Tobias Gross

EAU–ESTRO–SIOG Guidelines on Prostate Cancer. Part 1: Screening, Diagnosis, and Local Treatment with Curative Intent

OBJECTIVE To present a summary of the 2016 version of the European Association of Urology (EAU) - European Society for Radiotherapy & Oncology (ESTRO) - International Society of Geriatric Oncology (SIOG) Guidelines on screening, diagnosis, and local treatment with curative intent of clinically localised prostate cancer (PCa). EVIDENCE ACQUISITION The working panel performed a literature review of the new data (2013-2015). The guidelines were updated and the levels of evidence and/or grades of recommendation were added based on a systematic review of the evidence. EVIDENCE SYNTHESIS BRCA2 mutations have been added as risk factors for early and aggressive disease. In addition to the Gleason score, the five-tier 2014 International Society of Urological Pathology grading system should now be provided. Systematic screening is still not recommended. Instead, an individual risk-adapted strategy following a detailed discussion and taking into account the patients wishes and life expectancy must be considered. An early prostate-specific antigen test, the use of a risk calculator, or one of the promising biomarker tools are being investigated and might be able to limit the overdetection of insignificant PCa. Breaking the link between diagnosis and treatment may lower the overtreatment risk. Multiparametric magnetic resonance imaging using standardised reporting cannot replace systematic biopsy, but robustly nested within the diagnostic work-up, it has a key role in local staging. Active surveillance always needs to be discussed with very low-risk patients. The place of surgery in high-risk disease and the role of lymph node dissection have been clarified, as well as the management of node-positive patients. Radiation therapy using dose-escalated intensity-modulated technology is a key treatment modality with recent improvement in the outcome based on increased doses as well as combination with hormonal treatment. Moderate hypofractionation is safe and effective, but longer-term data are still lacking. Brachytherapy represents an effective way to increase the delivered dose. Focal therapy remains experimental while cryosurgery and HIFU are still lacking long-term convincing results. CONCLUSIONS The knowledge in the field of diagnosis, staging, and treatment of localised PCa is evolving rapidly. The 2016 EAU-ESTRO-SIOG Guidelines on PCa summarise the most recent findings and advice for the use in clinical practice. These are the first PCa guidelines endorsed by the European Society for Radiotherapy and Oncology and the International Society of Geriatric Oncology and reflect the multidisciplinary nature of PCa management. A full version is available from the EAU office and online (http://uroweb.org/guideline/prostate-cancer/). PATIENT SUMMARY The 2016 EAU-STRO-IOG Prostate Cancer (PCa) Guidelines present updated information on the diagnosis, and treatment of clinically localised prostate cancer. In Northern and Western Europe, the number of men diagnosed with PCa has been on the rise. This may be due to an increase in opportunistic screening, but other factors may also be involved (eg, diet, sexual behaviour, low exposure to ultraviolet radiation). We propose that men who are potential candidates for screening should be engaged in a discussion with their clinician (also involving their families and caregivers) so that an informed decision may be made as part of an individualised risk-adapted approach.

Summary of European Association of Urology (EAU) Guidelines on Neuro-Urology

CONTEXT Most patients with neuro-urological disorders require life-long medical care. The European Association of Urology (EAU) regularly updates guidelines for the diagnosis and treatment of these patients. OBJECTIVE To provide a summary of the 2015 updated EAU Guidelines on Neuro-Urology. EVIDENCE ACQUISITION Structured literature searches in several databases were carried out to update the 2014 guidelines. Levels of evidence and grades of recommendation were assigned where possible. EVIDENCE SYNTHESIS Neurological disorders often cause urinary tract, sexual, and bowel dysfunction. Most neuro-urological patients need life-long care for optimal life expectancy and quality of life. Timely diagnosis and treatment are essential to prevent upper and lower urinary tract deterioration. Clinical assessment should be comprehensive and usually includes a urodynamic investigation. The neuro-urological management must be tailored to the needs of the individual patient and may require a multidisciplinary approach. Sexuality and fertility issues should not be ignored. Numerous conservative and noninvasive possibilities of management are available and should be considered before a surgical approach is chosen. Neuro-urological patients require life-long follow-up and particular attention has to be paid to this aspect of management. CONCLUSIONS The current EAU Guidelines on Neuro-Urology provide an up-to-date overview of the available evidence for adequate diagnosis, treatment, and follow-up of neuro-urological patients. PATIENT SUMMARY Patients with a neurological disorder often suffer from urinary tract, sexual, and bowel dysfunction and life-long care is usually necessary. The update of the EAU Guidelines on Neuro-Urology, summarized in this paper, enables caregivers to provide optimal support to neuro-urological patients. Conservative, noninvasive, or minimally invasive approaches are often possible.

What Is the Negative Predictive Value of Multiparametric Magnetic Resonance Imaging in Excluding Prostate Cancer at Biopsy? A Systematic Review and Meta-analysis from the European Association of Urology Prostate Cancer Guidelines Panel

CONTEXT It remains unclear whether patients with a suspicion of prostate cancer (PCa) and negative multiparametric magnetic resonance imaging (mpMRI) can safely obviate prostate biopsy. OBJECTIVE To systematically review the literature assessing the negative predictive value (NPV) of mpMRI in patients with a suspicion of PCa. EVIDENCE ACQUISITION The Embase, Medline, and Cochrane databases were searched up to February 2016. Studies reporting prebiopsy mpMRI results using transrectal or transperineal biopsy as a reference standard were included. We further selected for meta-analysis studies with at least 10-core biopsies as the reference standard, mpMRI comprising at least T2-weighted and diffusion-weighted imaging, positive mpMRI defined as a Prostate Imaging Reporting Data System/Likert score of ≥3/5 or ≥4/5, and results reported at patient level for the detection of overall PCa or clinically significant PCa (csPCa) defined as Gleason ≥7 cancer. EVIDENCE SYNTHESIS A total of 48 studies (9613 patients) were eligible for inclusion. At patient level, the median prevalence was 50.4% (interquartile range [IQR], 36.4-57.7%) for overall cancer and 32.9% (IQR, 28.1-37.2%) for csPCa. The median mpMRI NPV was 82.4% (IQR, 69.0-92.4%) for overall cancer and 88.1% (IQR, 85.7-92.3) for csPCa. NPV significantly decreased when cancer prevalence increased, for overall cancer (r=-0.64, p<0.0001) and csPCa (r=-0.75, p=0.032). Eight studies fulfilled the inclusion criteria for meta-analysis. Seven reported results for overall PCa. When the overall PCa prevalence increased from 30% to 60%, the combined NPV estimates decreased from 88% (95% confidence interval [95% CI], 77-99%) to 67% (95% CI, 56-79%) for a cut-off score of 3/5. Only one study selected for meta-analysis reported results for Gleason ≥7 cancers, with a positive biopsy rate of 29.3%. The corresponding NPV for a cut-off score of ≥3/5 was 87.9%. CONCLUSIONS The NPV of mpMRI varied greatly depending on study design, cancer prevalence, and definitions of positive mpMRI and csPCa. As cancer prevalence was highly variable among series, risk stratification of patients should be the initial step before considering prebiopsy mpMRI and defining those in whom biopsy may be omitted when the mpMRI is negative. PATIENT SUMMARY This systematic review examined if multiparametric magnetic resonance imaging (MRI) scan can be used to reliably predict the absence of prostate cancer in patients suspected of having prostate cancer, thereby avoiding a prostate biopsy. The results suggest that whilst it is a promising tool, it is not accurate enough to replace prostate biopsy in such patients, mainly because its accuracy is variable and influenced by the prostate cancer risk. However, its performance can be enhanced if there were more accurate ways of determining the risk of having prostate cancer. When such tools are available, it should be possible to use an MRI scan to avoid biopsy in patients at a low risk of prostate cancer.

Tibial Nerve Stimulation for Treating Neurogenic Lower Urinary Tract Dysfunction: A Systematic Review.

CONTEXT Tibial nerve stimulation (TNS) is a promising therapy for non-neurogenic lower urinary tract dysfunction and might also be a valuable option for patients with an underlying neurological disorder. OBJECTIVE We systematically reviewed all available evidence on the efficacy and safety of TNS for treating neurogenic lower urinary tract dysfunction (NLUTD). EVIDENCE ACQUISITION The review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement. EVIDENCE SYNTHESIS After screening 1943 articles, 16 studies (4 randomized controlled trials [RCTs], 9 prospective cohort studies, 2 retrospective case series, and 1 case report) enrolling 469 patients (283 women and 186 men) were included. Five studies reported on acute TNS and 11 on chronic TNS. In acute and chronic TNS, the mean increase of maximum cystometric capacity ranged from 56 to 132mL and from 49 to 150mL, and the mean increase of bladder volume at first detrusor overactivity ranged from 44 to 92mL and from 93 to 121mL, respectively. In acute and chronic TNS, the mean decrease of maximum detrusor pressure during the storage phase ranged from 5 to 15cm H2O and from 4 to 21cm H2O, respectively. In chronic TNS, the mean decrease in number of voids per 24h, in number of leakages per 24h, and in postvoid residual ranged from 3 to 7, from 1 to 4, and from 15 to 55mL, respectively. No TNS-related adverse events have been reported. Risk of bias and confounding was high in most studies. CONCLUSIONS Although preliminary data of RCTs and non-RCTs suggest TNS might be effective and safe for treating NLUTD, the evidence base is poor, derived from small, mostly noncomparative studies with a high risk of bias and confounding. More reliable data from well-designed RCTs are needed to reach definitive conclusions. PATIENT SUMMARY Early data suggest tibial nerve stimulation might be effective and safe for treating neurogenic lower urinary tract dysfunction, but more reliable evidence is required.

Orthotopic Ileal Bladder Substitution in Women: Factors Influencing Urinary Incontinence and Hypercontinence ☆

BACKGROUND Urinary incontinence or the inability to void spontaneously after ileal orthotopic bladder substitution is a frequent finding in female patients. OBJECTIVE To evaluate how hysterectomy and nerve sparing affect functional outcomes and whether these relate to pre- and postoperative urethral pressure profile (UPP) results. DESIGN, SETTING, AND PARTICIPANTS Prospectively performed pre- and postoperative UPPs of 73 female patients who had undergone cystectomy and bladder substitution were correlated with postoperative voiding and continence status. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Outcome analyses were performed with the Kruskal-Wallis test, Wilcoxon-Mann-Whitney, or two-group post hoc testing with the Bonferroni correction. Chi-square or Fisher exact tests were applied for the categorical data. RESULTS AND LIMITATIONS Of postoperatively continent or hypercontinent patients, 22 of 43 (51.2%) had the uterus preserved; of incontinent patients, only 4 of 30 (13.3%, p<0.01) had the uterus preserved. Of postoperatively continent or hypercontinent patients, 27 of 43 patients (62.8%) had bilateral and 15 of 43 (34.9%) had unilateral attempted nerve sparing. In incontinent patients, 11 of 30 (36.7%) had bilateral and 16 of 30 (53.3%) had unilateral attempted nerve sparing (p=0.02). When compared with postoperatively incontinent patients, postoperatively continent patients had a longer functional urethral length (median: 32mm vs 24mm; p<0.001), a higher postoperative urethral closing pressure at rest (56cm H2O vs 35cm H2O; p<0.001) as well as a higher preoperative urethral closing pressure at rest (74cm H2O vs 47.5cm H2O; p=0.01). The main limitation was the limited number of patients. CONCLUSIONS In female patients undergoing radical cystectomy and bladder substitution, preservation of the uterus and attempted nerve sparing results in better functional outcomes. The preoperative UPPs correlate with postoperative voiding and continence status and may predict which patients are at a higher risk of functional failure after bladder substitution. PATIENT SUMMARY If preservation of the urethras innervation is not possible during cystectomy, poor functional results with bladder substitutes are likely.

Transcutaneous Electrical Nerve Stimulation for Treating Neurogenic Lower Urinary Tract Dysfunction: A Systematic Review

CONTEXT Transcutaneous electrical nerve stimulation (TENS) is a promising therapy for non-neurogenic lower urinary tract dysfunction and might also be a valuable option in patients with an underlying neurological disorder. OBJECTIVE We systematically reviewed all available evidence on the efficacy and safety of TENS for treating neurogenic lower urinary tract dysfunction. EVIDENCE ACQUISITION The review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement. EVIDENCE SYNTHESIS After screening 1943 articles, 22 studies (two randomised controlled trials, 14 prospective cohort studies, five retrospective case series, and one case report) enrolling 450 patients were included. Eleven studies reported on acute TENS and 11 on chronic TENS. In acute TENS and chronic TENS, the mean increase of maximum cystometric capacity ranged from 69ml to 163ml and from 4ml to 156ml, the mean change of bladder volume at first detrusor overactivity from a decrease of 13ml to an increase of 175ml and from an increase of 10ml to 120ml, a mean decrease of maximum detrusor pressure at first detrusor overactivity from 18 cmH20 to 72 cmH20 and 8 cmH20, and a mean decrease of maximum storage detrusor pressure from 20 cmH20 to 58 cmH2O and from 3 cmH20 to 8 cmH2O, respectively. In chronic TENS, a mean decrease in the number of voids and leakages per 24h ranged from 1 to 3 and from 0 to 4, a mean increase of maximum flow rate from 2ml/s to 7ml/s, and a mean change of postvoid residual from an increase of 26ml to a decrease of 85ml. No TENS-related serious adverse events have been reported. Risk of bias and confounding was high in most studies. CONCLUSIONS Although preliminary data suggest TENS might be effective and safe for treating neurogenic lower urinary tract dysfunction, the evidence base is poor and more reliable data from well-designed randomised controlled trials are needed to make definitive conclusions. PATIENT SUMMARY Early data suggest that transcutaneous electrical nerve stimulation might be effective and safe for treating neurogenic lower urinary tract dysfunction, but more reliable evidence is required.

Long-term effectiveness and complication rates of bladder augmentation in patients with neurogenic bladder dysfunction: A systematic review

To systematically evaluate effectiveness and safety of bladder augmentation for adult neuro‐urological patients.

Value of urodynamic findings in predicting upper urinary tract damage in neuro-urological patients: A systematic review

The main goals of neurogenic lower urinary tract dysfunction (NLUTD) management are preventing upper urinary tract damage (UUTD), improving continence, and quality of life. Here, we aimed to systematically assess all available evidence on urodynamics predicting UUTD in patients with NLUTD.

A Quality Assessment of Patient-Reported Outcome Measures for Sexual Function in Neurologic Patients Using the Consensus-based Standards for the Selection of Health Measurement Instruments Checklist: A Systematic Review

CONTEXT Impaired sexual function has a significant effect on quality of life. Various patient-reported outcome measures (PROMs) are available to evaluate sexual function. The quality of the PROMs to be used for neurologic patients remains unknown. OBJECTIVE To systematically review which validated PROMs are available to evaluate sexual function in neurologic patients and to critically assess the quality of the validation studies and measurement properties for each identified PROM. EVIDENCE ACQUISITION A systematic review was performed according to the Preferred Reporting Items for Systematic Review and Meta-analysis statement. The included publications were assessed according to the Consensus-Based Standards for the Selection of Health Measurement Instruments checklist. EVIDENCE SYNTHESIS Twenty-one studies for PROMs regarding sexual function were identified for the following patient groups: spinal cord injury (11 studies), multiple sclerosis (MS; 6 studies), Parkinsons disease (2 studies), traumatic brain injury (1 study), and epilepsy (1 study). The evidence for the quality of PROMs was found to be variable, and overall evaluation of measurement properties was lacking in 71% of the studies. The measurement error and responsiveness were not studied in any of the publications. CONCLUSIONS Several PROMs have been identified to evaluate sexual function in neurologic patients. Strong evidence was found only for the Multiple Sclerosis Intimacy and Sexuality Questionnaire-15 and Multiple Sclerosis Intimacy and Sexuality Questionnaire-19 for patients with MS, although evidence was lacking for certain measurement properties as well. Future research should focus on identifying relevant PROMs and establishing adequate quality for all measurement properties in studies with high methodological quality. PATIENT SUMMARY A quality assessment of patient-reported outcome measures (PROMs) for sexual function in neurologic patients was made. The evidence found for good PROMs was limited. Studies with high methodological quality are needed to improve the quality of PROMs to evaluate sexual function in neurologic patients.

Continent catheterizable tubes/stomas in adult neuro‐urological patients: A systematic review

To systematically review all available evidence on the effectiveness and complications of continent cutaneous stoma or tube (CCS/T) to treat bladder‐emptying difficulties in adult neuro‐urological patients.