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Volume 19, Number 4Review Articles

The Use of Biomarkers in Prostate Cancer Screening and Treatment

Treatment Update

Joseph Renzulli IIAshley V AlfordJoseph M Brito IIIKamlesh K YadavShalini S YadavAshutosh K Tewari

Prostate cancer screening and diagnosis has been guided by prostate-specific antigen levels for the past 25 years, but with the most recent US Preventive Services Task Force screening recommendations, as well as concerns regarding overdiagnosis and overtreatment, a new wave of prostate cancer biomarkers has recently emerged. These assays allow the testing of urine, serum, or prostate tissue for molecular signs of prostate cancer, and provide information regarding both diagnosis and prognosis. In this review, we discuss 12 commercially available biomarker assays approved for the diagnosis and treatment of prostate cancer. The results of clinical validation studies and clinical decision-making studies are presented. This information is designed to assist urologists in making clinical decisions with respect to ordering and interpreting these tests for different patients. There are numerous fluid and biopsy-based genomic tests available for prostate cancer patients that provide the physician and patient with different information about risk of future disease and treatment outcomes. It is important that providers be able to recommend the appropriate test for each individual patient; this decision is based on tissue availability and prognostic information desired. Future studies will continue to emphasize the important role of genomic biomarkers in making individualized treatment decisions for prostate cancer patients. [Rev Urol. 2017;19(4):221–234 doi: 10.3909/riu0772] © 2018 MedReviews®, LLC

Prostate cancerBiomarkers4KscoreProlarisPCA3Prostate Health IndexApifinyMichigan Prostate ScoreSelectMDxConfirmMDxProMarkPTEN/TMPRSS2:ERGDecipher

Propensity scoreView Articles

Volume 20, Number 2Original Research

Balancing Confounding and Generalizability Using Observational, Real-world Data: 17-gene Genomic Prostate Score Assay Effect on Active Surveillance

Michael J KemeterPhillip G FebboSteven CanfieldJohn Hornberger

Randomized, controlled trials can provide high-quality, unbiased evidence for therapeutic interventions but are not always a practical or viable study design for certain healthcare decisions, such as those involving prognostic or predictive testing. Studies using large, real-world databases may be more appropriate and more generalizable to the intended target population of physicians and patients to answer these questions but carry potential for hidden bias. We illustrate several emerging methods of analyzing observational studies using propensity score matching (PSM) and coarsened exact matching (CEM). These advanced statistical methods are intended to reveal a “hidden experiment” within an observational database, and so refute or confirm a potential causal effect of assignment to an intervention and study outcome. We applied these methods to the Optum™ Research Database (ORD; Eden Prairie, MN) of electronic health records and administrative claims data to assess the effect of the 17-gene Genomic Prostate Score® (GPS™; Genomic Health, Redwood City, CA) assay on use of active surveillance (AS). In a traditional multivariable logistic regression, the GPS assay increased the use of AS by 29% (95% CI, 24%-33%). Upon applying the matching methods, the effect of the GPS assay on AS use varied between 27% and 80% and the matched data were significant among all algorithms. All matching algorithms performed well in identifying matched data that improved the imbalance in baseline covariates. By using different matching methods to assess causal inference in an observational database, we provide further confidence that the effect of the GPS assay on AS use is statistically significant and unlikely to be a result of confounding due to differences in baseline characteristics of the patients or the settings in which they were seen. [Rev Urol. 2018;20(2):69–76 doi: 10.3909/riu0799] © 2018 MedReviews, LLC®

Prostate cancerActive surveillanceEvidence-based practiceComparative effectiveness researchGenomic biomarkerPropensity scoreMatching

Prostaglandin EView Articles

Volume 17, Number 2Review Articles

Penile Rehabilitation Strategies Among Prostate Cancer Survivors

Treatment Update

Fouad AounAlexandre PeltierRoland van Velthoven

Despite advances in technical and surgical approaches, erectile dysfunction (ED) remains the most common complication among prostate cancer survivors, adversely impacting quality of life. This article analyzes the concept and rationale of ED rehabilitation programs in prostate cancer patients. Emphasis is placed on the pathophysiology of ED after diagnosis and treatment of prostate cancer to understand the efficacy of rehabilitation programs in clinical practice. Available evidence shows that ED is a transient complication following prostate biopsy and cancer diagnosis, with no evidence to support rehabilitation programs in these patients. A small increase in ED and in the use of phosphodiesterase type 5 (PDE5) inhibitors was reported in patients under active surveillance. Patients should be advised that active surveillance is unlikely to severely affect erectile function, but clinically significant changes in sexual function are possible. Focal therapy could be an intermediate option for patients demanding treatment/refusing active surveillance and invested in maintaining sexual activity. Unlike radical prostatectomy, there is no support for PDE5 inhibitor use to prevent ED after highly conformal external radiotherapy or low-dose rate brachytherapy. Despite progress in the understanding of the pathophysiologic mechanisms responsible for ED in prostate cancer patients, the success rates of rehabilitation programs remain low in clinical practice. Alternative strategies to prevent ED appear warranted, with attention toward neuromodulation, nerve grafting, nerve preservation, stem cell therapy, investigation of neuroprotective interventions, and further refinements of radiotherapy dosing and delivery methods. [Rev Urol. 2015;17(2):58-68 doi: 10.3909/riu0652] © 2015 MedReviews®, LLC

Prostate cancerErectile dysfunctionPenile rehabilitationPhosphodiesterase type 5 inhibitorProstaglandin E

Prostate cancer antigen 3View Articles
Prostate cancer prognosisView Articles

Volume 17, Number 4Original Research

The 4Kscore® Test Reduces Prostate Biopsy Rates in Community and Academic Urology Practices

Jason HafronStephen M ZappalaDipen J ParekhDanielle OsterhoutJeffrey SchockRandy M ChudlerGregory M OldfordKenneth M KernenBadrinath R Konety

There is significant concern regarding prostate cancer screening because of the potential for overdiagnosis and overtreatment of men who are discovered to have abnormal prostate specific antigen (PSA) levels and/or digital rectal examination (DRE) results. The 4Kscore® Test (OPKO Diagnostics, LLC) is a blood test that utilizes four kallikrein levels plus clinical information in an algorithm to calculate an individual’s percentage risk (< 1% to > 95%) for aggressive prostate cancer (Gleason score ≥ 7) on prostate biopsy. The 4Kscore Test, as a follow-up test after abnormal PSA and/or DRE test results, has been shown to improve the specificity for predicting the risk of aggressive prostate cancer and reduce unnecessary prostate biopsies. A clinical utility study was conducted to assess the influence of the 4Kscore Test on the decision to perform prostate biopsies in men referred to urologists for abnormal PSA and/or DRE results. The study population included 611 patients seen by 35 academic and community urologists in the United States. Urologists ordered the 4Kscore Test as part of their assessment of men referred for abnormal PSA and/or DRE test results. Results for the patients were stratified into low risk (< 7.5%), intermediate risk (7.5%-19.9%), and high risk (≥ 20%) for aggressive prostate cancer. The 4Kscore Test results influenced biopsy decisions in 88.7% of the men. Performing the 4Kscore Test resulted in a 64.6% reduction in prostate biopsies in patients; the actual percentage of cases not proceeding to biopsy were 94.0%, 52.9%, and 19.0% for men who had low-, intermediate-, and high-risk 4Kscore Test results, respectively. A higher 4Kscore Test was associated with greater likelihood of having a prostate biopsy (P < 0.001). Among the 171 patients who had a biopsy, the 4Kscore risk category is strongly associated with biopsy pathology. The 4Kscore Test, as a follow-up test for an abnormal PSA and/or DRE results, significantly influenced the physician and patient shared decision in clinical practice, which led to a reduction in prostate biopsies while increasing the probability of detecting aggressive cancer. [Rev Urol. 2015;17(4):231-240 doi: 10.3909/riu0699] © 2016 MedReviews®, LLC

Prostate cancerProstate-specific antigen4KscoreGleason scoreDigital rectal examinationBiopsy rateProstate cancer prognosis

Prostate cancer, localizedView Articles

Volume 10, Number 4Review Articles

Vascular Targeted Photodynamic Therapy for Localized Prostate Cancer

Treatment Update

Herbert Lepor

Survival for men diagnosed with prostate cancer directly depends on the stage and grade of the disease at diagnosis. Prostate cancer screening has greatly increased the ability to diagnose small and low-grade cancers that are amenable to cure. However, widespread prostate-specific antigen screening exposes many men with low-risk cancers to unnecessary complications associated with treatment for localized disease without any survival advantage. One challenge for urological surgeons is to develop effective treatment options for low-risk disease that are associated with fewer complications. Minimally invasive ablative treatments for localized prostate cancer are under development and may represent a preferred option for men with low-risk disease who want to balance the risks and benefits of treatment. Vascular targeted photodynamic therapy (VTP) is a novel technique that is being developed for treating prostate cancer. Recent advances in photodynamic therapy have led to the development of photosynthesizers that are retained by the vascular system, which provides the opportunity to selectively ablate the prostate with minimal collateral damage to other structures. The rapid clearance of these new agents negates the need to avoid exposure to sunlight for long periods. Presented herein are the rationale and preliminary data for VTP for localized prostate cancer. [Rev Urol. 2008;10(4):254-261]

Vascular targeted photodynamic therapyPhotodynamic therapyProstate cancer, localizedMinimally invasive ablative treatment for prostate cancerWST-09WST-11PadoporfinPalladium bacteriopheophorbide

Prostate carcinomaView Articles