Validation of the Decipher Test for Predicting Distant Metastatic Recurrence in Men with High-risk Nonmetastatic Prostate Cancer 10 Years After Surgery.

Background: Decipher is a genomic classifier designed to predict the development of distant metastases after surgical treatment of prostate cancer (PC). Its long-term prognostic role in a high-risk PC population has not been investigated previously.

Objective: To determine the prognostic role of the Decipher genomic classifier in two high-risk PC case-control studies.

Correlation between MRI phenotypes and a genomic classifier of prostate cancer: preliminary findings.

Objectives: We sought to evaluate the correlation between MRI phenotypes of prostate cancer as defined by PI-RADS v2 and the Decipher Genomic Classifier (used to estimate the risk of early metastases).

Methods: This single-center, retrospective study included 72 nonconsecutive men with prostate cancer who underwent MRI before radical prostatectomy performed between April 2014 and August 2017 and whose MRI registered lesions were microdissected from radical prostatectomy specimens and then profiled using Decipher (89 lesions; 23 MRI invisible [PI-RADS v2 scores ≤ 2] and 66 MRI visible [PI-RADS v2 scores ≥ 3]). Linear regression analysis was used to assess clinicopathologic and MRI predictors of Decipher results; correlation coefficients (r) were used to quantify these associations.

The Diverse Genomic Landscape of Clinically Low-risk Prostate Cancer.

Background: Among men with clinically low-risk prostate cancer, we have previously documented heterogeneity in terms of clinical characteristics and genomic risk scores.

Objective: To further study the underlying tumor biology of this patient population, by interrogating broader patterns of gene expression among men with clinically low-risk tumors.

Design, Setting, And Participants: Prostate biopsies from 427 patients considered potentially suitable for active surveillance underwent central pathology review and genome-wide expression profiling.

Neoadjuvant degarelix with or without apalutamide followed by radical prostatectomy for intermediate and high-risk prostate cancer: ARNEO, a randomized, double blind, placebo-controlled trial.

Background: Recent retrospective data suggest that neoadjuvant androgen deprivation therapy can improve the prognosis of high-risk prostate cancer (PCa) patients. Novel androgen receptor pathway inhibitors are nowadays available for treatment of metastatic PCa and these compounds are promising for early stage disease. Apalutamide is a pure androgen antagonist with a very high affinity with the androgen receptor.

Prevention of Low Cardiac Output Syndrome After Pediatric Cardiac Surgery: A Double-Blind Randomized Clinical Pilot Study Comparing Dobutamine and Milrinone.

Objectives: Dobutamine and milrinone are commonly used after open-heart surgery to prevent or treat low cardiac output syndrome. We sought to compare efficacy and safety of these drugs in pediatric patients.

Design: Prospective, single-center, double-blinded, randomized clinical pilot study.

Development and Validation of a Novel Integrated Clinical-Genomic Risk Group Classification for Localized Prostate Cancer.

Purpose It is clinically challenging to integrate genomic-classifier results that report a numeric risk of recurrence into treatment recommendations for localized prostate cancer, which are founded in the framework of risk groups. We aimed to develop a novel clinical-genomic risk grouping system that can readily be incorporated into treatment guidelines for localized prostate cancer. Materials and Methods Two multicenter cohorts (n = 991) were used for training and validation of the clinical-genomic risk groups, and two additional cohorts (n = 5,937) were used for reclassification analyses.

Gene Expression Correlates of Site-specific Metastasis Among Men With Lymph Node Positive Prostate Cancer Treated With Radical Prostatectomy: A Case Series.

Predictors of site-specific metastasis after radical prostatectomy (RP) are unknown despite prognostic differences between metastatic sites. We performed RNA expression analysis for 19 genes known to be correlated with aggressive prostate cancer in primary tumors of 63 men pN+ at RP (N = 35 developing metastases after RP vs N = 28 without metastases after RP). Of the men developing metastases, 22 (62.

Transcriptome Wide Analysis of Magnetic Resonance Imaging-targeted Biopsy and Matching Surgical Specimens from High-risk Prostate Cancer Patients Treated with Radical Prostatectomy: The Target Must Be Hit.

Background: The most suspicious lesions on multiparametric magnetic resonance imaging (MRI) may be representative of final pathology.

Objective: We connect imaging with high-precision spatial annotation of biopsies and genomic cancer signatures to compare the genomic signals of the index lesion and biopsy cores of adjacent and far away locations.

Design, Setting, And Participants: Eleven patients diagnosed with high-risk prostate cancer on MRI/transrectal ultrasound-fusion biopsy (Bx) and treated with radical prostatectomy (RP).

Ability of a Genomic Classifier to Predict Metastasis and Prostate Cancer-specific Mortality after Radiation or Surgery based on Needle Biopsy Specimens.

Background: Decipher is a validated genomic classifier developed to determine the biological potential for metastasis after radical prostatectomy (RP).

Objective: To evaluate the ability of biopsy Decipher to predict metastasis and Prostate cancer-specific mortality (PCSM) in primarily intermediate- to high-risk patients treated with RP or radiation therapy (RT).

Design, Setting, And Participants: Two hundred and thirty-five patients treated with either RP (n=105) or RT±androgen deprivation therapy (n=130) with available genomic expression profiles generated from diagnostic biopsy specimens from seven tertiary referral centers.

Impact of Molecular Subtypes in Muscle-invasive Bladder Cancer on Predicting Response and Survival after Neoadjuvant Chemotherapy.

Background: An early report on the molecular subtyping of muscle-invasive bladder cancer (MIBC) by gene expression suggested that response to neoadjuvant chemotherapy (NAC) varies by subtype.

Objective: To investigate the ability of molecular subtypes to predict pathological downstaging and survival after NAC.

Design, Setting, And Participants: Whole transcriptome profiling was performed on pre-NAC transurethral resection specimens from 343 patients with MIBC.

Individual Patient-Level Meta-Analysis of the Performance of the Decipher Genomic Classifier in High-Risk Men After Prostatectomy to Predict Development of Metastatic Disease.

Purpose To perform the first meta-analysis of the performance of the genomic classifier test, Decipher, in men with prostate cancer postprostatectomy. Methods MEDLINE, EMBASE, and the Decipher genomic resource information database were searched for published reports between 2011 and 2016 of men treated by prostatectomy that assessed the benefit of the Decipher test. Multivariable Cox proportional hazards models fit to individual patient data were performed; meta-analyses were conducted by pooling the study-specific hazard ratios (HRs) using random-effects modeling.

Her2 alterations in muscle-invasive bladder cancer: Patient selection beyond protein expression for targeted therapy.

Although the introduction of novel targeted agents has improved patient outcomes in several human cancers, no such advance has been achieved in muscle-invasive bladder cancer (MIBC). However, recent sequencing efforts have begun to dissect the complex genomic landscape of MIBC, revealing distinct molecular subtypes and offering hope for implementation of targeted therapies. Her2 (ERBB2) is one of the most established therapeutic targets in breast and gastric cancer but agents targeting Her2 have not yet demonstrated anti-tumor activity in MIBC.

Cost-effectiveness of the Decipher Genomic Classifier to Guide Individualized Decisions for Early Radiation Therapy After Prostatectomy for Prostate Cancer.

Background: Controversy exists regarding the effectiveness of early adjuvant versus salvage radiation therapy after prostatectomy for prostate cancer. Estimates of prostate cancer progression from the Decipher genomic classifier (GC) could guide informed decision-making and improve the outcomes for patients.

Materials And Methods: We developed a Markov model to compare the costs and quality-adjusted life years (QALYs) associated with GC-based treatment decisions regarding adjuvant therapy after prostatectomy with those of 2 control strategies: usual care (determined from patterns of care studies) and the alternative of 100% adjuvant radiation therapy.

Decipher correlation patterns post prostatectomy: initial experience from 2 342 prospective patients.

Background: Currently, there are multiple commercially available RNA-based biomarkers that are Medicare approved and suggested for use by the National Comprehensive Cancer Network guidelines. There is uncertainty as to which patients benefit from genomic testing and for whom these tests should be ordered. Here, we examined the correlation patterns of Decipher assay to understand the relationship between the Decipher and patient tumor characteristics.

Association of multiparametric MRI quantitative imaging features with prostate cancer gene expression in MRI-targeted prostate biopsies.

Standard clinicopathological variables are inadequate for optimal management of prostate cancer patients. While genomic classifiers have improved patient risk classification, the multifocality and heterogeneity of prostate cancer can confound pre-treatment assessment. The objective was to investigate the association of multiparametric (mp)MRI quantitative features with prostate cancer risk gene expression profiles in mpMRI-guided biopsies tissues.

Prediction of Lymph Node Metastasis in Patients with Bladder Cancer Using Whole Transcriptome Gene Expression Signatures.

Purpose: Clinical staging in patients with muscle invasive bladder cancer misses up to 25% of lymph node metastasis. These patients are at high risk for disease recurrence and improved clinical staging is critical to guide management.

Materials And Methods: Whole transcriptome expression profiles were generated in 199 patients who underwent radical cystectomy and extended pelvic lymph node dissection.

Decipher Genomic Classifier Measured on Prostate Biopsy Predicts Metastasis Risk.

Objectives: To evaluate the ability of the Decipher genomic classifier in predicting metastasis from analysis of prostate needle biopsy diagnostic tumor tissue specimens.

Materials And Methods: Fifty-seven patients with available biopsy specimens were identified from a cohort of 169 men treated with radical prostatectomy in a previously reported Decipher validation study at Cleveland Clinic. A Cox multivariable proportional hazards model and survival C-index were used to evaluate the performance of Decipher.

Utilization of a Genomic Classifier for Prediction of Metastasis Following Salvage Radiation Therapy after Radical Prostatectomy.

Background: Despite salvage radiation therapy (SRT) for recurrent prostate cancer (PCa) after radical prostatectomy (RP), some patients still progress to metastases. Identifying these men would allow them to undergo systemic therapy including testing novel therapies to reduce metastases risk.

Objective: To test whether the genomic classifier (GC) predicts development of metastatic disease.

Validation of a Genomic Classifier for Predicting Post-Prostatectomy Recurrence in a Community Based Health Care Setting.

Purpose: We determined the value of Decipher®, a genomic classifier, to predict prostate cancer outcomes among patients after prostatectomy in a community health care setting.

Materials And Methods: We examined the experience of 224 men treated with radical prostatectomy from 1997 to 2009 at Kaiser Permanente Northwest, a large prepaid health plan in Portland, Oregon. Study subjects had aggressive prostate cancer with at least 1 of several criteria such as preoperative prostate specific antigen 20 ng/ml or greater, pathological Gleason score 8 or greater, stage pT3 disease or positive surgical margins at prostatectomy.

Tissue-based Genomics Augments Post-prostatectomy Risk Stratification in a Natural History Cohort of Intermediate- and High-Risk Men.

Background: Radical prostatectomy (RP) is a primary treatment option for men with intermediate- and high-risk prostate cancer. Although many are effectively cured with local therapy alone, these men are by definition at higher risk of adverse pathologic features and clinical disease recurrence. It has been shown that the Decipher test predicts metastatic progression in cohorts that received adjuvant and salvage therapy following RP.

Evaluating the clinical impact of a genomic classifier in prostate cancer using individualized decision analysis.

Background: Currently there is controversy surrounding the optimal way to treat patients with prostate cancer in the post-prostatectomy setting. Adjuvant therapies carry possible benefits of improved curative results, but there is uncertainty in which patients should receive adjuvant therapy. There are concerns about giving toxicity to a whole population for the benefit of only a subset.

Clinical and genomic analysis of metastatic prostate cancer progression with a background of postoperative biochemical recurrence.

Objective: To better characterize the genomics of patients with biochemical recurrence (BCR) who have metastatic disease progression in order to improve treatment decisions for prostate cancer.

Methods: The expression profiles of three clinical outcome groups after radical prostatectomy (RP) were compared: those with no evidence of disease (NED; n = 108); those with BCR (rise in prostate-specific antigen [PSA] level without metastasis; n = 163); and those with metastasis (n = 192). The patients were profiled using Human Exon 1.

A genomic classifier improves prediction of metastatic disease within 5 years after surgery in node-negative high-risk prostate cancer patients managed by radical prostatectomy without adjuvant therapy.

Background: Surgery is a standard first-line therapy for men with intermediate- or high-risk prostate cancer. Clinical factors such as tumor grade, stage, and prostate-specific antigen (PSA) are currently used to identify those who are at risk of recurrence and who may benefit from adjuvant therapy, but novel biomarkers that improve risk stratification and that distinguish local from systemic recurrence are needed.

Objective: To determine whether adding the Decipher genomic classifier, a validated metastasis risk-prediction model, to standard risk-stratification tools (CAPRA-S and Stephenson nomogram) improves accuracy in predicting metastatic disease within 5 yr after surgery (rapid metastasis [RM]) in an independent cohort of men with adverse pathologic features after radical prostatectomy (RP).

Discovery and validation of novel expression signature for postcystectomy recurrence in high-risk bladder cancer.

Background: Nearly half of muscle-invasive bladder cancer patients succumb to their disease following cystectomy. Selecting candidates for adjuvant therapy is currently based on clinical parameters with limited predictive power. This study aimed to develop and validate genomic-based signatures that can better identify patients at risk for recurrence than clinical models alone.

Effect of a genomic classifier test on clinical practice decisions for patients with high-risk prostate cancer after surgery.

Objectives: To evaluate the impact of a genomic classifier (GC) test for predicting metastasis risk after radical prostatectomy (RP) on urologists' decision-making about adjuvant treatment of patients with high-risk prostate cancer.

Subjects And Methods: Patient case history was extracted from the medical records of each of the 145 patients with pT3 disease or positive surgical margins (PSMs) after RP treated by six high-volume urologists, from five community practices. GC results were available for 122 (84%) of these patients.