The Importance of Bone Health Management in Men with mCRPC - Editorial

It is well appreciated that men with bone metastases are at risk for fracture and symptomatic skeletal-related events (SREs), and that men on long-term potent hormonal therapies are at risk for fragility fractures due to ongoing bone loss. However, the utilization of denosumab and zoledronic acid, despite the widespread guideline recommendations for their consideration, remains low internationally. This was recently highlighted at ASCO 2021 with the PEACE3 clinical trial, where the mandated use of bone antiresorptive therapy in this bone mCRPC protocol of enzalutamide +/- radium-223 led to an improvement in the use of these agents in this population from 55% to 97%, and reduced the observed fracture rate at 18 months with enzalutamide alone from 22% to 2.6%, a major reduction in risk.1

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stephen j freedland

Stephen J. Freedland, MD

Stephen J. Freedland, MD, is director of the Center for Integrated Research in Cancer and Lifestyle and co-director of the Cancer Genetics and Prevention Program and Associate Director for Faculty Development at the Cedars-Sinai Samuel Oschin Comprehensive Cancer Institute. He is also a faculty physician in the Division of Urology within the Department of Surgery at Cedars-Sinai. He has served on numerous American Urological Association guideline panels for prostate cancer and co-chaired a prostate cancer guideline panel for the American Society of Clinical Oncology.

Dr. Freedland's clinical area of expertise focuses on urological diseases, particularly benign prostatic hyperplasia and prostate cancer. His approach toward cancer prevention and awareness focuses on treating the whole patient, not just the disease, by combining traditional Western medicine with complementary holistic interventions. His research interests include investigations on urological diseases and the role of diet, lifestyle and obesity in prostate cancer development and progression, as well as prostate cancer among racial groups and risk stratification for men with prostate cancer.


PCAN: July 2021

Bone Targeted Therapy and Skeletal Related Events in the Era of Enzalutamide and Abiraterone Acetate for Castration Resistant Prostate Cancer With Bone Metastases – Full Text Article

Background In an era of multiple life-prolonging therapies for metastatic castration-resistant prostate cancer (mCRPC), the optimal timing of initiation and duration of antiresorptive bone-targeted therapy (BTT) to prevent skeletal-related events (SREs) is unknown.

Methods To assess practice patterns of BTT use and its associations with clinical outcomes in a high-volume center in the modern era of metastatic CRPC management, a retrospective cohort of patients treated for mCRPC with BM between 2007 and 2017 was identified from a single institutions clinical research database.
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PCAN: July 2021

Novel Prostate Cancer Susceptibility Gene SP6 Predisposes Patients to Aggressive Disease - Full Text Article

Abstract

Prostate cancer (PrCa) is one of the most common cancers in men, but little is known about factors affecting its clinical outcomes. Genome-wide association studies have identified more than 170 germline susceptibility loci, but most of them are not associated with aggressive disease. We performed a genome-wide analysis of 185,478 SNPs in Finnish samples (2738 cases, 2400 controls) from the international Collaborative Oncological Gene-Environment Study (iCOGS) to find underlying PrCa risk variants. We identified a total of 21 common, low-penetrance susceptibility loci, including 10 novel variants independently associated with PrCa risk. Novel risk loci were located in the 8q24 (CASC8 rs16902147, OR 1.86, padj = 3.53 × 10−8 and rs58809953, OR 1.71, padj = 4.00 × 10−6 ; intergenic rs79012498, OR 1.81, padj = 4.26 × 10−8 ), 17q21 (SP6 rs2074187, OR 1.66, padj = 3.75 × 10−5 ), 11q13 (rs12795301, OR 1.42, padj = 2.89 × 10−5 ) and 8p21 (rs995432, OR 1.38, padj = 3.00 × 10−11) regions. Here, we describe SP6, a transcription factor gene, as a new, potentially high-risk gene for PrCa.
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PCAN: May 2021

Overall Survival of Black and White Men with Metastatic Castration-Resistant Prostate Cancer (mCRPC): A 20-Year Retrospective Analysis in the Largest Healthcare Trust in England - Full Text Article

Abstract

Background: Prostate cancer in black men is associated with poorer outcomes than their white counterparts. However, most studies reporting this disparity were conducted in localized prostate cancer and primarily in the United States.

Methods: Data regarding prostate cancer incidence and mortality for East London between 2008 and 2010 were obtained from the UK National Disease Registration Service. We further evaluated survival outcomes of 425 cases of mCRPC in St Bartholomew’s Hospital, East London, between 1997 and 2016, and analyzed whether ethnicity impacted on responses to different treatment types.

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PCAN: April 2021

Racial Disparity in the Utilization of Multiparametric MRI–Ultrasound Fusion Biopsy for the Detection of Prostate Cancer - Full Text Article

Background
Black men have significantly higher incidence and are up to three times more likely to die of prostate cancer (PCa) than White men. Multiparametric magnetic resonance imaging-ultrasound fusion biopsy (FBx) has emerged as a promising modality for the detection of PCa. The goal of our study is to identify differences in utilization of FBx between Black and White men presenting with suspicion of PCa.

Methods
We performed a retrospective review of Black and White men who presented with suspicion of PCa and required biopsy from January 2014 to December 2018. Multivariate logistic regression analysis was done to study the influence of race on the utilization of FBx.
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PCAN: March 2021

Androgen Receptor Gain in Circulating Free DNA and Splicing Variant 7 in Exosomes Predict Clinical Outcome in CRPC Patients Treated with Abiraterone and Enzalutamide - Full-Text Article

Background - Androgen receptor (AR) signaling inhibitors represent the standard treatment in metastatic castration resistance prostate cancer (mCRPC) patients. However, some patients display a primary resistance, and several studies investigated the role of the AR as a predictive biomarker of response to treatment. This study is aimed to evaluate the role of AR in liquid biopsy to predict clinical outcome to AR signaling inhibitors in mCRPC patients.

Methods - Six milliliters of plasma samples were collected before first-line treatment with abiraterone or enzalutamide. Circulating free DNA (cfDNA) and exosome-RNA were isolated for analysis of AR gain and AR splice variant 7 (AR-V7), respectively, by digital droplet PCR.
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PCAN: February 2021

Prospective Study to Define the Clinical Utility and Benefit of Decipher Testing in Men Following Prostatectomy - Full-Text Article

Background - Genomic classifiers (GC) have been shown to improve risk stratification post prostatectomy. However, their clinical benefit has not been prospectively demonstrated. We sought to determine the impact of GC testing on postoperative management in men with prostate cancer post prostatectomy.

Methods - Two prospective registries of prostate cancer patients treated between 2014 and 2019 were included. All men underwent Decipher tumor testing for adverse features post prostatectomy (Decipher Biosciences, San Diego, CA). The clinical utility cohort, which measured the change in treatment decision-making, captured pre- and postgenomic treatment recommendations from urologists across diverse practice settings (n = 3455). The clinical benefit cohort, which examined the difference in outcome, was from a single academic institution whose tumor board predefined “best practices” based on GC results (n = 135).
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