Vikram Narayan

The landscape of systematic reviews in urology (1998 to 2015): an assessment of methodological quality

To assess the quality of published systematic reviews in the urology literature (an extension of our previously reported work), as high‐quality systematic reviews play a paramount role in informing evidence‐based clinical practice.

Novel biomarkers for prostate cancer: An evidence-based review for use in clinical practice

Prostate cancer is a heterogeneous disease with disparate outcomes. Traditional clinical parameters are limited in their ability to differentiate between these cases, and there is uncertainty regarding management strategies. A number of novel biomarkers have emerged, but how best to use them at the point of care remains confusing. In the present review, we describe the most common novel biomarkers, their key supporting literature, and propose a meaningful algorithm for their use in clinical practice. To identify commercially available prostate cancer diagnostic tests, we carried out a PubMed literature search (through May 2016). Only English‐language studies were included. We restricted our search to studies published within the past 10 years in order to focus our review on novel data. Secondary sources were also examined. We identified 12 novel biomarkers and categorized them into broad areas of clinical practice: (i) early diagnosis and screening; (ii) staging and primary treatment selection; (iii) post‐treatment risk stratification; (iv) advanced disease prognosis and treatment response; and (v) emerging tests. Most validation studies rely on small retrospective cohorts and carry a high risk of bias; furthermore, most cohorts are restricted to Caucasians, with little to no representation of other geographic, racial or ethnic populations. Novel biomarkers for prostate cancer management, while potentially helpful, should not replace standard clinical information and physician judgment. They are currently best suited to serve as an adjunct to existing management tools. Clinicians should have a sound grasp of each biomarker‐based tests indications and limitations.

Improved Reporting of Randomized Controlled Trials in the Urologic Literature

BACKGROUND Well-designed randomized controlled trials (RCTs) have the potential to provide high-quality evidence to inform questions of therapy and prevention, but this potential is contingent on the use of appropriate methods and transparent reporting. OBJECTIVE To systematically assess the quality of urology RCT reporting and identify trends over time. DESIGN, SETTING, AND PARTICIPANTS All RCTs published in four leading urology journals in 2013 were identified and compared to a prior analysis of studies from 1996 and 2004. Two reviewers abstracted data based on the Consolidated Standards of Reporting Trials (CONSORT) checklist. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS A summary reporting score (range: 0-22) for each study was determined. Mean overall scores for 1996, 2004, and 2013 were compared using analysis of variance. We used χ2 to compare the reporting frequency of individual criteria. RESULTS AND LIMITATIONS Mean CONSORT scores for RCTs were 15.6±2.0 in 2013 (n=82), 12.0±0.3 in 2004 (n=87), and 10.2±0.3 in 1996 (n=65); p<0.01. Key deficiencies remain in reporting methods of allocation concealment and group assignment (selection bias), and blinding of participants, personnel, and outcome assessors (performance and detection bias). Study limitations are potential reviewer bias resulting from lack of journal deidentification and the relatively low number of studies reviewed. CONCLUSIONS There has been a substantial improvement in reporting quality of RCTs in urology since CONSORT. Some methodological criteria remain underreported, and increased efforts are necessary to further this improvement. PATIENT SUMMARY Treatment decisions are often based on data from randomized controlled trials. We looked at whether these trials in urology are transparent in reporting their design and conduct using a framework known as the CONSORT criteria and found significant improvements over time. Some areas of deficiency remain, and our paper aimed to highlight these drawbacks to promote continued high-quality research.

The Prevalence and Impact of Urinary Marker Testing in Patients with Bladder Cancer

Purpose Novel urinary tumor markers for bladder cancer may permit early detection and improved oncologic outcomes but data on use is limited. We sought to identify trends in the application of urinary markers and long‐term outcomes of urinary tumor marker use in patients with bladder cancer. Materials and Methods Data from the SEER (Surveillance, Epidemiology and End Results)‐Medicare database from 2001 to 2011 were used to identify a cohort of 64,450 patients with bladder cancer who underwent urinary marker testing with UroVysion® fluorescence in situ hybridization, or the NMP22® or BTA Stat® test. We assessed the prevalence of urinary marker testing and urine cytology. Characteristics of patients who did and did not undergo urinary marker testing were analyzed by the chi‐square test. Urinary marker testing predictors were analyzed with a multivariable logistic regression model and Cox proportional hazards were used to determine unadjusted cancer specific and overall mortality risks. Results The rate of urinary marker testing increased from 17.8% to a peak of 28.2% during the study years (p <0.0001). Predictors of marker use included female gender, younger age and lower Charlson score. Overall and cancer specific survival improved on Kaplan‐Meier and Cox proportional hazards analyses with urinary marker testing. Conclusions Increased urinary marker testing was documented over all stages and grades of bladder cancer, and in certain patient and provider variables. This increase may have contributed to improved overall and cancer specific survival. Additional investigation is necessary to further characterize this benefit.

The Effects of Population-based Prostate-specific Antigen Screening Beginning at Age 40

OBJECTIVE To evaluate population-based prostate cancer (CaP) testing of men in their 40s, given the paucity of prospective data evaluating the consequences of prostate-specific antigen (PSA) testing in younger men for CaP. MATERIALS AND METHODS A total of 1052 men in their 40s were followed longitudinally for prostate outcomes, from 1990 to 2010. A random subset of 268 men was selected to undergo biennial CaP testing including PSA testing, transrectal ultrasound, and a digital rectal examination. A representative population of 609 men with a subset of 159 men who also began CaP testing in their 50s was also evaluated as a comparison group. Risk of prostate biopsy (PBx), CaP, or death from CaP was compared between CaP-tested and the routine-care population cohort. RESULTS Median follow-up was 17.2 years. Men aged 40-49, who underwent CaP testing were 2.4 times more likely to undergo a PBx (hazard ratio [HR] 2.4 95% confidence interval [CI] 1.8-3.3) and 2.2 times more likely to be diagnosed with low-risk CaP (HR 2.2, 95% CI 1.12-4.0). Those initiating CaP testing a decade earlier were 2.2 times and 1.7 times more likely to be biopsied and be diagnosed with CaP for any given age (HR 2.2 95% CI 1.4-3.5 and 1.7 95% CI 1.1-2.7, respectively). CONCLUSION CaP testing in men beginning at age 40 resulted in a significant increase in the risk of PBx and diagnosis of low-risk CaP, without a measurable reduction in risk of CaP-death in this low-risk population. However, given the natural history of CaP, a longer follow-up is needed to confirm this finding.

Re: Richard J. Sylvester, Steven E. Canfield, Thomas B.L. Lam, et al. Conflict of Evidence: Resolving Discrepancies When Findings from Randomized Controlled Trials and Meta-analyses Disagree. Eur Urol 2017;71:811–9

The article by Sylvester and members of the European Association of Urology guidelines leadership team addresses the intriguing issue of conflicting evidence from individual, large, and well-designed randomized controlled trials (RCTs) on the one hand and systematic reviews (SRs) on the other [1]. While we agree with most of the statements made, we are concerned that some issues are not laid out as clearly as they could be. We therefore wish to highlight a few important take home messages. First, developers of evidence-based clinical practice guidelines are required to develop their recommendations on the basis of rigorous SRs of the entire body of evidence. This reflects a widely accepted principle of evidence-based medicine (EBM) and a mandate by the Institute of Medicine, now the National Academy of Medicine, in its publication Clinical Practice Guidelines We Can Trust [2]. Second, the phenomenon of conflicting results from different studies addressing the same clinical question is common and one that authors of rigorous SRs are well equipped to deal with through a priori planned subgroup analyses that seek to investigate the source of unexplained heterogeneity. It is noteworthy that the results of the SUSPEND trial on the value of medical expulsive therapy (MET) in patients with ureteral colic are not that different from the findings of 54 other trials addressing the same question when combined in a meta-analysis [3]. As derived from a predefined subgroup analysis, MET may in fact be beneficial in patients with large stones, an analysis that the SUSPEND trial was not designed or powered to adequately address [4]. Third, guidance exists as to when SR authors should look beyond evidence from RCTs alone. Rather than indiscriminately pooling across RCTs and observational studies, SR authors should first scrutinize the evidence from RCTs alone. If study limitations and other issues affecting the quality of evidence according to GRADE force them to lower the confidence in the estimates of effect for a given comparison and outcome, SR authors should draw in observational data [5]. This makes the most sense when

Prostatic arterial embolization for the treatment of lower urinary tract symptoms in men with benign prostatic hyperplasia

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To assess the effects of PAE for the treatment of LUTS in men with BPH.

Early stage cancer in older adults: Prostate-avoiding overtreatment and undertreatment

Abstract The diagnosis of prostate cancer in elderly men is likely to increase over the next several decades, owing to changing demographics and a rising population of men older than 65 years. Given the heterogeneity and well-documented challenges in screening, diagnosing, and managing indolent versus aggressive prostate cancer, the geriatric patient population is particularly vulnerable to prostate cancer treatment nuances. Clinicians must become familiar with geriatric assessment tools to better answer life-expectancy questions prior to counseling patients on treatment options. The preferences and values of patients and their families must always be considered when making screening and treatment decisions. Careful selection of patients following a holistic evaluation will not only minimize overtreatment and undertreatment of prostate cancer, but may also allow for the early identification of unique geriatric vulnerabilities and permit quicker interventions to improve the quality of life of these men during their elderly years.

Defining the publication source of high-quality evidence in urology: An analysis of EvidenceUpdates

To determine the publication sources of urology articles within EvidenceUpdates, a second‐order peer review system of the medical literature designed to identify high‐quality articles to support up‐to‐date and evidence‐based clinical decisions.

Racial disparities and considerations for active surveillance of prostate cancer

Active surveillance (AS) for the management of low-risk prostate cancer has been increasing and in the general population appears safe, allowing for a reduction in the harms of prostate cancer screening such as overtreatment. African-American (AA) men have overall worse outcomes from prostate cancer compared to Caucasian-American (CA) men for a variety of socioeconomic, cultural and possibly biologic reasons, thus complicating the use of AS in this population. Strategies for optimizing care and mitigating risk in this population include pursuing close surveillance with steadfast patient compliance, the use of multiparametric MRI with targeted biopsies including the anterior prostate to reduce the risk of undersampling, as well as a judicious and thoughtful incorporation of novel molecular biomarkers for risk stratification. Currently, there exists no direct data to suggest that AS cannot be safely carried out in AA men following an informed discussion and after engaging in shared decision making. Physicians should have a low threshold for consideration of definitive therapy. Additional efforts should be made in increasing the engagement of minority participants in clinical trials, to gain an improved representation of underserved populations in future research.