Sara MacLennan

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.

Ablative therapy for people with localised prostate cancer: a systematic review and economic evaluation.

BACKGROUND For people with localised prostate cancer, active treatments are effective but have significant side effects. Minimally invasive treatments that destroy (or ablate) either the entire gland or the part of the prostate with cancer may be as effective and cause less side effects at an acceptable cost. Such therapies include cryotherapy, high-intensity focused ultrasound (HIFU) and brachytherapy, among others. OBJECTIVES This study aimed to determine the relative clinical effectiveness and cost-effectiveness of ablative therapies compared with radical prostatectomy (RP), external beam radiotherapy (EBRT) and active surveillance (AS) for primary treatment of localised prostate cancer, and compared with RP for salvage treatment of localised prostate cancer which has recurred after initial treatment with EBRT. DATA SOURCES MEDLINE (1946 to March week 3, 2013), MEDLINE In-Process & Other Non-Indexed Citations (29 March 2013), EMBASE (1974 to week 13, 2013), Bioscience Information Service (BIOSIS) (1956 to 1 April 2013), Science Citation Index (1970 to 1 April 2013), Cochrane Central Register of Controlled Trials (CENTRAL) (issue 3, 2013), Cochrane Database of Systematic Reviews (CDSR) (issue 3, 2013), Database of Abstracts of Reviews of Effects (DARE) (inception to March 2013) and Health Technology Assessment (HTA) (inception to March 2013) databases were searched. Costs were obtained from NHS sources. REVIEW METHODS Evidence was drawn from randomised controlled trials (RCTs) and non-RCTs, and from case series for the ablative procedures only, in people with localised prostate cancer. For primary therapy, the ablative therapies were cryotherapy, HIFU, brachytherapy and other ablative therapies. The comparators were AS, RP and EBRT. For salvage therapy, the ablative therapies were cryotherapy and HIFU. The comparator was RP. Outcomes were cancer related, adverse effects (functional and procedural) and quality of life. Two reviewers extracted data and carried out quality assessment. Meta-analysis used a Bayesian indirect mixed-treatment comparison. Data were incorporated into an individual simulation Markov model to estimate cost-effectiveness. RESULTS The searches identified 121 studies for inclusion in the review of patients undergoing primary treatment and nine studies for the review of salvage treatment. Cryotherapy [3995 patients; 14 case series, 1 RCT and 4 non-randomised comparative studies (NRCSs)], HIFU (4000 patients; 20 case series, 1 NRCS) and brachytherapy (26,129 patients; 2 RCTs, 38 NRCSs) studies provided limited data for meta-analyses. All studies were considered at high risk of bias. There was no robust evidence that mortality (4-year survival 93% for cryotherapy, 99% for HIFU, 91% for EBRT) or other cancer-specific outcomes differed between treatments. For functional and quality-of-life outcomes, the paucity of data prevented any definitive conclusions from being made, although data on incontinence rates and erectile dysfunction for all ablative procedures were generally numerically lower than for non-ablative procedures. The safety profiles were comparable with existing treatments. Studies reporting the use of focal cryotherapy suggested that incontinence rates may be better than for whole-gland treatment. Data on AS, salvage treatment and other ablative therapies were too limited. The cost-effectiveness analysis confirmed the uncertainty from the clinical review and that there is no technology which appears superior, on the basis of current evidence, in terms of average cost-effectiveness. The probabilistic sensitivity analyses suggest that a number of ablative techniques are worthy of further research. LIMITATIONS The main limitations were the quantity and quality of the data available on cancer-related outcomes and dysfunction. CONCLUSIONS The findings indicate that there is insufficient evidence to form any clear recommendations on the use of ablative therapies in order to influence current clinical practice. Research efforts in the use of ablative therapies in the management of prostate cancer should now be concentrated on the performance of RCTs and the generation of standardised outcomes. STUDY REGISTRATION This study is registered as PROSPERO CRD42012002461. FUNDING The National Institute for Health Research Health Technology Assessment programme.

Systematic Review of Adrenalectomy and Lymph Node Dissection in Locally Advanced Renal Cell Carcinoma

CONTEXT Controversy remains over whether adrenalectomy and lymph node dissection (LND) should be performed concomitantly with radical nephrectomy (RN) for locally advanced renal cell carcinoma (RCC) cT3-T4N0M0. OBJECTIVE To systematically review all relevant literature comparing oncologic, perioperative, and quality-of-life (QoL) outcomes for locally advanced RCC managed with RN with or without concomitant adrenalectomy or LND. EVIDENCE ACQUISITION Relevant databases were searched up to August 2012. Randomised controlled trials (RCTs) and comparative studies were included. Outcome measures were overall survival, QoL, and perioperative adverse effects. Risks of bias (RoB) were assessed using Cochrane RoB tools. Quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation approach. EVIDENCE SYNTHESIS A total of 3658 abstracts and 252 full-text articles were screened. Eight studies met the inclusion criteria: six LNDs (one RCT and five nonrandomised studies [NRSs]) and two adrenalectomies (two NRSs). RoB was high across the evidence base, and the quality of evidence from outcomes ranged from moderate to very low. Meta-analyses were not undertaken because of diverse study designs and data heterogeneity. There was no significant difference in survival between the groups, even though 5-yr overall survival appears better for the RN plus LND group compared with the no-LND group in one randomised study. There was no evidence of a difference in adverse events between the RN plus LND and no-LND groups. No studies reported QoL outcomes. There was no evidence of an oncologic difference between the RN with adrenalectomy and RN without adrenalectomy groups. No studies reported adverse events or QoL outcomes. CONCLUSIONS There is insufficient evidence to draw any conclusions on oncologic outcomes for patients having concomitant LND or ipsilateral adrenalectomy compared with patients having RN alone for cT3-T4N0M0 RCC. The quality of evidence is generally low and the results potentially biased. Further research in adequately powered trials is needed to answer these questions.

A core outcome set for localised prostate cancer effectiveness trials: protocol for a systematic review of the literature and stakeholder involvement through interviews and a Delphi survey

BackgroundProstate cancer is a growing health problem worldwide. The management of localised prostate cancer is controversial. It is unclear which of several surgical, radiotherapeutic, ablative, and surveillance treatments is the most effective. All have cost, process and recovery, and morbidity implications which add to treatment decision-making complexity for patients and healthcare professionals. Evidence from randomised controlled trials (RCTs) is not optimal because of uncertainty as to what constitutes important outcomes. Another issue hampering evidence synthesis is heterogeneity of outcome definition, measurement, and reporting. This project aims to determine which outcomes are the most important to patients and healthcare professionals, and use these findings to recommend a standardised core outcome set for comparative effectiveness trials of treatments for localised prostate cancer, to optimise decision-making.Methods/DesignThe range of potentially important outcomes and measures will be identified through systematic reviews of the literature and semi-structured interviews with patients. A consultation exercise involving representatives from two key stakeholder groups (patients and healthcare professionals) will ratify the list of outcomes to be entered into a three round Delphi study. The Delphi process will refine and prioritise the list of identified outcomes. A methodological substudy (nested RCT design) will also be undertaken. Participants will be randomised after round one of the Delphi study to one of three feedback groups, based on different feedback strategies, in order to explore the potential impact of feedback strategies on participant responses. This may assist the design of a future core outcome set and Delphi studies. Following the Delphi study, a final consensus meeting attended by representatives from both stakeholder groups will determine the final recommended core outcome set.DiscussionThis study will inform clinical practice and future trials of interventions of localised prostate cancer by standardising a core outcome set which should be considered in comparative effectiveness studies for localised prostate cancer.

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.

Determining information for inclusion in a decision-support intervention for clinical trial participation: a modified Delphi approach.

Background The use of decision-support interventions in the context of decisions about trial participation is an emergent field. There is a lack of evidence about what information is deemed important to support decisions about informed consent for clinical trials, and whether different groups agree on the information for inclusion. Purpose The overall objective was to determine the items which different stakeholder groups viewed to be important for inclusion in a decision-support tool when making decisions about clinical trial participation, with a view to use these as a framework for developing decision-support tools in this context. This is the first study to have addressed this issue. Methods A modified Delphi method was used to determine agreement on importance of items. The ‘stakeholder’ panel was made up of 49 individuals from 5 groups: 11 trialists, 6 research nurses, 7 ethics committee chairs, 9 decision-support experts, and 16 patients (9 trial experienced and 7 trial non-experienced). Two rounds of rating were completed. Items with a median of 7–10 with ≥65% of any one group (from aggregate ratings) in agreement were considered important for inclusion. Results The stakeholder panel achieved consensus on the majority of items included (60/66), agreeing that these were important for inclusion in a decision-support tool for trial participation. These included items covering information about trial participation and standard care, information on the likelihood of receiving different treatments, information to help patients determine what matters most to them, ensuring that the information is balanced, guidance on how to make a decision, disclosure of any conflicts of interest, using plain language in the tool, and guidance on the decision-support development process. Some areas of divergence among the panel were also identified relating to the use of patient stories. Limitations Selection bias may be a limitation in this study due to the manner in which the participants were invited to take part, and therefore, the representativeness, and reproducibility with another group of stakeholders, may differ. Conclusions Agreement was obtained on a number of items, which we recommend should be used as a framework to develop useful tools to support decision-making about participation in clinical trials.

Antiphospholipid (Hughes) syndrome: description of population and health-related quality of life (HRQoL) using the SF-36.

Objective Antiphospholipid (Hughes) syndrome (APS) affects mainly women 15 to 50 years of age and is responsible for approximately 20% of strokes in people <40 years. Little is known about the psychological burden of this long-term condition. We investigated HRQoL in APS. Methods We conducted a cross-sectional survey involving 270 members of the Hughes Syndrome Foundation worldwide. Data included HRQoL (SF-36), demographics, and APS-related self-reported major issues. Response rate was 60%. Results T-tests indicated significantly worse mean scores for seven of the eight domains of the SF-36 in secondary antiphospholipid syndrome (SAPS) compared to primary antiphospholipid syndrome (PAPS), e.g. bodily pain t(263) = 6.10 p < 0.001 except for mental health t(267) = 1.95 p = 0.053. PAPS appeared to be associated with poorer HRQoL in most mental health domains but overall better physical domains compared to systemic lupus erythematosus (SLE) alone. SAPS appeared to have a more adverse impact on HRQoL compared to PAPS and SLE. Major issues identified: pain and fatigue, lack of health care professional/public awareness, and medication unpredictability. Conclusion HRQoL in PAPS appears to be generally better than SLE and SAPS in physical domains, but poorer in mental domains. APS patients might need more social support in terms of information and awareness of the condition to improve their coping strategies.

Patient-centered Care in Maternity Services: A Critical Appraisal and Synthesis of the Literature

BACKGROUND Patient-centered care (PCC) has been recognized as a marker of quality in health service delivery. In policy documents, PCC is often used interchangeably with other models of care. There is a wide literature about PCC, but there is a lack of evidence about which model is the most appropriate for maternity services specifically. AIM We sought to identify and critically appraise the literature to identify which definition of PCC is most relevant for maternity services. METHODS The four-step approach used to identify definitions of PCC was to 1) search electronic databases using key terms (1995-2011), 2) cross-reference key papers, 3) search of specific journals, and 4) search the grey literature. Four papers and two books met our inclusion criteria. ANALYSIS A four-criteria critical appraisal tool developed for the review was used to appraise the papers and books. MAIN RESULTS From the six identified definitions, the Shallers definition met the majority of the four criteria outlined and seems to be the most relevant to maternity services because it includes physiologic conditions as well as pathology, psychological aspects, a nonmedical approach to care, the greater involvement of family and friends, and strategies to implement PCC. CONCLUSION This review highlights Shallers definitions of PCC as the one that would be the most inclusive of all women using maternity services. Future research should concentrate on evaluating programs that support PCC in maternity services, and testing/validating this model of care.

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