T.R. Leyshon Griffiths

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 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.

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.

The role of hexylaminolaevulinate in the diagnosis and follow-up of non-muscle-invasive bladder cancer

Barnet and Chase Farm Hospitals NHS Trust, Herts, *Frimley Park Hospital, Camberley, Surrey, † University Hospitals of Leicester NHS Trust, Department of Urology, Clinical Sciences Unit, Leicester General Hospital, †† Renal and Urology Services, Haemodialysis Unit, Leicester General Hospital, Leicester, ‡ Basingstoke and North Hampshire Hospital, Basingstoke, § University College London, Division of Surgery and Interventional Science, London, and ¶ University Hospitals Bristol NHS Foundation Trust, Bristol, UK

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

Is the role of intravesical bacillus Calmette‐Guérin in non‐muscle‐invasive bladder cancer changing?

Intravesical BCG is recommended as adjuvant therapy for intermediate-risk and high-risk non-muscle-invasive bladder cancer (NMIBC) in guidelines from the European Association of Urology (EAU), the AUA, the BAUS working in association with the British Uro-oncology Group and the National Comprehensive Cancer Network [1–4]. Meta-analyses show Level 1a evidence that BCG reduces recurrence and progression rates, in a disease where the 5-year probability of recurrence is up to 62% (intermediate-risk NMIBC) and 78% (high-risk NMIBC), and the 5-year probability of progression is up to 6% and 45%, respectively [5]. Despite this evidence, there are still questions over the use of intravesical BCG. Is maintenance therapy required? What is the optimal dose and schedule? Is BCG superior to intravesical chemotherapy in intermediate-risk NMIBC? Will BCG be challenged by device-assisted chemotherapy? In addition, a reduction in disease progression is not universally reported. In this article we explore the data surrounding intravesical BCG and will discuss the areas that remain under debate.

Radiofrequency-induced Thermo-chemotherapy Effect Versus a Second Course of Bacillus Calmette-Guérin or Institutional Standard in Patients with Recurrence of Non–muscle-invasive Bladder Cancer Following Induction or Maintenance Bacillus Calmette-Guérin Therapy (HYMN): A Phase III, Open-label, Randomised Controlled Trial

BACKGROUND There is no effective intravesical second-line therapy for non-muscle-invasive bladder cancer (NMIBC) when bacillus Calmette-Guérin (BCG) fails. OBJECTIVE To compare disease-free survival time (DFS) between radiofrequency-induced thermo-chemotherapy effect (RITE) and institutional standard second-line therapy (control) in NMIBC patients with recurrence following induction/maintenance BCG. DESIGN, SETTINGS, AND PARTICIPANTS Open-label, phase III randomised controlled trial accrued across 14 centres between May 2010 and July 2013 (HYMN [ClinicalTrials.gov: NCT01094964]). INTERVENTION Patients were randomly assigned (1:1) to RITE (60min, 40mg mitomycin-C, 42±2°C) or control following stratification for carcinoma in situ (CIS) status (present/absent), therapy history (failure of previous induction/maintenance BCG), and treatment centre. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Primary outcome measures were DFS and complete response (CR) at 3 mo for the CIS at randomisation subgroup. Analysis was based on intention-to-treat. RESULTS AND LIMITATIONS A total of 104 patients were randomised (48 RITE: 56 control). Median follow-up for the 31 patients without a DFS event was 36 mo. There was no significant difference in DFS between treatment arms (hazard ratio [HR] 1.33, 95% confidence interval [CI] 0.84-2.10, p=0.23) or in 3-mo CR rate in CIS patients (n=71; RITE: 30% vs control: 47%, p=0.15). There was no significant difference in DFS between treatment arms in non-CIS patients (n=33; RITE: 53% vs control: 24% at 24 mo, HR 0.50, 95% CI 0.22-1.17, p=0.11). DFS was significantly lower in RITE than in control in CIS with/without papillary patients (n=71; HR 2.06, 95% CI 1.17-3.62, p=0.01; treatment-subgroup interaction p=0.007). Disease progression was observed in four patients in each treatment arm. Adverse events and health-related quality of life between treatment arms were comparable. CONCLUSIONS DFS was similar between RITE and control. RITE may be a second-line therapy for non-CIS recurrence following BCG failure; however, confirmatory trials are needed. RITE patients with CIS with/without papillary had lower DFS than control. HYMN highlights the importance of the control arm when evaluating novel therapies. PATIENT SUMMARY This study did not show a difference in bladder cancer outcomes between microwave-heated chemotherapy and standard of care treatment. Papillary bladder lesions may benefit from microwave-heated chemotherapy treatment; however, more research is needed. Both treatments are similarly well tolerated.

Is the role of intravesical bacillus Calmette-Guérin in non-muscle-invasive bladder cancer changing?: ROLE OF INTRAVESICAL BCG IN NON-MUSCLE-INVASIVE BLADDER CANCER

Intravesical BCG is recommended as adjuvant therapy for intermediate-risk and high-risk non-muscle-invasive bladder cancer (NMIBC) in guidelines from the European Association of Urology (EAU), the AUA, the BAUS working in association with the British Uro-oncology Group and the National Comprehensive Cancer Network [1–4]. Meta-analyses show Level 1a evidence that BCG reduces recurrence and progression rates, in a disease where the 5-year probability of recurrence is up to 62% (intermediate-risk NMIBC) and 78% (high-risk NMIBC), and the 5-year probability of progression is up to 6% and 45%, respectively [5]. Despite this evidence, there are still questions over the use of intravesical BCG. Is maintenance therapy required? What is the optimal dose and schedule? Is BCG superior to intravesical chemotherapy in intermediate-risk NMIBC? Will BCG be challenged by device-assisted chemotherapy? In addition, a reduction in disease progression is not universally reported. In this article we explore the data surrounding intravesical BCG and will discuss the areas that remain under debate.

The role of hexylaminolaevulinate in the diagnosis and follow-up of non-muscle-invasive bladder cancer: HEXYLAMINOLAEVULINATE AND THE DIAGNOSIS AND FOLLOW-UP OF NMIBC

Barnet and Chase Farm Hospitals NHS Trust, Herts, *Frimley Park Hospital, Camberley, Surrey, † University Hospitals of Leicester NHS Trust, Department of Urology, Clinical Sciences Unit, Leicester General Hospital, †† Renal and Urology Services, Haemodialysis Unit, Leicester General Hospital, Leicester, ‡ Basingstoke and North Hampshire Hospital, Basingstoke, § University College London, Division of Surgery and Interventional Science, London, and ¶ University Hospitals Bristol NHS Foundation Trust, Bristol, UK