015, 55%; difference -13%, 95% CI -17% to -8.3%; p < 0.01). Among men with elevated risk, more GG ≥2 cancers were detected in the MRI group than in the US group (52% vs 43%; difference 9.2%, 95% CI 3.0-15%; p < 0.01). CONCLUSIONS: Risk-adapted US-directed and MRI-directed pathways detected GG ≥2 cancers equally well. The risk-adapted US-directed pathway performs well for prostate cancer diagnosis if prostate MRI capacity and expertise are not available. If prostate MRI availability is sufficient, risk assessment should preferably be performed using MRI, as this avoids more biopsies and detects fewer cases of GG 1 cancer. PATIENT SUMMARY: Among men with suspected prostate cancer, relevant cancers were equally well detected by risk-based pathways using either ultrasound or magnetic resonance imaging (MRI) to guide biopsy of the prostate. If prostate MRI availability is sufficient, risk assessment should be performed with MRI to reduce unnecessary biopsies and detect fewer irrelevant cancers.

Exploratory analysis of the effect of mirabegron on urodynamic sensation parameters and urethral pressure variations.

INTRODUCTION AND HYPOTHESIS: Urethral instability (URI) has in the past been defined by the International Continence Society (ICS), but was excluded from ICS terminology and definitions shortly after because of a lack of consensus about the clinical importance of this phenomenon. Recently, interest in URI and its possible role in overactive bladder (OAB) increased again. In the last decade, a beta 3 adrenoreceptor agonist (mirabegron) was approved for the treatment of OAB. The effect of mirabegron on urethral pressure during filling cystometry is unknown. The aim of this study was to assess the influence of mirabegron on urethral pressure variations during urodynamic investigation and the association of symptoms and voiding diary data before and during treatment. METHODS: This prospective study included 51 consecutive adult female patients, referred with OAB. Patients were evaluated using a voiding diary, two validated questionnaires and two urodynamic investigations, one before and one after 6 weeks of treatment with mirabegron. URI was defined as an urethral pressure drop exceeding 30 cmH2O during filling cystometry. RESULTS: The prevalence of URI was 31% at initial urodynamic investigation, and 19% at second investigation. URI is more common than DO with 18% prevalence at initial evaluation. Treatment with mirabegron resulted in significant changes in symptoms and urodynamic sensory markers in patients with URI. CONCLUSION: Urethral pressure variations are significantly reduced by treatment with mirabegron in patients with URI. URI seems to have a predictive value in treatment choices for OAB. Future research should elucidate this.

Initial report on distribution of ß3-adrenoceptor in the human female urethra.

INTRODUCTION: Past research has demonstrated that the urethral tonus is mainly under sympathetic control. Since 5 years, a beta 3-adrenoceptor (ADRB3) agonist is available in the treatment of overactive bladder syndrome. The presence of ADRB3 within the human urethra has not been demonstrated to date. Presence of ADRB3 in the urethra could influence urethral tonus. The aim of this study is to investigate the presence of ADRB3 in the human female urethra. MATERIAL AND METHODS: We performed anatomical studies in five female specimens. Three specimens were obtained from the body donation program, two from female patients with muscle-invasive bladder cancer, where radical resection of bladder and urethra was performed. The urethra up till the bladder neck was separated from the rest of the bladder and freshly obtained for this study. For demonstrating ADRB3 expression, we used rabbit polyclonal anti-human ADRB3 LS-A4198. RESULTS: Expression of ADBR3 was demonstrated in the epithelial layer of all urethral parts, except at the level of the meatus. The level of ADRB3 expression was highest in the mid urethra. There was no direct contact between ADRB3 and nerve tissue. ADRB3 expression was also demonstrated in the stratified muscle layer at the level of the external urethral sphincter. CONCLUSIONS: This is the first study to demonstrate the expression of ADRB3 in the human female urethra. There is an absence of a direct connection between ADRB3 and nerve tissue.

Continuous urethral pressure measurements; measurement techniques; pressure variations; clinical interpretations; and clinical relevance. A Systematic Literature Analysis.

AIMS: The clinical relevance of urethral pressure variations (UPV) in the pathophysiology of over active bladder syndrome (OAB) has remained controversial to date. Some studies report an association with OAB and/or detrusor over activity (DO). Recently the International Consultation on Incontinence-Research Society recommended new clinical research to be performed on this subject. We provide a systematic review of the literature to specify this recommendation. METHODS: Literature search was performed in PubMed, Embase, Web of Science, Cochrane, Central, Cinahl, Academic Science Premier, Science Direct, and Wiley Online using a sensitive search string combination. All authors independently reviewed and scored full text papers and consensus about methodological quality was obtained according to Oxford Level of Evidence (LoE). RESULTS: Four hundred eighty seven abstracts were screened, 25 papers met all predefined inclusion selection criteria. Incidence figures of UPV varied between 2% and 95%. Studies are of poor methodological quality with Oxford LoE scores of 3B and 4. Measurement methods and techniques show a large variety. The above mentioned association of DO/OAB with UPV is however frequently reported. CONCLUSION: There exists a phenomenon of UPV, apart from DO, which may be a separate entity within OAB syndrome. Large variation in measurement techniques and patient populations hinders fundamental research as well as clinical progress. Clinical relevance of UPV and consequences for treatment therefore are yet to be established. Future prospective research with well-defined patient population and standardised urodynamic measurement techniques is needed. Results of standardized and objective evaluations should be compared to clinical signs and symptoms by validated questionnaires. Neurourol. Urodynam. 36:51-56, 2017. © 2015 Wiley Periodicals, Inc.

Urodynamic evaluation of sacral neuromodulation for urge urinary incontinence.

OBJECTIVE: To evaluate the urodynamic data before and 6 months after implantation of sacral neuromodulation (SNM, an established treatment for voiding dysfunction, including refractory urge urinary incontinence, UI) and to assess the correlation between the urodynamic data and clinical efficacy in patients with UI. PATIENTS AND METHODS: In all, 111 patients with a >50% reduction in UI symptoms during a percutaneous nerve evaluation test qualified for surgical implantation of SNM. Patients were categorized in two subgroups, i.e. those with UI with or without confirmed detrusor overactivity (DO) at baseline. At the 6-month follow-up all patients had a second urodynamic investigation, with the stimulator switched on. RESULTS: At baseline, there was urodynamically confirmed DO in 67 patients, while 44 showed no DO. A review of filling cystometry variables showed a statistically significant improvement in bladder volumes at first sensation of filling (FSF) and at maximum fill volume (MFV) before voiding for both UI subgroups, compared with baseline. In 51% of the patients with UI and DO at baseline, the DO resolved during the follow-up. However, those patients were no more clinically successful than those who still had DO (P = 0.73). At the 6-month follow-up, 55 of 84 implanted patients showed clinical benefit, having a >or=50% improvement in primary voiding diary variables. Patients with UI but no DO had a higher rate of clinical success (73%) than patients with UI and DO (61%), but the difference was not statistically significant. CONCLUSION: These urodynamic results show a statistically significant improvement in FSF and MFV in patients with UI with or with no DO after SNM. Although there was a urodynamic and clinical improvement in both groups, patients with UI but no DO are at least as successful as patients with UI and DO. Therefore in patients with UI, DO should not be a prerequisite selection criterion for using SNM.

Five-Year Follow-up After Sacral Neuromodulation: Single Center Experience.

Objective. We studied long-term clinical efficacy of sacral neuromodulation (SNM) therapy in patients with refractory urgency incontinence (UI), urgency/frequency (UF) and voiding difficulty (VD), together with urodynamic data at baseline and six months postimplant. Materials and Methods. Twenty-two patients were implanted with a neurostimulator after a positive response to a percutaneous nerve evaluation test defined as a greater than 50% improvement in symptoms. Results. At five-year follow-up, the number of incontinent episodes and pad usage per day decreased significantly in 10 out of 15 UI patients. Two of five UF patients were successfully treated with SNM; the number of daily voids for all UF patients decreased from 25 to 19 and average voided volume increased from 98 to 212 mL. One of the two VD patients was able to void to completion. Mean first sensation of filling at the six-month urodynamic investigation for the UI and UF patients increased from 78 to 241 mL and 141 to 232 mL, respectively, and the maximum bladder capacity increased from 292 to 352 mL and 223 to 318 mL, respectively. Five of 22 patients underwent device explant and one patient still has an inactive stimulator implanted. Conclusion. SNM is an effective treatment modality that offers sustained clinical benefit in the majority of patients with refractory UI, UF, and VD that do not respond to other, more conservative therapies.