A Systematic Review of the Efficacy and Toxicity of Brachytherapy Boost Combined with External Beam Radiotherapy for Nonmetastatic Prostate Cancer.

CONTEXT: The optimum use of brachytherapy (BT) combined with external beam radiotherapy (EBRT) for localised/locally advanced prostate cancer (PCa) remains uncertain. OBJECTIVE: To perform a systematic review to determine the benefits and harms of EBRT-BT. EVIDENCE ACQUISITION: Ovid MEDLINE, Embase, and EBM Reviews-Cochrane Central Register of Controlled Trials databases were systematically searched for studies published between January 1, 2000 and June 7, 2022, according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. Eligible studies compared low- or high-dose-rate EBRT-BT against EBRT ± androgen deprivation therapy (ADT) and/or radical prostatectomy (RP) ± postoperative radiotherapy (RP ± EBRT). The main outcomes were biochemical progression-free survival (bPFS), severe late genitourinary (GU)/gastrointestinal toxicity, metastasis-free survival (MFS), cancer-specific survival (CSS), and overall survival (OS), at/beyond 5 yr. Risk of bias was assessed and confounding assessment was performed. A meta-analysis was performed for randomised controlled trials (RCTs). EVIDENCE SYNTHESIS: Seventy-three studies were included (two RCTs, seven prospective studies, and 64 retrospective studies). Most studies included participants with intermediate-or high-risk PCa. Most studies, including both RCTs, used ADT with EBRT-BT. Generally, EBRT-BT was associated with improved bPFS compared with EBRT, but similar MFS, CSS, and OS. A meta-analysis of the two RCTs showed superior bPFS with EBRT-BT (estimated fixed-effect hazard ratio [HR] 0.54 [95% confidence interval {CI} 0.40-0.72], p < 0.001), with absolute improvements in bPFS at 5-6 yr of 4.9-16%. However, no difference was seen for MFS (HR 0.84 [95% CI 0.53-1.28], p = 0.4) or OS (HR 0.87 [95% CI 0.63-1.19], p = 0.4). Fewer studies examined RP ± EBRT. There is an increased risk of severe late GU toxicity, especially with low-dose-rate EBRT-BT, with some evidence of increased prevalence of severe GU toxicity at 5-6 yr of 6.4-7% across the two RCTs. CONCLUSIONS: EBRT-BT can be considered for unfavourable intermediate/high-risk localised/locally advanced PCa in patients with good urinary function, although the strength of this recommendation based on the European Association of Urology guideline methodology is weak given that it is based on improvements in biochemical control. PATIENT SUMMARY: We found good evidence that radiotherapy combined with brachytherapy keeps prostate cancer controlled for longer, but it could lead to worse urinary side effects than radiotherapy without brachytherapy, and its impact on cancer spread and patient survival is less clear.

Outcomes of Flexible Ureteroscopy vs Extracorporeal Shock Wave Lithotripsy for Renal Stones in Pediatric Patients: A European Association of Urology Urolithiasis Guidelines Systematic Review and Meta-Analysis.

PURPOSE: We sought to determine which treatment between flexible ureteroscopy and shock wave lithotripsy has a better stone-free rate in pediatric patients (<18 years) with renal or proximal ureteric stones (<2 cm). Subanalysis for all outcomes for randomized controlled trials only. MATERIALS AND METHODS: Using PubMed, Web of Science, and the Cochrane database, we identified studies (randomized clinical trials and prospective comparative nonrandomized studies) published until August 2022 reporting surgical outcomes of pediatrics patients undergoing flexible ureteroscopy and shock wave lithotripsy with renal or proximal ureteric stones <2 cm (PROSPERO ID: CRD42022378790). Only randomized controlled trials were considered for meta-analysis. Stone-free rate, operative time, and complications were analyzed. Analysis was performed in R. RESULTS: A total of 6 studies identified, of which 3 were randomized clinical trials and 4 had data on renal stones. A total of 669 patients were analyzed. Mean age ranged from 4.4 to 12.4 years. The shock wave lithotripsy group presented a range of stone-free rate between 21 and 90% while the flexible ureteroscopy group presented a range of stone-free rates between 37% and 97%. Meta-analysis of randomized controlled trials only (n=302) demonstrated significantly higher stone-free rate in flexible ureteroscopy vs shock wave lithotripsy (RR = 1.17, 95% CI: 1.04-1.33, P = 0.01), operative time (mean difference = +16.4 minutes, 95% CI: 7.3-25.5, P < 0.01) and hospital stay (mean difference = +0.25 days, 95% CI: 0.14-0.36, P < 0.001). But no difference in fluoroscopy exposure time (mean difference = -21.0 seconds, 95% CI: -42.6 to 0.56, P = 0.07), Clavien I-II (RR = 1.23, 95% CI: 0.71-2.12, P = 0.45) or Clavien III-V complications (RR = 1.04, 95% CI: 0.32-3.42, P = 0.95). CONCLUSIONS: Flexible ureteroscopy has a significantly higher stone-free rate than shock wave lithotripsy, with no difference in complication rate or fluoroscopy exposure time, and significantly higher operative times and hospital stay. However, the current evidence base for this is weak and further randomized trials are needed.

Comparison of Treatment Outcomes for Fluoroscopic and Fluoroscopy-free Endourological Procedures: A Systematic Review on Behalf of the European Association of Urology Urolithiasis Guidelines Panel.

CONTEXT: Endourological procedures frequently require fluoroscopic guidance, which results in harmful radiation exposure to patients and staff. One clinician-controlled method for decreasing exposure to ionising radiation in patients with urolithiasis is to avoid the use of intraoperative fluoroscopy during stone intervention procedures. OBJECTIVE: To comparatively assess the benefits and risks of "fluoroscopy-free" and fluoroscopic endourological interventions in patients with urolithiasis. EVIDENCE ACQUISITION: A systematic review of the literature from 1970 to 2022 was performed using the MEDLINE/PubMed, Embase, and Cochrane controlled trials databases and ClinicalTrials.gov. Primary outcomes assessed were complications and the stone-free rate (SFR). Studies reporting data on ureteroscopy and percutaneous nephrolithotomy (PCNL) were eligible for inclusion. Secondary outcomes were operative duration, hospital length of stay, conversion from a fluoroscopy-free to a fluoroscopic procedure, and requirement for an auxiliary procedure to achieve stone clearance. EVIDENCE SYNTHESIS: In total, 24 studies (12 randomised and 12 observational) out of 834 abstracts screened were eligible for analysis. There were 4564 patients with urolithiasis in total, of whom 2309 underwent a fluoroscopy-free procedure and 2255 underwent a comparative fluoroscopic procedure for treatment of urolithiasis. Pooled analysis of all procedures revealed no significant difference between the groups in SFR (p = 0.84), operative duration (p = 0.11), or length of stay (p = 0.13). Complication rates were significantly higher in the fluoroscopy group (p = 0.009). The incidence of conversion from a fluoroscopy-free to a fluoroscopic procedure was 2.84%. Similar results were noted in subanalyses for ureteroscopy (n = 2647) and PCNL (n = 1917). When only randomised studies were analysed (n = 12), the overall complication rate was significantly in the fluoroscopy group (p < 0.001). CONCLUSIONS: For carefully selected patients with urolithiasis, fluoroscopy-free and fluoroscopic endourological procedures have comparable stone-free and complication rates when performed by experienced urologists. In addition, the conversion rate from a fluoroscopy-free to a fluoroscopic endourological procedure is low at 2.84%. These findings are important for clinicians and patients, as the detrimental health effects of ionising radiation are negated with fluoroscopy-free procedures. PATIENT SUMMARY: We compared treatments for kidney stones with and without the use of radiation. We found that kidney stone procedures without the use of radiation can be safely performed by experienced urologists in patients with normal kidney anatomy. These findings are important, as they indicate that the harmful effects of radiation can be avoided during kidney stone surgery.

Evaluation of the Effectiveness of Interventions on Nephrolithiasis in Transplanted Kidney.

CONTEXT: De Novo nephrolithiasis in renal transplant can have severe consequences since renal transplantation involves a single functioning kidney with medical and anatomical specificities (heterotopic transplantation on iliac vessels, immunosuppressive treatments, and comorbidities). OBJECTIVE: To systematically review all available evidence on the prevalence of de novo nephrolithiasis in renal transplant, presentation, and stone characteristics, and to report in a meta-analysis the efficacy of stone treatments (extracorporeal shock wave lithotripsy [ESWL], medical treatment, percutaneous nephrolithotomy [PCNL], open surgery, and ureteroscopy). EVIDENCE ACQUISITION: Medline, Embase, and the Cochrane Library were searched up to November 2021 for all relevant publications reporting the management of de novo nephrolithiasis in renal allografts. The primary outcome was stone-free rate (SFR) at 3 mo. Secondary outcomes included prevalence, stone characteristics (size, density, and composition), symptoms on presentation, need for drainage, complications, and recurrence. Data were narratively synthesized in light of methodological and clinical heterogeneity, and a meta-analysis was performed for SFR. The risk of bias of each included study was assessed. EVIDENCE SYNTHESIS: We included 37 retrospective studies with 553 patients and 612 procedures; of the 612 procedures 20 were antegrade ureteroscopy, 154 retrograde ureteroscopy, 118 PCNL, 25 open surgery, 155 ESWL, and 140 surveillance/medical treatment. The prevalence of nephrolithiasis in renal transplant was 1.0%. The mean stone size on diagnosis was 11 mm (2-50). The overall SFR at 3 mo was 82%: 96% with open surgery, 95% with antegrade ureteroscopy, 86% with PCNL, 81% with retrograde ureteroscopy, and 75% with ESWL. CONCLUSIONS: De novo nephrolithiasis in renal transplant is an infrequent condition. A high SFR were obtained with an antegrade approach (ureteroscopy, PCNL, and open approach) that should be considered in renal transplant patients owing to the heterotopic position of the renal graft. The choice of technique was correlated with stone size: generally ureteroscopy and ESWL for stones 11-12 mm (mean stone size) versus PCNL and open surgery for 17-25 mm stones. PATIENT SUMMARY: De novo nephrolithiasis in renal transplants is an infrequent situation that can have severe consequences on the function of the renal graft. We evaluated the efficacy of each treatment and noted that antegrade approaches (open surgery, percutaneous nephrolithotomy, and antegrade ureteroscopy) were associated with the highest stone-free rate. As opposed to the management of nephrolithiasis in native kidney, an antegrade approach should be considered more in renal transplant patients.

Best Practice in Interventional Management of Urolithiasis: An Update from the European Association of Urology Guidelines Panel for Urolithiasis 2022.

PURPOSE: The European Association of Urology (EAU) has updated its guidelines on clinical best practice in urolithiasis for 2021. We therefore aimed to present a summary of best clinical practice in surgical intervention for patients with upper tract urolithiasis. MATERIALS AND METHODS: The panel performed a comprehensive literature review of novel data up to May 2021. The guidelines were updated and a strength rating was given for each recommendation, graded using the modified Grading of Recommendations, Assessment, Development, and Evaluations methodology. RESULTS: The choice of surgical intervention depends on stone characteristics, patient anatomy, comorbidities, and choice. For shockwave lithotripsy (SWL), the optimal shock frequency is 1.0-1.5 Hz. For ureteroscopy (URS), a postoperative stent is not needed in uncomplicated cases. Flexible URS is an alternative if percutaneous nephrolithotomy (PCNL) or SWL is contraindicated, even for stones >2 cm. For PCNL, prone and supine approaches are equally safe. For uncomplicated PCNL cases, a nephrostomy tube after PCNL is not necessary. Radiation exposure for endourological procedures should follow the as low as reasonably achievable principles. CONCLUSIONS: This is a summary of the EAU urolithiasis guidelines on best clinical practice in interventional management of urolithiasis. The full guideline is available at https://uroweb.org/guidelines/urolithiasis. PATIENT SUMMARY: The European Association of Urology has produced guidelines on the best management of kidney stones, which are summarised in this paper. Kidney stone disease is a common condition; computed tomography (CT) is increasingly used to diagnose it. The guidelines aim to decrease radiation exposure to patients by minimising the use of x-rays and CT scans. We detail specific advice around the common operations for kidney stones.

Radiological features characterising indeterminate testes masses: a systematic review and meta-analysis.

CONTEXT: The use of scrotal ultrasonography (SUS) has increased the detection rate of indeterminate testicular masses. Defining radiological characteristics that identify malignancy may reduce the number of men undergoing unnecessary radical orchidectomy. OBJECTIVE: To define which SUS or scrotal magnetic resonance imaging (MRI) characteristics can predict benign or malignant disease in pre- or post-pubertal males with indeterminate testicular masses. EVIDENCE ACQUISITION: This systematic review was conducted in accordance with Cochrane Collaboration guidance. Medline, Embase, Cochrane controlled trials and systematic reviews databases were searched from (1970 to 26 March 2021). Benign and malignant masses were classified using the reported reference test: i.e., histopathology, or 12 months progression-free radiological surveillance. Risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 tool (QUADAS-2). EVIDENCE SYNTHESIS: A total of 32 studies were identified, including 1692 masses of which 28 studies and 1550 masses reported SUS features, four studies and 142 masses reported MRI features. Meta-analysis of different SUS (B-mode) values in post-pubertal men demonstrated that a size of ≤0.5 cm had a significantly lower odds ratio (OR) of malignancy compared to masses of >0.5 cm (P < 0.001). Comparison of masses of 0.6-1.0 cm and masses of >1.5 cm also demonstrated a significantly lower OR of malignancy (P = 0.04). There was no significant difference between masses of 0.6-1.0 and 1.1-1.5 cm. SUS in post-pubertal men also had a statistically significantly lower OR of malignancy for heterogenous masses vs homogenous masses (P = 0.04), hyperechogenic vs hypoechogenic masses (P < 0.01), normal vs increased enhancement (P < 0.01), and peripheral vs central vascularity (P < 0.01), respectively. There were limited data on pre-pubertal SUS, pre-pubertal MRI and post-pubertal MRI. CONCLUSIONS: This meta-analysis identifies radiological characteristics that have a lower OR of malignancy and may be of value in the management of the indeterminate testis mass.

Systematic Review of Active Surveillance for Clinically Localised Prostate Cancer to Develop Recommendations Regarding Inclusion of Intermediate-risk Disease, Biopsy Characteristics at Inclusion and Monitoring, and Surveillance Repeat Biopsy Strategy.

CONTEXT: There is uncertainty regarding the most appropriate criteria for recruitment, monitoring, and reclassification in active surveillance (AS) protocols for localised prostate cancer (PCa). OBJECTIVE: To perform a qualitative systematic review (SR) to issue recommendations regarding inclusion of intermediate-risk disease, biopsy characteristics at inclusion and monitoring, and repeat biopsy strategy. EVIDENCE ACQUISITION: A protocol-driven, Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA)-adhering SR incorporating AS protocols published from January 1990 to October 2020 was performed. The main outcomes were criteria for inclusion of intermediate-risk disease, monitoring, reclassification, and repeat biopsy strategies (per protocol and/or triggered). Clinical effectiveness data were not assessed. EVIDENCE SYNTHESIS: Of the 17 011 articles identified, 333 studies incorporating 375 AS protocols, recruiting 264 852 patients, were included. Only a minority of protocols included the use of magnetic resonance imaging (MRI) for recruitment (n = 17), follow-up (n = 47), and reclassification (n = 26). More than 50% of protocols included patients with intermediate or high-risk disease, whilst 44.1% of protocols excluded low-risk patients with more than three positive cores, and 39% of protocols excluded patients with core involvement (CI) >50% per core. Of the protocols, ≥80% mandated a confirmatory transrectal ultrasound biopsy; 72% (n = 189) of protocols mandated per-protocol repeat biopsies, with 20% performing this annually and 25% every 2 yr. Only 27 protocols (10.3%) mandated triggered biopsies, with 74% of these protocols defining progression or changes on MRI as triggers for repeat biopsy. CONCLUSIONS: For AS protocols in which the use of MRI is not mandatory or absent, we recommend the following: (1) AS can be considered in patients with low-volume International Society of Urological Pathology (ISUP) grade 2 (three or fewer positive cores and cancer involvement ≤50% CI per core) or another single element of intermediate-risk disease, and patients with ISUP 3 should be excluded; (2) per-protocol confirmatory prostate biopsies should be performed within 2 yr, and per-protocol surveillance repeat biopsies should be performed at least once every 3 yr for the first 10 yr; and (3) for patients with low-volume, low-risk disease at recruitment, if repeat systematic biopsies reveal more than three positive cores or maximum CI >50% per core, they should be monitored closely for evidence of adverse features (eg, upgrading); patients with ISUP 2 disease with increased core positivity and/or CI to similar thresholds should be reclassified. PATIENT SUMMARY: We examined the literature to issue new recommendations on active surveillance (AS) for managing localised prostate cancer. The recommendations include setting criteria for including men with more aggressive disease (intermediate-risk disease), setting thresholds for close monitoring of men with low-risk but more extensive disease, and determining when to perform repeat biopsies (within 2 yr and 3 yearly thereafter).

A Systematic Review of the Efficacy and Safety of Outpatient Bladder Tumour Ablation.

CONTEXT: Management of non-muscle-invasive bladder cancer (NMIBC) is costly and associated with negative health-related quality-of-life effects, in part because of the frequent need for repeated transurethral resections under general/regional anaesthesia. Outpatient-based diathermy or laser ablation is another option, but evidence for its efficacy is mixed and its use is controversial. OBJECTIVE: To systematically review evidence regarding the efficacy and safety of outpatient diathermy and laser ablation for the treatment of recurrent NMIBC. EVIDENCE ACQUISITION: The EMBASE, MEDLINE/PubMed, and Cochrane Library were searched from inception to June 26, 2020. All studies evaluating the use of diathermy or laser ablation for bladder tumours (new or recurrent) in an outpatient setting under local anaesthetic were included. Two reviewers independently screened all articles, searched the reference lists of retrieved articles, and performed the data extraction. The quality of evidence and risk of bias were assessed using the GRADE and ROBINS-I tools. EVIDENCE SYNTHESIS: The search yielded 1328 studies. After excluding duplicates, 1319 titles and abstracts were screened and 17 studies (1584 patients) were eligible for inclusion in the final review. The majority of patients had small, low-grade tumours, but there was heterogeneity in the inclusion criteria. Overall, laser ablation and diathermy resulted in mean recurrence rates of 47% and 32% at follow-up of 22-38 mo, respectively, with a mean progression rate of 3-12% (low certainty of evidence). Both procedures were well tolerated, with low pain scores and low periprocedural complication rates (moderate certainty of evidence). CONCLUSIONS: Outpatient diathermy and laser ablation have good short-term efficacy in patients with low-grade NMIBC and reduce the need for intervention under general/regional anaesthesia. The procedures are well tolerated with low complication rates. The overall certainty of evidence is low, with heterogeneity between studies and methodological limitations. However, we have highlighted the need for randomised trials with long-term follow-up using standardised risk classification and outcome measures. Despite these limitations, the findings will aid in patient counselling regarding this less invasive treatment option that avoids the morbidity of transurethral resection. PATIENT SUMMARY: Outpatient diathermy and laser ablation have good success rates in treating recurrent low-grade bladder tumours in the short term, avoiding the need for more invasive procedures under general/regional anaesthesia, with low rates of side effects. Further studies are needed to determine whether these treatments remain safe and effective in the long term.

Patient- and Tumour-related Prognostic Factors for Urinary Incontinence After Radical Prostatectomy for Nonmetastatic Prostate Cancer: A Systematic Review and Meta-analysis.

CONTEXT: While urinary incontinence (UI) commonly occurs after radical prostatectomy (RP), it is unclear what factors increase the risk of UI development. OBJECTIVE: To perform a systematic review of patient- and tumour-related prognostic factors for post-RP UI. The primary outcome was UI within 3 mo after RP. Secondary outcomes included UI at 3-12 mo and ≥12 mo after RP. EVIDENCE ACQUISITION: Databases including Medline, EMBASE, and CENTRAL were searched between January 1990 and May 2020. All studies reporting patient- and tumour-related prognostic factors in univariable or multivariable analyses were included. Surgical factors were excluded. Risk of bias (RoB) and confounding assessments were performed using the Quality In Prognosis Studies (QUIPS) tool. Random-effects meta-analyses were performed for all prognostic factor, where possible. EVIDENCE SYNTHESIS: A total of 119 studies (5 randomised controlled trials, 24 prospective, 88 retrospective, and 2 case-control studies) with 131 379 patients were included. RoB was high for study participation and confounding; moderate to high for statistical analysis, study attrition, and prognostic factor measurement; and low for outcome measurements. Significant prognostic factors for postoperative UI within 3 mo after RP were age (odds ratio [OR] per yearly increase 1.04, 95% confidence interval [CI] 1.03-1.05), membranous urethral length (MUL; OR per 1-mm increase 0.81, 95% CI 0.74-0.88), prostate volume (PV; OR per 1-ml increase 1.005, 95% CI 1.000-1.011), and Charlson comorbidity index (CCI; OR 1.28, 95% CI 1.09-1.50). CONCLUSIONS: Increasing age, shorter MUL, greater PV, and higher CCI are independent prognostic factors for UI within 3 mo after RP, with all except CCI remaining prognostic at 3-12 mo. PATIENT SUMMARY: We reviewed the literature to identify patient and disease factors associated with urinary incontinence after surgery for prostate cancer. We found increasing age, larger prostate volume, shorter length of a section of the urethra (membranous urethra), and lower fitness were associated with worse urinary incontinence for the first 3 mo after surgery, with all except lower fitness remaining predictive at 3-12 mo.

Benefits and Harms of Conservative, Pharmacological, and Surgical Management Options for Women with Bladder Outlet Obstruction: A Systematic Review from the European Association of Urology Non-neurogenic Female LUTS Guidelines Panel.

CONTEXT: While the management of bladder outlet obstruction (BOO) in men has been a topic of several systematic reviews and meta-analyses, no such evidence base exists for female BOO. OBJECTIVE: The aim of this systematic review was to evaluate the benefits and harms of therapeutic interventions for the management of BOO in women. EVIDENCE ACQUISITION: This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. The study protocol was registered with PROSPERO (CRD42020183839). A systematic literature search was performed and updated by a research librarian in May 2021. The study population consisted of adult female patients diagnosed with BOO, who underwent treatment. EVIDENCE SYNTHESIS: Out of 6344 records, we identified 33 studies enrolling 1222 participants, of which only six randomized controlled trials (RCTs) were found. One placebo-controlled crossover randomized trial assessed the role of baclofen in 60 female patients with dysfunctional voiding. The trial met its primary endpoint with a significantly greater decrease in the number of voids per day in the baclofen group (-5.53 vs -2.70; p = 0.001). The adverse events were mild and comparable in both groups (25% vs 20%). One placebo-controlled crossover randomized trial assessed the role of sildenafil in 20 women with Fowler's syndrome. There were significant improvements from baseline in maximum urinary flow rate (Qmax), International Prostate Symptom Score (IPSS), and postvoid residual (PVR), but with no statistically significant difference when compared with placebo. In a large RCT including 197 female patients with functional BOO, the alpha-blocker alfuzosin significantly improved IPSS, Qmax, and PVR compared with baseline, but the differences were not statistically significant compared with the placebo group. Several small single-arm prospective series reported improvement of BOO-related symptoms and voiding parameters with urethroplasty, sling revision, urethral dilation, vaginal pessary, and pelvic organ prolapse repair. CONCLUSIONS: Evidence to support the use of conservative, pharmacological, and surgical treatments for BOO is scarce. PATIENT SUMMARY: According to the present systematic review of the literature, evidence to support the use of conservative, pharmacological, and surgical treatments for either anatomical or functional bladder outlet obstruction is scarce.

Evaluation of Oncological Outcomes and Data Quality in Studies Assessing Nerve-sparing Versus Non-Nerve-sparing Radical Prostatectomy in Nonmetastatic Prostate Cancer: A Systematic Review.

CONTEXT: Surgical techniques aimed at preserving the neurovascular bundles during radical prostatectomy (RP) have been proposed to improve functional outcomes. However, it remains unclear if nerve-sparing (NS) surgery adversely affects oncological metrics. OBJECTIVE: To explore the oncological safety of NS versus non-NS (NNS) surgery and to identify factors affecting the oncological outcomes of NS surgery. EVIDENCE ACQUISITION: Relevant databases were searched for English language articles published between January 1, 1990 and May 8, 2020. Comparative studies for patients with nonmetastatic prostate cancer (PCa) treated with primary RP were included. NS and NNS techniques were compared. The main outcomes were side-specific positive surgical margins (ssPSM) and biochemical recurrence (BCR). Risk of bias (RoB) and confounding assessments were performed. EVIDENCE SYNTHESIS: Out of 1573 articles identified, 18 studies recruiting a total of 21 654 patients were included. The overall RoB and confounding were high across all domains. The most common selection criteria for NS RP identified were characteristic of low-risk disease, including low core-biopsy involvement. Seven studies evaluated the link with ssPSM and showed an increase in ssPSM after adjustment for side-specific confounders, with the relative risk for NS RP ranging from 1.50 to 1.53. Thirteen papers assessing BCR showed no difference in outcomes with at least 12 mo of follow-up. Lack of data prevented any subgroup analysis for potentially important variables. The definitions of NS were heterogeneous and poorly described in most studies. CONCLUSIONS: Current data revealed an association between NS surgery and an increase in the risk of ssPSM. This did not translate into a negative impact on BCR, although follow-up was short and many men harbored low-risk PCa. There are significant knowledge gaps in terms of how various patient, disease, and surgical factors affect outcomes. Adequately powered and well-designed prospective trials and cohort studies accounting for these issues with long-term follow-up are recommended. PATIENT SUMMARY: Neurovascular bundles (NVBs) are structures containing nerves and blood vessels. The NVBs close to the prostate are responsible for erections. We reviewed the literature to determine if a technique to preserve the NVBs during removal of the prostate causes worse cancer outcomes. We found that NVB preservation was poorly defined but, if applied, was associated with a higher risk of cancer at the margins of the tissue removed, even in patients with low-risk prostate cancer. The long-term importance of this finding for patients is unclear. More data are needed to provide recommendations.

A Systematic Review of the Impact of Surgeon and Hospital Caseload Volume on Oncological and Nononcological Outcomes After Radical Prostatectomy for Nonmetastatic Prostate Cancer.

CONTEXT: The impact of surgeon and hospital volume on outcomes after radical prostatectomy (RP) for localised prostate cancer (PCa) remains unknown. OBJECTIVE: To perform a systematic review on the association between surgeon or hospital volume and oncological and nononcological outcomes following RP for PCa. EVIDENCE ACQUISITION: Medline, Medline In-Process, Embase, and the Cochrane Central Register of Controlled Trials were searched. All comparative studies for nonmetastatic PCa patients treated with RP published between January 1990 and May 2020 were included. For inclusion, studies had to compare hospital or surgeon volume, defined as caseload per unit time. Main outcomes included oncological (including prostate-specific antigen persistence, positive surgical margin [PSM], biochemical recurrence, local and distant recurrence, and cancer-specific and overall survival) and nononcological (perioperative complications including need for blood transfusion, conversion to open procedure and within 90-d death, and continence and erectile function) outcomes. Risk of bias (RoB) and confounding assessments were undertaken. Both a narrative and a quantitative synthesis were planned if the data allowed. EVIDENCE SYNTHESIS: Sixty retrospective comparative studies were included. Generally, increasing surgeon and hospital volumes were associated with lower rates of mortality, PSM, adjuvant or salvage therapies, and perioperative complications. Combining group size cut-offs as used in the included studies, the median threshold for hospital volume at which outcomes start to diverge is 86 (interquartile range [IQR] 35-100) cases per year. In addition, above this threshold, the higher the caseload, the better the outcomes, especially for PSM. RoB and confounding were high for most domains. CONCLUSIONS: Higher surgeon and hospital volumes for RP are associated with lower rates of PSMs, adjuvant or salvage therapies, and perioperative complications. This association becomes apparent from a caseload of >86 (IQR 35-100) per year and may further improve hereafter. Both high- and low-volume centres should measure their outcomes, make them publicly available, and improve their quality of care if needed. PATIENT SUMMARY: We reviewed the literature to determine whether the number of prostate cancer operations (radical prostatectomy) performed in a hospital affects the outcomes of surgery. We found that, overall, hospitals with a higher number of operations per year have better outcomes in terms of cancer recurrence and complications during or after hospitalisation. However, it must be noted that surgeons working in hospitals with lower annual operations can still achieve similar or even better outcomes. Therefore, making hospital's outcome data publicly available should be promoted internationally, so that patients can make an informed decision where they want to be treated.

A Systematic Review of Outcome Reporting, Definition and Measurement Heterogeneity in Non-Muscle Invasive Bladder Cancer Effectiveness Trials of Adjuvant, Prophylactic Treatment After Transurethral Resection.

BACKGROUND: Heterogenous outcome reporting in non-muscle-invasive bladder cancer (NMIBC) effectiveness trials of adjuvant treatment after transurethral resection (TURBT) has been noted in systematic reviews (SRs). This hinders comparing results across trials, combining them in meta-analyses, and evidence-based decision-making for patients and clinicians. OBJECTIVE: We aimed to systematically review the extent of reporting and definition heterogeneity. METHODS: We included randomized controlled trials (RCTs) identified from SRs comparing adjuvant treatments after TURBT or TURBT alone in patients with NMIBC (with or without carcinoma in situ) published between 2000-2020. Abstracts and full texts were screened independently by two reviewers. Data were extracted by one reviewer and checked by another. RESULTS: We screened 807 abstracts; from 15 SRs, 57 RCTs were included. Verbatim outcome names were coded to standard outcome names and organised using the Williamson and Clarke taxonomy. Recurrence (98%), progression (74%), treatment response (in CIS studies) (40%), and adverse events (77%) were frequently reported across studies. However, overall (33%) and cancer-specific (33%) survival, treatment completion (17%) and treatment change (37%) were less often reported. Quality of Life (3%) and economic outcomes (2%) were rarely reported. Heterogeneity was evident throughout, particularly in the definitions of progression and recurrence, and how CIS patients were handled in the analysis of studies with predominantly papillary patients, highlighting further issues with the definition of recurrence and progression vs treatment response for CIS patients. Data reporting was also inconsistent, with some trials reporting event rates at various time-points and others reporting time-to-event with or without Hazard Ratios. Adverse events were inconsistently reported. QoL data was absent in most trials. CONCLUSIONS: Heterogenous outcome reporting is evident in NMIBC effectiveness trials. This has profound implications for meta-analyses, SRs and evidence-based treatment decisions. A core outcome set is required to reduce heterogeneity. PATIENT SUMMARY: This systematic review found inconsistencies in outcome definitions and reporting, pointing out the urgent need for a core outcome set to help improve evidence-based treatment decisions.

Benefits and Risks of Primary Treatments for High-risk Localized and Locally Advanced Prostate Cancer: An International Multidisciplinary Systematic Review.

CONTEXT: The optimal treatment for men with high-risk localized or locally advanced prostate cancer (PCa) remains unknown. OBJECTIVE: To perform a systematic review of the existing literature on the effectiveness of the different primary treatment modalities for high-risk localized and locally advanced PCa. The primary oncological outcome is the development of distant metastases at ≥5 yr of follow-up. Secondary oncological outcomes are PCa-specific mortality, overall mortality, biochemical recurrence, and need for salvage treatment with ≥5 yr of follow-up. Nononcological outcomes are quality of life (QoL), functional outcomes, and treatment-related side effects reported. EVIDENCE ACQUISITION: Medline, Medline In-Process, Embase, and the Cochrane Central Register of Randomized Controlled Trials were searched. All comparative (randomized and nonrandomized) studies published between January 2000 and May 2019 with at least 50 participants in each arm were included. Studies reporting on high-risk localized PCa (International Society of Urologic Pathologists [ISUP] grade 4-5 [Gleason score {GS} 8-10] or prostate-specific antigen [PSA] >20 ng/ml or ≥ cT2c) and/or locally advanced PCa (any PSA, cT3-4 or cN+, any ISUP grade/GS) or where subanalyses were performed on either group were included. The following primary local treatments were mandated: radical prostatectomy (RP), external beam radiotherapy (EBRT) (≥64 Gy), brachytherapy (BT), or multimodality treatment combining any of the local treatments above (±any systemic treatment). Risk of bias (RoB) and confounding factors were assessed for each study. A narrative synthesis was performed. EVIDENCE SYNTHESIS: Overall, 90 studies met the inclusion criteria. RoB and confounding factors revealed high RoB for selection, performance, and detection bias, and low RoB for correction of initial PSA and biopsy GS. When comparing RP with EBRT, retrospective series suggested an advantage for RP, although with a low level of evidence. Both RT and RP should be seen as part of a multimodal treatment plan with possible addition of (postoperative) RT and/or androgen deprivation therapy (ADT), respectively. High levels of evidence exist for EBRT treatment, with several randomized clinical trials showing superior outcome for adding long-term ADT or BT to EBRT. No clear cutoff can be proposed for RT dose, but higher RT doses by means of dose escalation schemes result in an improved biochemical control. Twenty studies reported data on QoL, with RP resulting mainly in genitourinary toxicity and sexual dysfunction, and EBRT in bowel problems. CONCLUSIONS: Based on the results of this systematic review, both RP as part of multimodal treatment and EBRT + long-term ADT can be recommended as primary treatment in high-risk and locally advanced PCa. For high-risk PCa, EBRT + BT can also be offered despite more grade 3 toxicity. Interestingly, for selected patients, for example, those with higher comorbidity, a shorter duration of ADT might be an option. For locally advanced PCa, EBRT + BT shows promising result but still needs further validation. In this setting, it is important that patients are aware that the offered therapy will most likely be in the context a multimodality treatment plan. In particular, if radiation is used, the combination of local with systemic treatment provides the best outcome, provided the patient is fit enough to receive both. Until the results of the SPCG15 trial are known, the optimal local treatment remains a matter of debate. Patients should at all times be fully informed about all available options, and the likelihood of a multimodal approach including the potential side effects of both local and systemic treatment. PATIENT SUMMARY: We reviewed the literature to see whether the evidence from clinical studies would tell us the best way of curing men with aggressive prostate cancer that had not spread to other parts of the body such as lymph glands or bones. Based on the results of this systematic review, there is good evidence that both surgery and radiation therapy are good treatment options, in terms of prolonging life and preserving quality of life, provided they are combined with other treatments. In the case of surgery this means including radiotherapy (RT), and in the case of RT this means either hormonal therapy or combined RT and brachytherapy.

What are the benefits and harms of testosterone therapy for male sexual dysfunction?-a systematic review.

The role of Testosterone Therapy (TTh) in the management of male sexual dysfunction remains unclear. Objective of the authors was to systematically review the relevant literature assessing the benefits and harms of TTh in men with sexual dysfunction. EMBASE, MEDLINE, Cochrane Systematic Reviews-Cochrane Central Register of Controlled Trials (CENTRAL) (Cochrane HTA, DARE, HEED), Google Scholar, WHO international Clinical Trials Registry Platform Search Portal, CINAHL databases and clinicaltrial.gov were searched systematically in March 2015 and an updated search was performed in March 2016. Randomized and non-randomized comparative studies assessing the benefits and harms of TTh in hypogonadal, borderline eugonadal and eugonadal men suffering from sexual dysfunction were included. Risk of bias and confounding assessments were performed. A narrative synthesis was undertaken. Of the 6410 abstracts identified, 36 studies were judged to be eligible for inclusion, including 25 randomized clinical trials (RCTs) and 11 non-randomized comparative studies (NRCSs), recruiting a total of 4944 patients. RCTs were judged to have low or unclear risk of bias, while NRCSs had high risk of bias and thus, overall quality of evidence was judged to be at least unclear. Based on the evidence mainly provided by the RCTs included in this systematic review, TTh could be considered for men with low or low-normal testosterone levels and problems with their sexual desire, erectile function and satisfaction derived from intercourse and overall sexual life. The exact testosterone formulation, dosage and duration of treatment remain to be clarified, while the safety profile of TTh also remains unclear. TTh could be used with caution in hypogonadal and most probably borderline eugonadal men to manage disorders of sexual desire, erectile function and sexual satisfaction. The overall low-to-moderate evidence quality highlights the need for robust and adequately designed clinical trials.

Oncological Outcomes of Laparoscopic Nephroureterectomy Versus Open Radical Nephroureterectomy for Upper Tract Urothelial Carcinoma: An European Association of Urology Guidelines Systematic Review.

CONTEXT: Most series have suggested better perioperative outcomes of laparoscopic radical nephroureterectomy (RNU) over open RNU. However, the oncological safety of laparoscopic RNU remains controversial. OBJECTIVE: To systematically review all relevant literature comparing oncological outcomes of open versus laparoscopic RNU. EVIDENCE ACQUISITION: A systematic literature search using the Medline, Embase, and Cochrane databases and clinicaltrial.gov was performed in December 2014 and updated in August 2016. Randomised controlled trials (RCTs) and prospective or retrospective nonrandomised comparative studies comparing the oncological outcomes of any laparoscopic RNU with those of open RNU were included. The primary outcome was cancer-specific survival. The risk of bias (RoB) was assessed using Cochrane RoB tools. A narrative synthesis of the evidence is presented. EVIDENCE SYNTHESIS: Overall, 42 studies were included, which accounted for 7554 patients: 4925 in the open groups and 2629 in the laparoscopic groups. Most included studies were retrospective comparative series. Only one RCT was found. RoB and confounding were high in most studies. No study compared the oncological outcomes of robotic RNU with those of open RNU. Bladder cuff excision in laparoscopic groups was performed via an open approach in most studies, with only three studies reporting laparoscopic removal of the bladder cuff. Port-site metastasis rates ranged from 0% to 2.8%. No significant difference in oncological outcomes was reported in most series. However, three studies, including the only RCT, reported significantly poorer oncological outcomes in patients who underwent laparoscopic RNU, especially in the subgroups of patients with locally advanced (pT3/pT4) or high-grade upper tract urothelial carcinoma (UTUC), as well as in instances when the bladder cuff was excised laparoscopically. CONCLUSIONS: The current available evidence suggests that the oncological outcomes of laparoscopic RNU may be poorer than those of open RNU when bladder cuff is excised laparoscopically and in patients with locally advanced high-risk (pT3/pT4 and/or high-grade) UTUC. PATIENT SUMMARY: We reviewed the literature comparing the outcomes of two different surgical procedures for the treatment of upper tract urothelial carcinoma. Open radical nephroureterectomy is a surgical procedure in which the kidney is removed through a large incision in the abdomen, while in laparoscopic radical nephroureterectomy, the kidney is removed through a number of small incisions. Our findings suggest that the outcomes of laparoscopic radical nephroureterectomy may be poorer than those of open radical nephroureterectomy, particularly when the bladder cuff is also required to be removed. Laparoscopic radical nephroureterectomy may also be less effective in patients with locally advanced (pT3/pT4) or high-grade upper tract urothelial carcinomas.

Potential Benefit of Lymph Node Dissection During Radical Nephroureterectomy for Upper Tract Urothelial Carcinoma: A Systematic Review by the European Association of Urology Guidelines Panel on Non-muscle-invasive Bladder Cancer.

CONTEXT: The oncological efficacy of routine lymphadenectomy (lymph node dissection [LND]) at the time of radical nephroureterectomy (RNU) remains controversial. OBJECTIVE: To systematically review the available literature assessing the impact of LND in upper tract urothelial carcinoma (UTUC) patients. EVIDENCE ACQUISITION: Embase, Medline, and Cochrane databases were searched for all studies comparing outcomes of patients undergoing RNU without LND versus any form of LND. We identified nine retrospective studies eligible for inclusion in this systematic review. We took cancer-specific survival (CSS) as the primary end point, and performed a narrative review and risk of bias assessment. EVIDENCE SYNTHESIS: Six studies compared outcomes of no LND versus LND. Three studies compared complete LND versus incomplete LND versus no LND. The incidence of pN+ in patients with high-stage (≥pT2) tumours ranged from 14.3% to 40%. Pre- and postoperative characteristics differed among the study groups, potentially biasing the results, as demonstrated by the risk of bias assessment, potentially favouring the LND group. Oncological outcomes such as cancer-specific, overall, recurrence-free, and metastasis-free survival were reviewed, demonstrating a survival benefit with LND in high-stage disease of the renal pelvis. CONCLUSIONS: Template-based and complete LND improves CSS in patients with high-stage (≥pT2) UTUC and reduces the risk of local recurrence. The impact of LND in ureteral tumours remains uncertain. PATIENT SUMMARY: Studies comparing radical nephroureterectomy with or without the removal of nodes (lymph node dissection [LND]) were analysed. LND improves survival in patients with high-stage disease of the renal pelvis, if it is performed according to an anatomical template-based approach.

Effectiveness and Harms of Using Kidneys with Small Renal Tumors from Deceased or Living Donors as a Source of Renal Transplantation: A Systematic Review.

CONTEXT: Kidney transplantation is the best treatment for patients with end-stage renal disease. Incidence of small renal masses (SRMs), which most frequently are renal cell carcinomas (RCCs), is highest in patients aged >60 yr. The increasing age of donors can lead to the diagnosis of a higher number of SRMs when assessing the patient for transplantation, and so can theoretically decrease the number of kidneys suitable for transplantation. Aiming to increase the pool of kidneys suitable for transplantation, a number of studies have reported their experience using kidneys with SRMs for transplantation. OBJECTIVE: To systematically review all available evidence on the effectiveness and harm of using kidneys with SRMs as a source of transplantation. EVIDENCE ACQUISITION: A computerized bibliographic search of the Medline, Embase, and Cochrane databases was performed for all studies reporting outcomes of adult renal transplantation using kidneys with SRMs. EVIDENCE SYNTHESIS: Nineteen studies enrolling 109 patients were included and synthesized narratively. The mean recipient age was 44.2 yr, and kidneys used were retrieved from living donors in 86% (94/109) of cases. Tumor excision was performed ex vivo in all cases except for two. The vast majority of excised tumors were RCCs (88/109 patients), and clear-cell subtype was most common. The mean tumor size was 2cm (range 0.5-6.0cm) and tumor grade was G1-G2 in 93% (75/81) of patients. With a mean follow-up of 39.9 mo, overall survival rates at 1, 3, and 5 yr were 97.7%, 95.4%, and 92%, respectively, and the mean graft survival rates 99.2%, 95%, and 95.6%, respectively. Only one local relapse occurred 9 yr after transplantation, which was managed conservatively. Functional outcomes, although infrequently reported, appear to be similar to those of conventional transplants, with 1.6% of these patients needing reoperation. CONCLUSIONS: The current literature, although with low-level evidence, suggests that kidneys with excised SRMs are an acceptable source of transplantation without compromising oncological outcomes and with similar functional outcomes to other donor kidneys. PATIENT SUMMARY: Renal transplantation using a kidney with a small renal mass does not appear to increase the risk of cancer recurrence and can be a good option for selected patients after appropriate counseling and allocation.