Yuhong Yuan

Prognostic Performance and Reproducibility of the 1973 and 2004/2016 World Health Organization Grading Classification Systems in Non–muscle-invasive Bladder Cancer: A European Association of Urology Non-muscle Invasive Bladder Cancer Guidelines Panel Systematic Review

CONTEXT Tumour grade is an important prognostic indicator in non-muscle-invasive bladder cancer (NMIBC). Histopathological classifications are limited by interobserver variability (reproducibility), which may have prognostic implications. European Association of Urology NMIBC guidelines suggest concurrent use of both 1973 and 2004/2016 World Health Organization (WHO) classifications. OBJECTIVE To compare the prognostic performance and reproducibility of the 1973 and 2004/2016 WHO grading systems for NMIBC. EVIDENCE ACQUISITION A systematic literature search was undertaken incorporating Medline, Embase, and the Cochrane Library. Studies were critically appraised for risk of bias (QUIPS). For prognosis, the primary outcome was progression to muscle-invasive or metastatic disease. Secondary outcomes were disease recurrence, and overall and cancer-specific survival. For reproducibility, the primary outcome was interobserver variability between pathologists. Secondary outcome was intraobserver variability (repeatability) by the same pathologist. EVIDENCE SYNTHESIS Of 3593 articles identified, 20 were included in the prognostic review; three were eligible for the reproducibility review. Increasing tumour grade in both classifications was associated with higher disease progression and recurrence rates. Progression rates in grade 1 patients were similar to those in low-grade patients; progression rates in grade 3 patients were higher than those in high-grade patients. Survival data were limited. Reproducibility of the 2004/2016 system was marginally better than that of the 1973 system. Two studies on repeatability showed conflicting results. Most studies had a moderate to high risk of bias. CONCLUSIONS Current grading classifications in NMIBC are suboptimal. The 1973 system identifies more aggressive tumours. Intra- and interobserver variability was slightly less in the 2004/2016 classification. We could not confirm that the 2004/2016 classification outperforms the 1973 classification in prediction of recurrence and progression. PATIENT SUMMARY This article summarises the utility of two different grading systems for non-muscle-invasive bladder cancer. Both systems predict progression and recurrence, although pathologists vary in their reporting; suggestions for further improvements are made.

Conflict of Evidence: Resolving Discrepancies When Findings from Randomized Controlled Trials and Meta-analyses Disagree

CONTEXT Clinicians and treatment guideline developers are faced with a dilemma when the results of a new, large, well-conducted randomized controlled trial (RCT) are in direct conflict with the results of a previous systematic review (SR) and meta-analysis (MA). OBJECTIVE To explore and discuss possible reasons for disagreement in results from SRs/MAs and RCTs and to provide guidance to clinicians and guideline developers for making well-informed treatment decisions and recommendations in the face of conflicting data. EVIDENCE ACQUISITION The advantages and limitations of RCTs and SRs/MAs are reviewed. Two practical examples that have a direct bearing on European Association of Urology guidelines on treatment recommendations are discussed in detail to illustrate the points to be considered when conflicts exist between the results of large RCTs and SRs/MAs. EVIDENCE SYNTHESIS RCTs are the gold standard for providing evidence of the effectiveness of interventions. However, concerns regarding the internal and external validity of an RCT may limit its applicability to clinical practice. SRs/MAs synthesize all evidence related to a given research question, but two urologic examples show that the validity of the results depends on the quality of the individual studies, the clinical and methodological heterogeneity of the studies, and publication bias. CONCLUSIONS Although SRs/MAs can provide a higher level of evidence than RCTs, the quality of the evidence from both RCTs and SRs/MAs should be investigated when their results conflict to determine which source provides the better evidence. Guideline developers should have a well-defined and robust process to assess the evidence from MAs and RCTs when such conflicts exist. PATIENT SUMMARY We discuss the advantages and limitations of using data from randomized controlled trials and systematic reviews/meta-analyses in informing clinical practice when there are conflicting results. We provide guidance on how such conflicts should be dealt with by guideline organizations.

Oncological and functional outcomes of sexual function-preserving cystectomy compared with standard radical cystectomy in men: A systematic review

INTRODUCTION Different sexual function-preserving surgical techniques aimed at improving voiding and sexual function in patients undergoing radical cystectomy for bladder cancer have been described. The objective of this systematic review is to determine the effect of sexual function-preserving cystectomy (SPC) on functional and oncological outcomes. MATERIALS AND METHODS Relevant databases were searched covering the time frame 2000 to 2015. All publications presenting data on any type of SPC reporting oncological or functional outcomes with a minimum follow-up of 1 year were identified. Comparative studies including a minimum of 30 patients and single-arm case series with a minimum of 50 patients were selected. No language restrictions were applied. RESULTS In a total of 8,517 identified abstracts, 12 studies were eligible for inclusion. SPC described included prostate-, capsule-, seminal vesicle, and nerve-sparing techniques. Local recurrence ranged from 1.2% to 61.1% (vs. 16.0%-55.0% in the control group) and metastatic disease from 0% to 33.3% (vs. 33.0%). No differences were found in comparative studies reporting oncological outcomes. Postoperative potency was significantly better in the SPC groups in 6 studies comparing sexual function-preserving cystectomy vs. radical cystectomy (P<0.05). No major effect on continence was found. Overall, there was moderate to high risk of bias and confounding. CONCLUSIONS The evidence base for prostate-, capsule-, or nerve-sparing cystectomy suggests that these procedures may yield better sexual outcomes than standard cystectomy, without compromising oncological outcomes. However, the overall quality of the evidence was moderate, and hence if offered, patients must be carefully selected, counseled, and closely monitored.

Tract Sizes in Miniaturized Percutaneous Nephrolithotomy: A Systematic Review from the European Association of Urology Urolithiasis Guidelines Panel

CONTEXT Miniaturized instruments for percutaneous nephrolithotomy (PNL), utilizing tracts sized ≤22 Fr, have been developed in an effort to reduce the morbidity and increase the efficiency of stone removal compared with standard PNL (>22 Fr). OBJECTIVE We systematically reviewed all available evidence on the efficacy and safety of miniaturized PNL for removing renal calculi. EVIDENCE ACQUISITION The review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement. Since it was not possible to perform a meta-analysis, the data were summarized in a narrative synthesis. EVIDENCE SYNTHESIS After screening 2945 abstracts, 18 studies were included (two randomized controlled trials [RCTs], six nonrandomized comparative studies, and 10 case series). Thirteen studies were full-text articles and five were only available as congress abstracts. The size of tracts used in miniaturized procedures ranged from 22 Fr to 4.8 Fr. The largest mean stone size treated using small instruments was 980mm2. Stone-free rates were comparable in miniaturized and standard PNL procedures. Procedures performed with small instruments tended to be associated with significantly lower blood loss, while the procedure duration tended to be significantly longer. Other complications were not notably different between PNL types. Study designs and populations were heterogeneous. Study limitations included selection and outcome reporting bias, as well as a lack of information on relevant confounding factors. CONCLUSIONS The studies suggest that miniaturized PNL is at least as efficacious and safe as standard PNL for the removal of renal calculi. However, the quality of the evidence was poor, drawn mainly from small studies, the majority of which were single-arm case series, and only two of which were RCTs. Furthermore, the tract sizes used and types of stones treated were heterogeneous. Hence, the risks of bias and confounding were high, highlighting the need for more reliable data from RCTs. PATIENT SUMMARY Removing kidney stones via percutaneous nephrolithotomy (PNL) using smaller sized instruments (mini-PNL) appears to be as effective and safe as using larger (traditional) instruments, but more clinical research is needed.

Key Steps in Conducting Systematic Reviews for Underpinning Clinical Practice Guidelines: Methodology of the European Association of Urology

CONTEXT The findings of systematic reviews (SRs) and meta-analyses (MAs) are used for clinical decision making. The European Association of Urology has committed increasing resources into the development of high quality clinical guidelines based on such SRs and MAs. OBJECTIVE In this paper, we have summarised the process of conducting SRs for underpinning clinical practice guidelines under the auspices of the European Association of Urology Guidelines Office. EVIDENCE ACQUISITION The process involves explicit methods and the findings should be reproducible. When conducting a SR, the essential first step is to formulate a clear and answerable research question. An extensive literature search lays the foundation for evidence synthesis. Data are extracted independently by two reviewers and any disagreements are resolved by discussion or arbitration by a third reviewer. EVIDENCE SYNTHESIS In SRs, data for particular outcomes in individual randomised controlled trials may be combined statistically in a meta-analysis to increase power when the studies are similar enough. Biases in studies included in a SR/MA can lead to either an over estimation or an under estimation of true intervention effect size, resulting in heterogeneity in outcome between studies. A number of different tools are available such as Cochrane Risk of Bias assessment tool for randomised controlled trials. In circumstances where there is too much heterogeneity, or when a review has included nonrandomised comparative studies, it is more appropriate to conduct a narrative synthesis. The GRADE tool for assessing quality of evidence strives to be a structured and transparent system, which can be applied to all evidence, regardless of quality. A SR not only identifies, evaluates, and summarises the best available evidence, but also the gaps to be targeted by future studies. CONCLUSIONS SRs and MAs are integral in developing sound clinical practice guidelines and recommendations. PATIENT SUMMARY Clinical practice guidelines should be evidence based, and systematic reviews and meta-analyses are essential in their production. We have discussed the key steps of conducting systematic reviews and meta-analyses in this paper.

Testicular Tumour Size and Rete Testis Invasion as Prognostic Factors for the Risk of Relapse of Clinical Stage I Seminoma Testis Patients Under Surveillance: a Systematic Review by the Testicular Cancer Guidelines Panel

CONTEXT Patients with clinical stage I (CS I) seminoma testis with large primary tumours and/or rete testis invasion (RTI) might have an increased risk of relapse. In recent years, these risk factors have frequently been employed to decide on adjuvant treatment. OBJECTIVE To systematically review the literature on tumour size and RTI as risk factors for relapse in CS I seminoma testis patients under surveillance. EVIDENCE ACQUISITION Relevant databases including Medline, Embase, and the Cochrane Library were searched up to November 2016. Randomised controlled trials (RCTs) or quasi-RCTs, prospective observational studies with controls, retrospective matched-pair studies, and comparative studies from well-defined registries/databases were included. The primary outcome was the rate of relapse and relapse-free survival (RFS). The risk of bias was assessed by the Quality in Prognosis Studies tool. EVIDENCE SYNTHESIS After assessing 3068 abstracts and 80 full-text articles, 20 studies met the inclusion criteria. Although evidence to justify a cut-off of 4cm for size was lacking, it was the most frequently studied. The reported hazard ratio (HR) for the RFS for tumours >4cm was 1.59-2.8. Accordingly, the reported 5-yr RFS ranged from 86.6% to 95.5% and from 73.0% to 82.6% for patients having tumours ≤4 and >4cm, respectively. For tumours with RTI present, the reported HR was 1.4-1.7. The 5-yr RFS ranged from 86.0% to 92.0% and 74.9% to 79.5% for patients without versus those with RTI present, respectively. A meta-analysis was considered inappropriate due to data heterogeneity. CONCLUSIONS Primary tumour size and RTI are associated with the risk of relapse in CS I seminoma testis patients during surveillance. However, in the presence of either risk factor, the vast majority of patients are cured by orchiectomy alone and will not relapse. Furthermore, the evidence on the prognostic value of size and RTI has significant limitations, so prudency is warranted on their routine use in clinical practice. PATIENT SUMMARY Primary testicular tumour size and rete testis invasion are considered to be important prognostic factors for the risk of relapse in patients with clinical stage I seminoma testis. We systematically reviewed all the literature on the prognostic value of these two postulated risk factors. The outcome is that the prognostic power of these factors in the published literature is too low to advocate their routine use in clinical practice and to drive the choice on adjuvant treatment in clinical stage I seminoma testis patients.

Systematic review of the oncological and functional outcomes of pelvic organ-preserving radical cystectomy (RC) compared with standard RC in women who undergo curative surgery and orthotopic neobladder substitution for bladder cancer

Pelvic organ‐preserving radical cystectomy (POPRC) for women may improve postoperative sexual and urinary functions without compromising the oncological outcome compared with standard radical cystectomy (RC).

Outcomes of Early Endoscopic Realignment Versus Suprapubic Cystostomy and Delayed Urethroplasty for Pelvic Fracture-related Posterior Urethral Injuries: A Systematic Review

CONTEXT The evidence base for optimal acute management of pelvic fracture-related posterior urethral injuries needs to be reviewed because of evolving endoscopic techniques. The current standard of care is suprapubic cystostomy followed by delayed urethroplasty. OBJECTIVE To systematically review the evidence base comparing early endoscopic realignment with cystostomy and delayed urethroplasty regarding stricture rate, the need for subsequent procedures, and functional outcomes. EVIDENCE ACQUISITION A systematic search in Medline, Embase, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Review, and www.clinicaltrials.gov without time or language limitations. Both medical subject heading and free text terms as well as variations of root word were searched. Randomised controlled trials (RCTs), nonrandomised comparative studies and single-arm case series were included, as long as ≥10 patients were enrolled. Data were narratively synthesised in light of methodological and clinical heterogeneity. The risk of bias of each included study was assessed. EVIDENCE SYNTHESIS No RCTs were found. Six nonrandomised comparative studies and met inclusion criteria and were selected for data extraction. Noncomparative studies with more than 10 participants were included resulting in seven eligible studies. From the comparative papers the results of 219 patients were reported: 142 in the realignment group and 77 in the group undergoing cystostomy with delayed repair. The noncomparative studies reported on a further 150 cases. An overall stricture rate of 49% was evident in the endoscopic realignment group. Of these patients, 50% (28.1% overall) could be managed by endoscopic procedures and 40.3% (18.5% of intervention group) required anastomotic repair. CONCLUSIONS No RCTs were found and the included nonrandomised studies have heterogeneous populations and a high degree of bias. About half of the patients were free of stricture and thus did not undergo delayed urethroplasty in case early endoscopic realignment had been performed. PATIENT SUMMARY This systematic review of literature of urethral trauma revealed there are no well conducted comparative studies of newer endoscopic treatments versus standard treatments which include more extensive surgery. The results of the reports we selected based on specific characteristics are often influenced by variable factors. After careful analysis of these results we can conclude that the newer endoscopic techniques might resolve the risk of urethral injury due to pubic fractures in about half of the patients. Because of various confounders we cannot identify those patients who would benefit from this procedure or who might be possibly harmed.

The benefits and harms of different extents of lymph node dissection during radical prostatectomy for prostate cancer: A systematic review

Nicola Fossati , Peter-Paul M. Willemse , Thomas Van den Broeck , Roderick C.N. van den Bergh , Cathy Yuhong Yuan , Erik Briers , Joaquim Bellmunt , Michel Bolla , Philip Cornford , Maria De Santis , Ekelechi MacPepple , Ann M. Henry , Malcolm D. Mason , Vsevolod B. Matveev , Henk G. van der Poel , Theo H. van der Kwast , Olivier Rouvière , Ivo G. Schoots , Thomas Wiegel , Thomas B. Lam , Nicolas Mottet , Steven Joniau *

Testicular tumour size and rete testis invasion as prognostic factors for the risk of relapse of clinical stage I seminoma testis patients under surveillance: A systematic review by the Testicular Cancer Guidelines Panel

Department of Urology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands; Department of Urology, Hospital Gregorio Marañón, Madrid, Spain; Department of Urology and Renal Transplantation, Centro Hospitalar e Universitário de Coimbra, Portugal; Division of Gastroenterology and Cochrane UGPD Group, Department of Medicine, Health Sciences Centre, McMaster University, Hamilton, Canada; Department of Urology, AMC University Hospital Amsterdam, The Netherlands; Department of Internal Medicine II, Oncology, Hematology and Stem Cell Transplantation with Section Pneumology, University Hospital Eppendorf, Hamburg, Germany; g Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy; Department of Pathology, Fundació Puigvert, Universitat Autònoma de Barcelona, Barcelona, Spain; Department of Oncology, Akershus University Hospital, Lørenskog, Norway and University of Oslo, Oslo, Norway; Department of Urology, Düsseldorf University Hospital, Heinrich-Heine-University Düsseldorf, Germany