Muhammad Imran Omar

Systematic review of oncological outcomes following surgical management of localised renal cancer.

CONTEXT Renal cell carcinoma (RCC) accounts for 2-3% of adult malignancies. There remain uncertainties over the oncological outcomes for the surgical management of localised RCC. OBJECTIVE Systematically review relevant literature comparing oncological outcomes of surgical management of localised RCC (T1-2N0M0). EVIDENCE ACQUISITION Relevant databases including Medline, Embase, and the Cochrane Library were searched up to October 2010, and an updated scoping search was performed up to January 2012. 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 main outcomes were overall survival, cancer-specific survival, recurrence, and metastases. The Cochrane risk of bias tool was used to assess RCTs, and an extended version was used to assess nonrandomised studies (NRSs). The quality of evidence was assessed using Grading of Recommendations Assessment, Development, and Evaluation (GRADE). EVIDENCE SYNTHESIS A total of 4580 abstracts and 389 full-text articles were assessed. Thirty-four studies met the inclusion criteria (6 RCTs and 28 NRSs). Meta-analyses were planned but were deemed inappropriate due to data heterogeneity. There were high risks of bias and low-quality evidence across the evidence base. Open radical nephrectomy and open partial nephrectomy showed similar cancer-specific and overall survival, but when both open and laparoscopic approaches are considered together, the evidence showed improved survival for partial nephrectomy for tumours ≤4cm. The overall evidence suggests either equivalent or better survival with partial nephrectomy. Laparoscopic radical nephrectomy offered equivalent survival to open radical nephrectomy, and all laparoscopic approaches achieved equivalent survival. Open and laparoscopic partial nephrectomy achieved equivalent survival. The issue of ipsilateral adrenalectomy or complete lymph node dissection with radical nephrectomy or partial nephrectomy remains unresolved. CONCLUSIONS The evidence base suggests localised RCCs are best managed by nephron-sparing surgery where technically feasible. However, the current evidence base has significant limitations due to studies of low methodological quality marked by high risks of bias.

Systematic Review of Perioperative and Quality-of-life Outcomes Following Surgical Management of Localised Renal Cancer

CONTEXT For the treatment of localised renal cell carcinoma (RCC), uncertainties remain over the perioperative and quality-of-life (QoL) outcomes for the many different surgical techniques and approaches of nephrectomy. Controversy also remains on whether newer minimally invasive nephron-sparing interventions offer better QoL and perioperative outcomes, and whether adrenalectomy and lymphadenectomy should be performed simultaneously with nephrectomy. These non-oncological outcomes are important because they may have a considerable impact on localised RCC treatment decision making. OBJECTIVE To review systematically all the relevant published literature comparing perioperative and QoL outcomes of surgical management of localised RCC (T1-2N0M0). EVIDENCE ACQUISITION Relevant databases including Medline, Embase, and the Cochrane Library were searched up to January 2012. Randomised controlled trials (RCTs) or quasi-randomised controlled trials, prospective observational studies with controls, retrospective matched-pair studies, and comparative studies from well-defined registries/databases were included. The outcome measures were QoL, analgesic requirement, length of hospital stay, time to normal activity level, surgical morbidity and complications, ischaemia time, renal function, blood loss, length of operation, need for blood transfusion, and perioperative mortality. The Cochrane risk of bias tool was used to assess RCTs, and an extended version was used to assess nonrandomised studies (NRSs). The quality of evidence was assessed using Grading of Recommendations, Assessment, Development, and Evaluation. EVIDENCE SYNTHESIS A total of 4580 abstracts and 380 full-text articles were assessed, and 29 studies met the inclusion criteria (7 RCTs and 22 NRSs). There were high risks of bias and low-quality evidence for studies meeting the inclusion criteria. There is good evidence indicating that partial nephrectomy results in better preservation of renal function and better QoL outcomes than radical nephrectomy regardless of technique or approach. Regarding radical nephrectomy, the laparoscopic approach has better perioperative outcomes than the open approach, and there is no evidence of a difference between the transperitoneal and retroperitoneal approaches. Alternatives to standard laparoscopic radical nephrectomy (LRN) such as hand-assisted, robot-assisted, or single-port techniques appear to have similar perioperative outcomes. There is no good evidence to suggest that minimally invasive procedures such as cryotherapy or radiofrequency ablation have superior perioperative or QoL outcomes to nephrectomy. Regarding concomitant lymphadenectomy during nephrectomy, there were low event rates for complications, and no definitive difference was observed. There was no evidence to base statements about concomitant ipsilateral adrenalectomy during nephrectomy. CONCLUSIONS Partial nephrectomy results in significantly better preservation of renal function over radical nephrectomy. For tumours where partial nephrectomy is not technically feasible, there is no evidence that alternative procedures or techniques are better than LRN in terms of perioperative or QoL outcomes. In making treatment decisions, perioperative and QoL outcomes should be considered in conjunction with oncological outcomes. Overall, there was a paucity of data regarding QoL outcomes, and when reported, both QoL and perioperative outcomes were inconsistently defined, measured, or reported. The current evidence base has major limitations due to studies of low methodological quality marked by high risks of bias.

Systematic review and meta-analysis of the clinical effectiveness of bipolar compared with monopolar transurethral resection of the prostate (TURP)

To compare monopolar and bipolar transurethral resection of the prostate (TURP) for clinical effectiveness and adverse events. We conducted an electronic search of MEDLINE, Embase, CENTRAL, Science Citation Index, and also searched reference lists of articles and abstracts from conference proceedings for randomised controlled trials (RCTs) comparing monopolar and bipolar TURP. Two reviewers independently undertook data extraction and assessed the risk of bias in the included trials using the tool recommended by the Cochrane Collaboration. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. From the 949 abstracts that were identified, 94 full texts were assessed for eligibility and a total of 24 trials were included in the review. No statistically significant differences were found in terms of International Prostate Symptom Score (IPSS) or health‐related quality of life (HRQL) score. Results for maximum urinary flow rate were significant at 3, 6 and 12 months (all P < 0.001), but no clinically significant differences were found and the meta‐analysis showed evidence of heterogeneity Bipolar TURP was associated with fewer adverse events including transurethral resection syndrome (risk ratio [RR] 0.12, 95% confidence interval [CI] 0.05–0.31, P < 0.001), clot retention (RR 0.48, 95% CI 0.30–0.77, P = 0.002) and blood transfusion (RR 0.53, 95% CI 0.35–0.82, P = 0.004) Several major methodological limitations were identified in the included trials; 22/24 trials had a short follow‐up of ≤1 year, there was no evidence of a sample size calculation in 20/24 trials and the application of GRADE showed the evidence for most of the assessed outcomes to be of moderate quality, including all those in which statistical differences were found. Whilst there is no overall difference between monopolar and bipolar TURP for clinical effectiveness, bipolar TURP is associated with fewer adverse events and therefore has a superior safety profile. Various methodological limitations were highlighted in the included trials and as such the results of this review should be interpreted with caution. There is a need for further well‐conducted, multicentre RCTs with long‐term follow‐up data.

Urological cancer care pathways: development and use in the context of systematic reviews and clinical practice guidelines

BackgroundMaking healthcare treatment decisions is a complex process involving a broad stakeholder base including patients, their families, health professionals, clinical practice guideline developers and funders of healthcare.MethodsThis paper presents a review of a methodology for the development of urological cancer care pathways (UCAN care pathways), which reflects an appreciation of this broad stakeholder base. The methods section includes an overview of the steps in the development of the UCAN care pathways and engagement with clinical content experts and patient groups.ResultsThe development process is outlined, the uses of the urological cancer care pathways discussed and the implications for clinical practice highlighted. The full set of UCAN care pathways is published in this paper. These include care pathways on localised prostate cancer, locally advanced prostate cancer, metastatic prostate cancer, hormone-resistant prostate cancer, localised renal cell cancer, advanced renal cell cancer, testicular cancer, penile cancer, muscle invasive and metastatic bladder cancer and non-muscle invasive bladder cancer.ConclusionThe process provides a useful framework for improving urological cancer care through evidence synthesis, research prioritisation, stakeholder involvement and international collaboration. Although the focus of this work is urological cancers, the methodology can be applied to all aspects of urology and is transferable to other clinical specialties.

Urodynamic studies for management of urinary incontinence in children and adults: A short version Cochrane systematic review and meta‐analysis

Urodynamic tests are used to investigate people who have urinary incontinence or other urinary symptoms in order to make an objective diagnosis. The investigations are invasive and time consuming.

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.

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.

Corrigendum to “Systematic Review of Oncological Outcomes Following Surgical Management of Localised Renal Cancer” [Eur Urol 2012;61:972–93]

Steven MacLennan , Mari Imamura , Marie C. Lapitan , Muhammad Imran Omar , Thomas B.L. Lam , Ana M. Hilvano-Cabungcal , Pam Royle , Fiona Stewart , Graeme MacLennan , Sara J. MacLennan , Steven E. Canfield , Sam McClinton , T.R. Leyshon Griffiths , Börje Ljungberg , James N’Dow *, UCAN Systematic Review Reference Group and the EAU Renal Cancer Guideline Panel a Academic Urology Unit, University of Aberdeen, Aberdeen, UK; b University of the Philippines-Manila, Manila, Philippines; c Department of Urology, Aberdeen Royal Infirmary, Aberdeen, UK; d Department of Public Health, University of Aberdeen, UK; e Health Services Research Unit, University of Aberdeen, UK; f Division of Urology, University of Texas Medical School at Houston, Houston, TX, USA; g Department of Urology, University Hospitals of Leicester NHS Trust, Leicester General Hospital, Leicester, UK; h Department of Surgical and Perioperative Sciences, Urology and Andrology, Umeå, University, Umeå, Sweden

Re: Maria Carmen Mir, Ithaar Derweesh, Francesco Porpiglia, Homayoun Zargar, Alexandre Mottrie, Riccardo Autorino. Partial Nephrectomy Versus Radical Nephrectomy for Clinical T1b and T2 Renal Tumors: A Systematic Review and Meta-analysis of Comparative Studies. Eur Urol. 2017;71:606–17

We commend Mir et al [1] for their systematic review (SR) that attempted to clarify uncertainties in the optimal surgical treatment (partial nephrectomy [PN] or radical nephrectomy [RN]) for patients with large (T1b–T2) renal masses. However, their decision to combine the results of individual retrospective studies with a high risk of selection bias and confounding in a meta-analysis (MA) is methodologically flawed and may result in erroneous and misleading conclusions. There are imbalances between the PN and RN groups in the studies included with regard to age, comorbidities, tumor size and stage, and biological behavior. These imbalances may have a greater impact on patient outcome than the choice of PN or RN. When used appropriately, MA can provide the best estimate of a treatment effect size from the pooled weighted averages of the results from individual trials. MAs of well-conducted randomized controlled trials (RCTs) are based on the assumption that each trial provides an unbiased estimate of the treatment effect, so that the overall combined effect will provide a more precise, unbiased estimate of the treatment effect. By contrast, observational studies produce estimates that may deviate from the truth owing to the effects of confounding factors, the influence of bias, or both [2]. MAs of observational studies will simply compound these errors and provide pooled estimates that may be seriously misleading, and even wrong. Unfortunately, the results of such an MA may be interpreted as having more credibility than it deserves. Instead, a careful analysis of the possible sources of methodological, clinical, and statistical heterogeneity between studies in the SR with a narrative rather than a quantitative synthesis of the evidence will provide more insight than calculation of an overall measure of effect that is likely to be biased [3]. Our concern is especially relevant as several examples of important selection biases