Steven 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.

Systematic Review and Meta-analysis of the Clinical Effectiveness of Shock Wave Lithotripsy, Retrograde Intrarenal Surgery, and Percutaneous Nephrolithotomy for Lower-pole Renal Stones

UNLABELLED The prevalence of urolithiasis is increasing. Lower-pole stones (LPS) are the most common renal calculi and the most likely to require treatment. A systematic review comparing shock wave lithotripsy (SWL), retrograde intrarenal surgery (RIRS), and percutaneous nephrolithotomy (PNL) in the treatment of ≤20 mm LPS in adults was performed. Comprehensive searches revealed 2741 records; 7 randomised controlled trials (RCTs) recruiting 691 patients were included. Meta-analyses for stone-free rate (SFR) at ≤3 mo favoured PNL over SWL (risk ratio [RR]: 2.04; 95% confidence interval [CI], 1.50-2.77) and RIRS over SWL (RR: 1.31; 95% CI, 1.08-1.59). Stone size subgroup analyses revealed PNL and RIRS were considerably more effective than SWL for >10 mm stones, but the magnitude of benefit was markedly less for ≤10 mm stones. The quality of evidence (Grading of Recommendations Assessment, Development, and Evaluation [GRADE]) for SFR was moderate for these comparisons. The median SFR from reported RCTs suggests PNL is more effective than RIRS. The findings regarding other outcomes were inconclusive because of limited and inconsistent data. Well-designed, prospective, comparative studies that measure these outcomes using standardised definitions are required, particularly for the direct comparison of PNL and RIRS. This systematic review, which used Cochrane methodology and GRADE quality-of-evidence assessment, provides the first level 1a evidence for the management of LPS. PATIENT SUMMARY We thoroughly examined the literature to compare the benefits and harms of the different ways of treating kidney stones located at the lower pole. PNL and RIRS were superior to SWL in clearing the stones within 3 mo, but we were unable to make any conclusions regarding other outcomes. More data is required from reliable studies before firm recommendations can be made.

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.

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.

Role of Hormonal Treatment in Prostate Cancer Patients with Nonmetastatic Disease Recurrence After Local Curative Treatment: A Systematic Review

CONTEXT The relative benefits and harms of hormonal treatment (HT) versus no or deferred HT in patients with nonmetastatic prostate cancer (PCa) relapse after primary curative therapy are controversial. OBJECTIVE To assess the effectiveness of HT for nonmetastatic PCa relapse, prognostic factors for treatment outcome, timing of treatment, and the most effective treatment strategy to provide guidance for clinical practice. EVIDENCE ACQUISITION A systematic literature search was undertaken incorporating Medline, Embase, and the Cochrane Library (search ended March 2015). Studies were critically appraised for risk of bias. The outcomes included overall and cancer-specific survival, metastasis-free survival, symptom-free survival, progression to castrate resistance, adverse events, and quality of life. EVIDENCE SYNTHESIS Of 9687 articles identified, 27 studies were eligible for inclusion (2 RCTs, 8 nonrandomised comparative studies, and 17 case series). The results suggest that only a subgroup of patients, especially those with high-risk disease, may benefit from early HT. The main predictors for unfavourable outcomes were shorter PSA doubling time (<6-12 mo) and higher Gleason score (>7). Early HT may be warranted for patients with high-risk disease. An intermittent HT strategy appears feasible. Most studies had a moderate to high risks of bias. CONCLUSIONS HT for PCa relapse after primary therapy with curative intent should be reserved for patients at highest risk of progression and with a long life expectancy. The potential benefits of starting HT should be judiciously balanced against the associated harms. PATIENT SUMMARY This article summarises the evidence on the benefits and harms of hormonal treatment in prostate cancer (PCa) patients in whom the disease has recurred following earlier curative treatment. We found that only a select group of patients with aggressive PCa and a fast rising prostate-specific antigen may benefit from early hormonal treatment (HT), whereas in others HT may be more harmful than beneficial.

Sentinel Node Procedure in Prostate Cancer: A Systematic Review to Assess Diagnostic Accuracy

CONTEXT Extended pelvic lymph node dissection (ePLND) is the gold standard for detecting lymph node (LN) metastases in prostate cancer (PCa). The benefit of sentinel node biopsy (SNB), which is the first draining LN as assessed by imaging of locally injected tracers, remains controversial. OBJECTIVE To assess the diagnostic accuracy of SNB in PCa. EVIDENCE ACQUISITION A systematic literature search of Medline, Embase, and the Cochrane Library (1999-2016) was undertaken using PRISMA guidelines. All studies of SNB in men with PCa using PLND as reference standard were included. The primary outcomes were the nondiagnostic rate (NDR), sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and false positive (FP) and false negative (FN) rates. Relevant sensitivity analyses based on SN definitions, ePLND as reference standard, and disease risk were undertaken, including a risk of bias (RoB) assessment. EVIDENCE SYNTHESIS Of 373 articles identified, 21 studies recruiting a total of 2509 patients were eligible for inclusion. Median cumulative percentage (interquartile range) results were 4.1% (1.5-10.7%) for NDR, 95.2% (81.8-100%) for sensitivity, 100% (95.0-100%) for specificity, 100% (87.0-100%) for PPV, 98.0% (94.3-100%) for NPV, 0% (0-5.0%) for the FP rate, and 4.8% (0-18.2%) for the FN rate. The findings did not change significantly on sensitivity analyses. Most studies (17/22) had low RoB for index test and reference standard domains. CONCLUSIONS SNB appears to have diagnostic accuracy comparable to ePLND, with high sensitivity, specificity, PPV and NPV, and a low FN rate. With a low FP rate (rate of detecting positive nodes outside the ePLND template), SNB may not have any additional diagnostic value over and above ePLND, although SNB appears to increase nodal yield by increasing the number of affected nodes when combined with ePLND. Thus, in high-risk disease it may be prudent to combine ePLND with SNB. PATIENT SUMMARY This literature review showed a high diagnostic accuracy for sentinel node biopsy in detecting positive lymph nodes in prostate cancer, but further studies are needed to explore the effect of sentinel node biopsy on complications and oncologic outcome.

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.

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.