Impact of Gene Expression Classifier Testing on Adjuvant Treatment Following Radical Prostatectomy: The G-MINOR Prospective Randomized Cluster-crossover Trial.

Background And Objective: Decipher is a tissue-based genomic classifier (GC) developed and validated in the post-radical prostatectomy (RP) setting as a predictor of metastasis. We conducted a prospective randomized controlled cluster-crossover trial assessing the use of Decipher to determine its impact on adjuvant treatment after RP.

Methods: Eligible patients had undergone RP within 9 mo of enrollment, had pT3-4 disease and/or positive surgical margins, and prostate-specific antigen <0.

Development and Optimization of a Subtraction-Normalized Immunocyte Profiling Signature for Prostate Cancer Active Surveillance Risk Stratification.

Purpose: Less invasive decision support tools are desperately needed to identify occult high-risk disease in men with prostate cancer (PCa) on active surveillance (AS). For a variety of reasons, many men on AS with low- or intermediate-risk disease forgo the necessary repeat surveillance biopsies needed to identify potentially higher-risk PCa. Here, we describe the development of a blood-based immunocyte transcriptomic signature to identify men harboring occult aggressive PCa.

Positive Impact of Implementing a Comprehensive Genetic Testing Protocol for Prostate Cancer Patients in a Multi-disciplinary Uro-oncology Practice.

Introduction: Prior to the 2017 Philadelphia Consensus Conference guidelines, genetic testing for prostate cancer was conducted based on personal and family history of malignancy pursuant to National Comprehensive Cancer Network recommendations. The updated 2019 guidelines addressed the subject of genetic testing by endorsing point-of-care genetic testing and referral to genetic counseling. However, limited literature is available regarding successful implementation of a streamlined method for genetic testing.

The Diagnosis of Urinary Tract Infections Using a Novel At-home Testing Protocol to Enhance Telemedicine: A Retrospective Analysis.

Objective: To retrospectively analyze a novel courier-based home urine collection strategy for patients with symptoms of urinary tract infections (UTIs). This model was developed to provide patient care using telehealth during the coronavirus 2019 pandemic.

Methods: We analyzed data from 2206 patients with symptomatic UTIs to investigate the efficacy of a home urine collection protocol.

Evaluation of an RNAseq-Based Immunogenomic Liquid Biopsy Approach in Early-Stage Prostate Cancer.

The primary objective of this study is to detect biomarkers and develop models that enable the identification of clinically significant prostate cancer and to understand the biologic implications of the genes involved. Peripheral blood samples (1018 patients) were split chronologically into independent training ( = 713) and validation ( = 305) sets. Whole transcriptome RNA sequencing was performed on isolated phagocytic CD14+ and non-phagocytic CD2+ cells and their gene expression levels were used to develop predictive models that correlate to adverse pathologic features.

Bacterial Interactions as Detected by Pooled Antibiotic Susceptibility Testing (P-AST) in Polymicrobial Urine Specimens.

Introduction: Antimicrobial susceptibility is well characterized in monomicrobial infections, but bacterial species often coexist with other bacterial species. Antimicrobial susceptibility is often tested against single bacterial isolates; this approach ignores interactions between cohabiting bacteria that could impact susceptibility. Here, we use Pooled Antibiotic Susceptibility Testing to compare antimicrobial susceptibility patterns exhibited by polymicrobial and monomicrobial urine specimens obtained from patients with urinary tract infection symptoms.

Multiplex PCR Based Urinary Tract Infection (UTI) Analysis Compared to Traditional Urine Culture in Identifying Significant Pathogens in Symptomatic Patients.

Objective: To evaluate whether multiplex PCR-based molecular testing is noninferior to urine culture for detection of bacterial infections in symptomatic patients.

Methods: Retrospective record review of 582 consecutive elderly patients presenting with symptoms of lower urinary tract infection (UTI) was conducted. All patients had traditional urine cultures and PCR molecular testing run in parallel.

Clinical outcomes in men with prostate cancer who selected active surveillance using a clinical cell cycle risk score.

To evaluate active surveillance (AS) selection, safety and durability among men with low-risk prostate cancer assessed using the clinical cell cycle risk (CCR) score, a combined clinical and molecular score. Initial treatment selection (AS vs treatment) and duration of AS were evaluated for men with low-risk prostate cancer according to the CCR score and National Comprehensive Cancer Network guidelines. Adverse events included biochemical recurrence and metastasis.

Urinary Molecular Biomarker Test Impacts Prostate Biopsy Decision Making in Clinical Practice.

Introduction: There is an unmet need for noninvasive methods to better identify patients at increased risk for clinically significant prostate cancer. SelectMDx® is a molecular urine test validated for the detection of Gleason score 7 and higher cancers (ISUP [International Society of Urological Pathology] Grade Group 2-5). In this multicenter trial we evaluated the test's impact on prostate biopsy decision making in clinical practice.

Specimen Provenance Testing Identifies Contamination That Affects Molecular Prognostic Assay Results in Prostate Cancer Biopsy Specimens.

Objective: To determine if tissue contamination in histologic specimens can significantly affect the results of prognostic molecular markers that are routinely used as confirmatory tests to safely assign appropriate candidates to prostate cancer active surveillance protocols.

Materials And Methods: This study evaluates 2134 cases from a single, large urology practice that were successfully tested for DNA specimen provenance verification using short tandem repeat analysis for the presence of a significant level of contaminating DNA. After removal of the contamination, 5 of the samples were retested, and the results of the molecular diagnostic test were compared.

Prostatectomy-based validation of combined urine and plasma test for predicting high grade prostate cancer.

Background: Distinguishing between low- and high-grade prostate cancers (PCa) is important, but biopsy may underestimate the actual grade of cancer. We have previously shown that urine/plasma-based prostate-specific biomarkers can predict high grade PCa. Our objective was to determine the accuracy of a test using cell-free RNA levels of biomarkers in predicting prostatectomy results.

Clinical Utility of Gene Expression Classifiers in Men With Newly Diagnosed Prostate Cancer.

Purpose: Tissue-based gene expression classifiers (GECs) may assist with management decisions in patients with newly diagnosed prostate cancer. We sought to assess the current use of GEC tests and determine how the test results are associated with primary disease management.

Methods: In this observational study, patients diagnosed with localized prostate cancer were tracked through the Michigan Urological Surgery Improvement Collaborative registry.

A Multi-Center Prospective Study to Validate an Algorithm Using Urine and Plasma Biomarkers for Predicting Gleason ≥3+4 Prostate Cancer on Biopsy.

Unnecessary biopsies and overdiagnosis of prostate cancer (PCa) remain a serious healthcare problem. We have previously shown that urine- and plasma-based prostate-specific biomarkers when combined can predict high grade prostate cancer (PCa). To further validate this test, we performed a prospective multicenter study recruiting patients from community-based practices.

The clinical and economic implications of specimen provenance complications in diagnostic prostate biopsies.

Purpose: Inaccurate diagnoses of prostate cancer can result from transposition or contamination of patient biopsy specimens, which are known as specimen provenance complications. We assessed the clinical and economic burden of specimen provenance complications in prostate biopsies in the United States.

Materials And Methods: We performed a comprehensive, systematic review of the literature to approximate the effect of specimen provenance complications on direct medical costs, patient QALYs and medicolegal costs.

Reduced Rate of Repeated Prostate Biopsies Observed in ConfirmMDx Clinical Utility Field Study.

Background: The diagnosis of prostate cancer is dependent on histologic confirmation in biopsy core tissues. The biopsy procedure is invasive, puts the patient at risk for complications, and is subject to significant sampling errors. An epigenetic test that uses methylation-specific polymerase chain reaction to determine the epigenetic status of the prostate cancer-associated genes GSTP1, APC, and RASSF1 has been clinically validated and is used in clinical practice to increase the negative predictive value in men with no history of prostate cancer compared with standard histopathology.

The E2F1/DNMT1 axis is associated with the development of AR negative castration resistant prostate cancer.

Background: Research on castration resistant prostate cancer (CRPC) has focused primarily on functional alterations of the androgen receptor (AR). However, little is known about the loss of AR gene expression itself and the possible contribution of AR negative cells to CRPC.

Methods: Human and murine prostate cancer tissue microarrays (TMAs) were evaluated with antibodies specific for E2F1, DNA methyltransferase 1 or AR.

Repression of androgen receptor transcription through the E2F1/DNMT1 axis.

Although androgen receptor (AR) function has been extensively studied, regulation of the AR gene itself has been much less characterized. In this study, we observed a dramatic reduction in the expression of androgen receptor mRNA and protein in hyperproliferative prostate epithelium of keratin 5 promoter driven E2F1 transgenic mice. To confirm an inhibitory function for E2F1 on AR transcription, we showed that E2F1 inhibited the transcription of endogenous AR mRNA, subsequent AR protein, and AR promoter activity in both human and mouse epithelial cells.

Molecular markers that can be utilized in diet and dietary supplement research.

Prostate and other cancers have a multitude of potential markers that can be used in laboratory and clinical studies of diet and dietary supplement interventions. More overt clinical markers include imaging tests, biopsy samples, prostate-specific antigen kinetics, and urinary testing. Many molecular markers are currently available, including antiapoptotic and apoptotic proteins, cell adhesion molecules, cell cycle compounds, growth factors, angiogenic markers, and proliferative and inflammatory signals.

Histotripsy of the prostate: dose effects in a chronic canine model.

Objectives: To develop the technique of histotripsy ultrasound therapy as a noninvasive treatment for benign prostatic hyperplasia and to examine the histotripsy dose-tissue response effect over time to provide an insight for treatment optimization. We have previously demonstrated the feasibility of prostate histotripsy fractionation in a canine model.

Methods: Various doses of histotripsy were applied transabdominally to the prostates of 20 canine subjects.

Rational approach to implementation of prostate cancer antigen 3 into clinical care.

Background: Prostate cancer antigen 3 (PCA3) encodes a prostate-specific messenger ribonucleic acid (mRNA) that serves as the target for a novel urinary molecular assay for prostate cancer detection. The objective of the current study was to evaluate the ability of PCA3, added to measurements of serum prostate-specific antigen (PSA), to predict cancer detection by extended template biopsy.

Methods: Between September 2006 and December 2007, whole urine samples were collected after attentive digital rectal examinations from 187 men before they underwent ultrasound-guided, 12-core prostate biopsy in a urology outpatient clinic.

Is residual neurovascular tissue on prostatectomy specimens associated with surgeon intent at nerve-sparing and postoperative quality of life measures?

Objectives: Preservation of periprostatic neurovascular tissue at the time of radical prostatectomy has been correlated with subsequent erectile function and urinary continence. We evaluated whether the amount of neurovascular tissue identified on prostatectomy specimens correlated with surgeon's intention of nerve-sparing and/or predicted quality of life outcomes.

Materials And Methods: Radical prostatectomy specimens from 60 patients were evaluated by 2 pathologists for residual neurovascular bundle tissue.

Body composition and serum prostate-specific antigen: review and findings from Flint Men's Health Study.

Recent studies have suggested that obesity is associated with lower serum prostate-specific antigen levels, perhaps influencing the recommendation for prostate biopsy and potentially explaining part of the observed poorer prognosis among obese men. African-American men have the greatest rates of prostate cancer and are more likely to die of the disease, making early detection a priority in this group. We present findings from the Flint Men's Health Study, a study of African-American men, that are consistent with most studies suggesting that overweight men have prostate-specific antigen levels that are 0.

X-linked inhibitor of apoptosis deficiency in the TRAMP mouse prostate cancer model.

Deregulation of apoptotic pathways plays a central role in cancer pathogenesis. X-linked inhibitor of apoptosis protein (XIAP), is an antiapoptotic molecule, whose elevated expression has been observed in tumor specimens from patients with prostate carcinoma. Studies in human cancer cell culture models and xenograft tumor models have demonstrated that loss of XIAP sensitizes cancer cells to apoptotic stimuli and abrogates tumor growth.

BK virus as a cofactor in the etiology of prostate cancer in its early stages.

Prostate cancer has been projected to cause almost 10% of all male cancer deaths in the United States in 2007. The incidence of mutations in the tumor suppressor genes Rb1 and p53, especially in the early stages of the disease, is low compared to those for other cancers. This has led to the hypothesis that a human virus such as BK virus (BKV), which establishes a persistent subclinical infection in the urinary tract and encodes oncoproteins that interfere with these tumor suppressor pathways, is involved.