Molly M. Neuberger

Screening for prostate cancer: systematic review and meta-analysis of randomised controlled trials

Objective To examine the evidence on the benefits and harms of screening for prostate cancer. Design Systematic review and meta-analysis of randomised controlled trials. Data sources Electronic databases including Medline, Embase, CENTRAL, abstract proceedings, and reference lists up to July 2010. Review methods Included studies were randomised controlled trials comparing screening by prostate specific antigen with or without digital rectal examination versus no screening. Data abstraction and assessment of methodological quality with the GRADE approach was assessed by two independent reviewers and verified by the primary investigator. Mantel-Haenszel and inverse variance estimates were calculated and pooled under a random effects model expressing data as relative risks and 95% confidence intervals. Results Six randomised controlled trials with a total of 387 286 participants that met inclusion criteria were analysed. Screening was associated with an increased probability of receiving a diagnosis of prostate cancer (relative risk 1.46, 95% confidence interval 1.21 to 1.77; P<0.001) and stage I prostate cancer (1.95, 1.22 to 3.13; P=0.005). There was no significant effect of screening on death from prostate cancer (0.88, 0.71 to 1.09; P=0.25) or overall mortality (0.99, 0.97 to 1.01; P=0.44). All trials had one or more substantial methodological limitations. None provided data on the effects of screening on participants’ quality of life. Little information was provided about potential harms associated with screening. Conclusions The existing evidence from randomised controlled trials does not support the routine use of screening for prostate cancer with prostate specific antigen with or without digital rectal examination.

Circulating and tumor-infiltrating myeloid cell subsets in patients with bladder cancer

Both cancer‐related inflammation and tumor‐induced immune suppression are associated with expansion of myeloid cell subsets including myeloid‐derived suppressor cells. However, little known regarding characteristics of myeloid cells in patients with bladder cancer. In this study, we analyzed myeloid cells from peripheral blood (PBMC) and tumor tissue that were collected from patients with superficial noninvasive and invasive urothelial carcinomas. Our results demonstrate that PBMC from bladder cancer patients contain two major CD11b myeloid cell subsets: granulocyte‐type CD15high CD33low cells and monocyte‐type CD15low CD33high cells. The number of circulating granulocytic but not monocytic myeloid cells in cancer patients was markedly increased when compared to healthy individuals. Both myeloid cell subsets from cancer patients were highly activated and produced substantial amounts of proinflammatory chemokines/cytokines including CCL2, CCL3, CCL4, G‐CSF, IL‐8 and IL‐6. Granulocytic myeloid cells were able to inhibit in vitro T cell proliferation through induction of CD4+Foxp3+ T regulatory cells. Analysis of bladder cancer tissues revealed that tumors were infiltrated with monocyte–macrophage CD11b+HLA‐DR+ and granulocytic CD11b+CD15+HLA‐DR‐ myeloid cells. Collectively, this study identifies myeloid cell subsets in patients with bladder cancer. We demonstrate that these highly activated inflammatory myeloid cells represent a source of multiple chemokines/cytokines and may contribute to inflammation and immune dysfunction in bladder cancer.

The Impact of the Extent of Lymphadenectomy on Oncologic Outcomes in Patients Undergoing Radical Cystectomy for Bladder Cancer: A Systematic Review

CONTEXT Controversy exists regarding the therapeutic value of lymphadenectomy (LND) in patients undergoing radical cystectomy (RC) for muscle-invasive bladder cancer (MIBC). OBJECTIVE To systematically review the relevant literature assessing the impact of LND on oncologic and perioperative outcomes in patients undergoing RC for MIBC. EVIDENCE ACQUISITION Medline, Medline In-Process, Embase, the Cochrane Central Register of Controlled Trials, and the Latin American and Caribbean Center on Health Sciences Information (LILACS) were searched up to December 2013. Comparative studies reporting on no LND, limited LND (L-LND), standard LND (S-LND), extended LND (E-LND), superextended LND (SE-LND), and oncologic and perioperative outcomes were included. Risk-of-bias and confounding assessments were performed. EVIDENCE SYNTHESIS Twenty-three studies reporting on 19,793 patients were included. All but one study were retrospective. Planned meta-analyses were not possible because of study heterogeneity; therefore, data were synthesized narratively. There were high risks of bias and confounding across most studies as well as extreme heterogeneity in the definition of the anatomic boundaries of LND templates. All seven studies comparing LND with no LND favored LND in terms of better oncologic outcomes. Seven of 14 studies comparing (super)extended LND with L-LND or S-LND reported a beneficial outcome for (super)extended LND in at least a subset of patients. No difference in outcome was reported in two studies comparing E-LND and S-LND. The comparative harms of different extents of LND remain unclear. CONCLUSIONS Although the quality of the data was poor, the available evidence indicates that any kind of LND is advantageous over no LND. Similarly, E-LND appears to be superior to lesser degrees of dissection, while SE-LND offered no additional benefits. It is hoped that data from ongoing randomized clinical trials will clarify remaining uncertainties. PATIENT SUMMARY The current literature suggests that removal of lymph nodes in bladder cancer surgery is beneficial and might result in better outcomes in terms of prolonging survival; however, the quality of the available studies is poor, and high-quality studies are needed.

Predictors of citations in the urological literature

Whats known on the subject? and What does the study add?

Clinical Practice Guidelines on Prostate Cancer: A Critical Appraisal

PURPOSE Clinical practice guidelines are increasingly being used by leading organizations to promote high quality evidence-based patient care. However, the methodological quality of clinical practice guidelines developed by different organizations varies considerably. We assessed published clinical practice guidelines on the treatment of localized prostate cancer to evaluate the rigor, applicability and transparency of their recommendations. MATERIALS AND METHODS We searched for English based clinical practice guidelines on treatment of localized prostate cancer from leading organizations in the 15-year period from 1999 to 2014. Clinical practice guidelines limited to early detection, screening, staging and/or diagnosis of prostate cancer were excluded from analysis. Four independent reviewers used the validated AGREE II instrument to assess the quality of clinical practice guidelines in 6 domains, including 1) scope and purpose, 2) stakeholder involvement, 3) rigor of development, 4) clarity of presentation, 5) applicability and 6) editorial independence. RESULTS A total of 13 clinical practice guidelines met inclusion criteria. Overall the highest median scores were in the AGREE II domains of clarity of presentation, editorial independence, and scope and purpose. The lowest median score was for applicability (28.1%). Although the median score of editorial independence was high (85.4%), variability was also substantial (IQR 12.5-100). NICE and AUA clinical practice guidelines consistently scored well in most domains. CONCLUSIONS Clinical practice guidelines from different organizations on treatment of localized prostate cancer are of variable quality and fall short of current standards in certain areas, especially in applicability and stakeholder involvement. Improvements in these key domains can enhance the impact and implementation of clinical practice guidelines.

A Systematic Review of the Quality of Evidence of Ablative Therapy for Small Renal Masses

PURPOSE We critically assessed the methodological and reporting quality of published studies of ablative techniques for small renal masses. MATERIALS AND METHODS We performed a systematic PubMed® and EMBASE® literature search from January 1966 to March 2010 to identify all full text, original research publications on ablative therapy for renal masses. Six reviewers working independently in 3 teams performed duplicate data abstraction using Strengthening the Reporting of Observational Studies in Epidemiology criteria, which were pilot tested in a separate sample. RESULTS A total of 117 original research publications published in a 15-year period (1995 to 2009) met eligibility criteria. No randomized, controlled trials were identified. All studies were observational and 88.9% had 1 arm with no comparison group. Median sample size was 18 patients (IQR 5.5, 40.0) and 53.8% of studies included 20 or fewer patients. Median followup was 14.0 months (IQR 8.0, 23.8) and only 19.7% of studies had an average followup of greater than 24 months. Of the studies 20.5% mentioned the number of operators involved and only 6.0% provided information on their experience level. Of the studies 66.7% addressed the recurrence rate. Disease specific and overall survival was reported in only 15.4% and 16.2% of studies, respectively. CONCLUSIONS The published literature on the therapeutic efficacy of ablative therapy for renal masses is largely limited to uncontrolled, 1-arm observational studies. In the absence of higher quality evidence ablative therapy outside research studies should be limited to select patients who are not candidates for surgical intervention.

Psychosocial interventions for men with prostate cancer: A Cochrane systematic review

To evaluate the effectiveness of psychosocial interventions for men with prostate cancer in improving quality of life (QoL), self‐efficacy and knowledge and in reducing distress, uncertainty and depression. We searched for trials using a range of electronic databases including the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and PsycINFO to October 2013, together with hand searching of journals and reference lists. Randomised controlled trials were eligible if they included psychosocial interventions that explicitly used one or a combination of the following approaches: cognitive behavioural, psycho‐educational, supportive and counselling. Interventions had to be delivered or facilitated by trained or lay personnel. Our outcomes were an improvement in QoL, self‐efficacy and knowledge and a reduction in distress, uncertainty and depression. Pairs of review authors independently extracted data and assessed risk of bias. We analysed data using standardised mean differences (SMDs), random‐effects models and 95% confidence intervals (CIs). In all, 19 studies with a total of 3 204 men, with a diagnosis of prostate cancer, comparing psychosocial interventions vs usual care were included in this review. Men in the psychosocial intervention group had a small, statistically significant improvement in the physical component of general health‐related QoL (GHQoL) at end of intervention (SMD 0.12, 95% CI 0.01–0.22) based on low quality evidence. There was no clear evidence of benefit associated with psychosocial interventions for the mental component of GHQoL at end of intervention (SMD −0.04, 95% CI −0.15 to 0.06) based on moderate quality evidence. At end of intervention, cancer‐related QoL showed a small improvement after psychosocial interventions (SMD 0.21, 95% CI 0.04–0.39). For prostate cancer‐specific and symptom‐related QoL, the differences between intervention and control groups were not significant. There was no clear evidence that psychosocial interventions were beneficial in improving self‐efficacy at end of intervention (SMD 0.16, 95% CI −0.05 to 0.38) based on very low quality evidence. Men in the psychosocial intervention group had a moderate increase in prostate cancer knowledge at end of intervention (SMD 0.51, 95% CI 0.32–0.71) based on very low quality evidence. A small increase in knowledge with psychosocial interventions was noted at 3 months after intervention (SMD 0.31, 95% CI 0.04–0.58). The results for uncertainty (SMD −0.05, 95% CI −0.35 to 0.26) and distress (SMD 0.02, 95% CI −0.11 to 0.15) at end of intervention were compatible with both benefit and harm based on very low quality evidence. Finally, there was no clear evidence of benefit associated with psychosocial interventions for depression at end of intervention (SMD −0.18, 95% CI −0.51 to 0.15) based on very low quality evidence. The overall risk of bias in the included studies was unclear or high, primarily as the result of performance bias. No data about stage of disease or treatment with androgen‐deprivation therapy were extractable for subgroup analysis. Only one study addressed adverse effects. Overall, this review shows that psychosocial interventions may have small, short‐term beneficial effects on certain domains of wellbeing, as measured by the physical component of GHQoL and cancer‐related QoL when compared with usual care. Prostate cancer knowledge was also increased. However, this review failed to show a statistically significant effect on other domains such as symptom‐related QoL, self‐efficacy, uncertainty, distress or depression. Moreover, when beneficial effects were seen, it remained uncertain whether the magnitude of effect was large enough to be considered clinically important. The quality of evidence for most outcomes was rated as very low according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system, reflecting study limitations, loss to follow‐up, study heterogeneity and small sample sizes. We were unable to perform meaningful subgroup analyses based on disease stage or treatment method. Although some findings of this review are encouraging, they do not provide sufficiently strong evidence to permit meaningful conclusions about the effects of these interventions in men with prostate cancer. Additional well executed and transparently reported research studies are necessary to establish the role of psychosocial interventions in men with prostate cancer.

Low Methodological and Reporting Quality of Randomized, Controlled Trials of Devices to Treat Urolithiasis

PURPOSE We assessed the methodological and reporting quality of randomized, controlled trials of stone disease management and determined whether the reporting quality of randomized, controlled trials improved with time. MATERIALS AND METHODS We systematically searched the literature for randomized, controlled trials of urolithiasis treatment. We developed and pilot tested a data extraction checklist based on CONSORT (Consolidated Standards of Reporting Trials) criteria as well as a clinical checklist relevant to urolithiasis, each scored as 0 to 25. Our primary outcome measures were the mean differences in CONSORT and clinical summary scores with time. We performed statistical hypothesis testing using the Student t-test with 2-sided α = 0.05 to compare scores between 2002 to 2006 and 2007 to 2011. RESULTS A total of 104 randomized, controlled trials met study inclusion criteria. The most common procedure types studied were percutaneous nephrolithotomy (41.3%), ureteral stenting (28.8%) and shock wave lithotripsy (25.0%). Mean ± SE CONSORT summary scores were 11.4 ± 0.4 and 12.1 ± 0.3 in 2002 to 2006 and 2007 to 2011, respectively, with a mean difference of 0.7 (95% CI -0.3-1.6, p = 0.167). Mean clinical summary scores were 7.4 ± 0.5 and 9.3 ± 0.4 in 2002 to 2006 and 2007 to 2011, respectively, with a mean difference of 1.8 (95% CI 0.6-3.1, p = 0.004). CONCLUSIONS While the number of randomized, controlled trials of urological devices used to treat stone disease substantially increased with time, methodological and clinical reporting quality remains suboptimal. This compromises their credibility and warrants efforts to promote appropriate performance of future endourological studies.

Tumour-seeding: a rare complication of ablative therapy for clinically localised renal cell carcinoma

Current evidence-based clinical practice guidelines identify surgical resection as the recommended treatment of small renal masses. Ablative approaches such as laparoscopic and percutaneous cryoablation and radiofrequency ablation offer the promise of complete tumour destruction by a less-invasive approach with regard to outcomes such as anaesthesia requirements, blood loss, length of stay and time to recovery, making them appealing to patients. However, evidence of therapeutic benefits, harms and costs for these methods remains limited. We report a case of applicator tract seeding by tumour following percutaneous cryoablation of renal cell carcinoma; a rare and potentially under-reported, yet catastrophic complication of ablative therapy.

Diagnostic tests in urology: percentage of free prostate-specific antigen (PSA).

Free to total PSA ratios are commonly used as an adjunct to total PSA levels to better define an individuals risk for prostate cancer; however, its strengths and weaknesses are not well understood. This article illustrates the use of likelihood ratios that can be generated from the reported sensitivities and specificities from given free to total PSA thresholds in either increasing or decreasing an individual patients probability of prostate cancer. Understanding the strengths and limitations of free to total PSA testing will help clinicians anticipate whether its use is indicated or not.