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Metastatic prostatic cancer clinical treatment

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https://www.readbyqxmd.com/read/29222530/seizure-rates-in-enzalutamide-treated-men-with-metastatic-castration-resistant-prostate-cancer-and-risk-of-seizure-the-upward-study
#1
Susan Slovin, William Clark, Joan Carles, Andrew Krivoshik, Jung Wook Park, Fong Wang, Daniel George
Importance: The androgen receptor inhibitor enzalutamide prolongs survival in men with metastatic castration-resistant prostate cancer (mCRPC). In controlled clinical studies, 0.5% (10 of 2051) of patients experienced seizure, but patients with a history of or risk factors for seizure were excluded. Men with mCRPC and seizure risk factors have an estimated seizure rate of 2.8 per 100 patient-years without enzalutamide exposure. Objective: To assess seizure incidence in patients with seizure risk factors who were receiving enzalutamide for mCRPC...
December 7, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/29211405/high-intensity-focused-ultrasound-hifu-as-salvage-therapy-for-radio-recurrent-prostate-cancer-predictors-of-disease-response
#2
Shawn Dason, Nathan C Wong, Christopher B Allard, Jen Hoogenes, William Orovan, Bobby Shayegan
BACKGROUND: Some men with localized radio-recurrent prostate cancer may benefit from salvage high-intensity focused ultrasound (HIFU). Herein, we describe oncologic outcomes and predictors of disease response after salvage whole gland HIFU from our prospective cohort. MATERIALS AND METHODS: Patients with localized radio-recurrent prostate cancer were prospectively enrolled from January 2005 to December 2014. Participants had to meet both biochemical and histological definitions of recurrence...
December 7, 2017: International Braz J Urol: Official Journal of the Brazilian Society of Urology
https://www.readbyqxmd.com/read/29202848/downregulation-of-mir-141-3p-promotes-bone-metastasis-via-activating-nf-%C3%AE%C2%BAb-signaling-in-prostate-cancer
#3
Shuai Huang, Qingde Wa, Jincheng Pan, Xinsheng Peng, Dong Ren, Yan Huang, Xiao Chen, Yubo Tang
BACKGROUND: Clinically, prostate cancer (PCa) exhibits a high avidity to metastasize to bone. miR-141-3p is an extensively studied miRNA in cancers and downregulation of miR-141-3p has been widely reported to be involved in the progression and metastasis of several human cancer types. However, the clinical significance and biological roles of miR-141-3p in bone metastasis of PCa are still unclear. METHODS: miR-141-3p expression was examined in 89 non-bone metastatic and 52 bone metastatic PCa tissues by real-time PCR...
December 4, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/29198331/biomarkers-in-prostate-cancer-current-clinical-utility-and-future-perspectives
#4
REVIEW
Alexander Kretschmer, Derya Tilki
Current tendencies in the treatment course of prostate cancer patients increase the need for reliable biomarkers that help in decision-making in a challenging clinical setting. Within the last decade, several novel biomarkers have been introduced. In the following comprehensive review article, we focus on diagnostic (PHI®, 4K score, SelectMDx®, ConfirmMDx®, PCA3, MiPS, ExoDX®, mpMRI) and prognostic (OncotypeDX GPS®, Prolaris®, ProMark®, DNA-ploidy, Decipher®) biomarkers that are in widespread clinical use and are supported by evidence...
December 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/29196208/eradicate-a-prospective-evaluation-combining-radium-223-dichloride-and-abiraterone-acetate-plus-prednisone-in-patients-with-castration-resistant-prostate-cancer
#5
Neal D Shore, Ronald F Tutrone, Neil F Mariados, Luke T Nordquist, Bryan A Mehlhaff, Karyn J Steere, Stacey S Harrelson
BACKGROUND: Multiple castration-resistant prostate cancer (CRPC) therapies are approved by the United States Food and Drug Administration. Radium-223 dichloride (Ra-223) with abiraterone acetate plus prednisone have different mechanisms of action and distinct off-target side-effect profiles. We prospectively investigated their combined safety, tolerability, and patient-reported outcome measures. PATIENTS AND METHODS: eRADicAte, an investigator-initiated, phase II trial, studied 31 patients with metastatic CRPC, from 5 United States uro-oncology research sites...
November 7, 2017: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/29191854/intended-vs-inferred-treatment-after-18f-fluoride-pet-performed-for-evaluation-of-osseous-metastatic-disease-in-the-national-oncologic-pet-registry
#6
Bruce E Hillner, Lucy Hanna, Rajesh Makineni, Fenghai Duan, Anthony F Shields, Rathan M Subramaniam, Ilana Gareen, Barry A Siegel
We have previously reported that PET with 18F-fluoride (NaF-PET) for assessment of osseous metastatic disease led to changes in intended management in a substantial fraction of patients with prostate or other types of cancer participating in the National Oncologic PET Registry (NOPR). This study was performed to assess the concordance of intended patient management after NaF-PET and inferred management based on analysis of Medicare claims. Methods: We analyzed linked post-PET data of consenting NOPR participants age > 65 years from 2011 to 2014 and their corresponding Medicare claims...
November 30, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/29188197/68ga-prostate-specific-membrane-antigen-positron-emission-tomography-computed-tomography-in-advanced-prostate-cancer-current-state-and-future-trends
#7
REVIEW
Cristian Udovicich, Marlon Perera, Michael S Hofman, Shankar Siva, Andres Del Rio, Declan G Murphy, Nathan Lawrentschuk
The early and accurate detection of prostate cancer is important to ensure timely management and appropriate individualized treatment. Currently, conventional imaging has limitations particularly in the early detection of metastases and at prostate-specific antigen (PSA) levels < 2.0 ng/mL. Furthermore, disease management such as salvage radiotherapy is best at low PSA levels. Thus, it is critical to capture the disease in the oligometastatic stage as disease progression and commencement of systemic therapies can be delayed by metastasis-directed therapy...
December 2017: Prostate International
https://www.readbyqxmd.com/read/29183960/radium-223-safety-efficacy-and-concurrent-use-with-abiraterone-or-enzalutamide-first-u-s-experience-from-an-expanded-access-program
#8
Oliver Sartor, Nicholas J Vogelzang, Christopher Sweeney, Daniel C Fernandez, Fabio Almeida, Andrei Iagaru, Alan Brown, Matthew R Smith, Manish Agrawal, Adam P Dicker, Jorge A Garcia, Jose Lutzky, Yu-Ning Wong, Oana Petrenciuc, Jeremy Gratt, Neal D Shore, Michael J Morris
BACKGROUND: In the phase III ALSYMPCA trial, metastatic castration-resistant prostate cancer (mCRPC) patients had few prior life-prolonging therapies. Following ALSYMPCA, which demonstrated radium-223 survival benefit, and before radium-223 U.S. commercial availability, an expanded access program (EAP) providing early-access radium-223 allowed life-prolonging therapies in current use. SUBJECTS, MATERIALS, AND METHODS: This phase II, open-label, single-arm, multicenter U...
November 28, 2017: Oncologist
https://www.readbyqxmd.com/read/29181271/radium-223-in-metastatic-hormone-sensitive-high-grade-prostate-cancer-initial-experience
#9
García-Pérez Francisco Osvaldo, Medina-Ornelas Sevastián Salvador, Santana-Ríos Zael, Sobrevilla-Moreno Nora
Our study evaluates the feasibility of compassionate exemption of Radium-223 (223Ra) treatment in metastatic hormone-sensitive high-grade prostate cancer (mHSHGPC) patients with concomitant androgen deprivation-therapy (ADT). Seven patients with mHSHGPC, were treated with six cycles of 223Ra plus ADT. All patients had undergone to 18F-NaF-PET/CT. A qualitative analyses of the 18F-NaF-PET/CT was performed in conjunction with Alkaline Phosphatase (ALP), Lactate-dehydrogenase (LDH) and Prostatic-Specific Antigen (PSA) values...
2017: American Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/29180633/integrating-evolutionary-dynamics-into-treatment-of-metastatic-castrate-resistant-prostate-cancer
#10
Jingsong Zhang, Jessica J Cunningham, Joel S Brown, Robert A Gatenby
Abiraterone treats metastatic castrate-resistant prostate cancer by inhibiting CYP17A, an enzyme for testosterone auto-production. With standard dosing, evolution of resistance with treatment failure (radiographic progression) occurs at a median of ~16.5 months. We hypothesize time to progression (TTP) could be increased by integrating evolutionary dynamics into therapy. We developed an evolutionary game theory model using Lotka-Volterra equations with three competing cancer "species": androgen dependent, androgen producing, and androgen independent...
November 28, 2017: Nature Communications
https://www.readbyqxmd.com/read/29173269/transrectal-ultrasound-guided-prostate-biopsies-vs-mri-ultrasound-fusion-targeted-biopsies-who-are-the-best-candidates
#11
Elsa Bey, Olivier Gaget, Jean-Luc Descotes, Quentin Franquet, Jean-Jacques Rambeaud, Jean-Alexandre Long, Gaelle Fiard
INTRODUCTION: The aim of this study was to compare the results of ultrasound-guided prostate biopsies (US-PB) and magnetic resonance imaging ultrasound fusion biopsies (MRI-PB) in two contemporary cohorts, and to describe the parameters orienting the choice of technique. METHODS: Two contemporary cohorts of patients undergoing US-PB or MR-PB using the Urostation® (Koelis, Grenoble, France) between November 2010 and July 2015 were analyzed retrospectively. Patients with metastatic cancer or recurrence after treatment, saturation biopsies, and US-PB performed after a negative MRI were excluded...
December 1, 2017: Canadian Urological Association Journal, Journal de L'Association des Urologues du Canada
https://www.readbyqxmd.com/read/29173266/testicular-oligometastasis-from-prostate-cancer-report-of-rare-isolated-recurrence-after-radiotherapy-and-intermittent-androgen-deprivation-therapy
#12
Chan-Kyung J Cho, Samantha Sigurdson, Christopher M Davidson, Michael Leveridge, Aamer Mahmud
Testicular oligometastasis secondary to prostate cancer is rare. We present a case where a patient with locally advanced prostate cancer was treated with high-dose external beam radiotherapy and two years of androgen-deprivation therapy, followed by intermittent androgen suppression. Three and a half years after initial diagnosis, he was found to have a painless testicular mass. Orchiectomy was performed and histopathology demonstrated metastatic prostatic adenocarcinoma. He remains in clinical remission on intermittent androgen suppression eight years following initial treatment, and over four years after presentation with testicular metastasis...
December 1, 2017: Canadian Urological Association Journal, Journal de L'Association des Urologues du Canada
https://www.readbyqxmd.com/read/29170762/clinical-utility-of-clia-grade-ar-v7-testing-in-patients-with-metastatic-castration-resistant-prostate-cancer
#13
Mark C Markowski, John L Silberstein, James R Eshleman, Mario A Eisenberger, Jun Luo, Emmanuel S Antonarakis
Purpose: A splice variant of the androgen receptor, AR-V7, confers resistance to AR-targeted therapies (ATTs) but not taxane chemotherapies in patients with metastatic castration-resistant prostate cancer. Since August 2015, a clinical-grade assay to detect AR-V7 messenger RNA expression in circulating tumors cells (CTCs) has been available to providers through a Clinical Laboratory Improvement Amendments-certified laboratory at Johns Hopkins University. Methods: We contacted ordering providers of the first 150 consecutive tests by using a questionnaire-based survey to determine how the results of AR-V7 testing were used to influence clinical practice...
2017: JCO Precision Oncology
https://www.readbyqxmd.com/read/29170516/metabolic-differences-in-glutamine-utilization-lead-to-metabolic-vulnerabilities-in-prostate-cancer
#14
Niki Marie Zacharias, Christopher McCullough, Sriram Shanmugavelandy, Jaehyuk Lee, Youngbok Lee, Prasanta Dutta, James McHenry, Linda Nguyen, William Norton, Lawrence W Jones, Pratip K Bhattacharya
The new oncologic paradigm of precision medicine is focused on identifying metabolic, proteomic, transcriptomic and genomic variabilities in tumors that can be exploited to tailor treatments and improve patient outcomes. Metabolic changes are a hallmark of cancer, and inhibition of metabolic pathways is now a major strategy in medicinal chemistry for targeting cancers. However, non-invasive biomarkers to categorize metabolic subtypes are in short supply. The purpose of this study was to characterize the intracellular and extracellular metabolic profiles of four prostate cancer cell lines with varying degrees of aggressiveness...
November 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29164346/impact-of-prior-androgen-receptor-axis-targeted-agents-on-the-clinical-activity-of-subsequent-docetaxel-in-patients-with-metastatic-castration-resistant-prostate-cancer-comparative-assessment-between-abiraterone-acetate-and-enzalutamide
#15
Hideaki Miyake, Yuto Matsushita, Keita Tamura, Daisuke Motoyama, Toshiki Ito, Takayuki Sugiyama, Atsushi Otsuka
The objective of this study was to investigate the impact of prior treatment with androgen receptor-axis-targeted (ARAT) agents, abiraterone acetate (AA) and enzalutamide (Enz), on the activity of subsequently introduced docetaxel in patients with metastatic castration-resistant prostate cancer (mCRPC). This study included a total of 114 mCRPC patients consisting of 54 and 60 who progressed following treatment with AA and Enz, respectively, prior to the introduction of docetaxel, and compared oncological outcomes with docetaxel between these two groups...
November 21, 2017: Medical Oncology
https://www.readbyqxmd.com/read/29162647/a-unifying-biology-of-sex-steroid-induced-apoptosis-in-prostate-and-breast-cancers
#16
Philipp Y Maximov, Balkees Abderrahman, Ramona F Curpan, Yousef A Hawsawi, Ping Fan, V Craig Jordan
Prostate and breast cancer are the two cancers with the highest incidence in men and women, respectively. Here we focus on the known biology of acquired resistance to antihormone therapy of prostate and breast cancer and compare laboratory and clinical similarities in the evolution of the disease. Laboratory studies and clinical observations in prostate and breast cancer demonstrate that cell selection pathways occur during acquired resistance to antihormonal therapy. Following sex steroid deprivation, both prostate and breast cancer models show an initial increased acquired sensitivity to the growth potential of sex steroids...
November 21, 2017: Endocrine-related Cancer
https://www.readbyqxmd.com/read/29161337/age-at-diagnosis-and-prostate-cancer-treatment-and-prognosis-a-population-based-cohort-study
#17
A Pettersson, D Robinson, H Garmo, L Holmberg, P Stattin
Background: Old age at prostate cancer diagnosis has been associated with poor prognosis in several studies. We aimed to investigate the association between age at diagnosis and prognosis, and if it is independent of tumor characteristics, primary treatment, year of diagnosis, mode of detection and comorbidity. Patients and methods: We conducted a nation-wide cohort study including 121,392 Swedish men aged 55-95 years in Prostate Cancer data Base Sweden (PCBaSe) 3...
November 17, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29156772/stat3-and-stat5a-are-potential-therapeutic-targets-in-castration-resistant-prostate-cancer
#18
Sambit K Mohanty, Kader Yagiz, Dinesh Pradhan, Daniel J Luthringer, Mahul B Amin, Serhan Alkan, Bekir Cinar
Mechanisms of castration-resistant prostate cancer (CRPC) are not well understood, thus hindering rational-based drug design. Activation of STAT3/5A, key components of the JAK/STAT pathway, is implicated in aggressive PC, yet their clinical relevance in CRPC remains elusive. Here, we evaluated the possible role of STAT3/5A in CRPC using immunological, quantitative mRNA expression profiling, and pharmacological methods. We observed a strong nuclear immunoreactivity for STAT3 and STAT5A in 93% (n=14/15) and 80% (n=12/15) of CRPC cases, respectively, compared with benign prostatic hyperplasia (BPH)...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29153623/abiraterone-acetate-prednisolone-treatment-beyond-prostate-specific-antigen-and-radiographic-progression-in-metastatic-castration-resistant-prostate-cancer-patients
#19
Krisztina Biró, Barna Budai, Márta Szőnyi, Zsófia Küronya, Fruzsina Gyergyay, Krisztián Nagyiványi, Lajos Géczi
OBJECTIVES: To investigate the overall survival (OS) of chemotherapy refractory patients with metastatic castration-resistant prostate cancer who were treated with abiraterone acetate + prednisolone (AA + P) beyond prostate specific antigen (PSA) and radiographic progression (PRP) until clinical progression in comparison to patients treated until PRP. METHODS: At our institute the AA + P treatment started in 2011 in an early-access protocol trial. In October 2012 AA became generally available...
November 15, 2017: Urologic Oncology
https://www.readbyqxmd.com/read/29152128/modulation-of-cabozantinib-efficacy-by-the-prostate-tumor-microenvironment
#20
Manisha Tripathi, Srinivas Nandana, Sandrine Billet, Karen A Cavassani, Rajeev Mishra, Leland W K Chung, Edwin M Posadas, Neil A Bhowmick
The tumor microenvironment (TME) is increasingly recognized as the arbiter of metastatic progression and drug resistance in advanced prostate cancer (PCa). Cabozantinib is a potent tyrosine kinase inhibitor (TKI) with reported biological activity in the PCa epithelia, but failed to provide an overall survival benefit in phase 3 clinical trials. However, the promising biologic efficacy of the drug in early trials warranted a better understanding of the mechanism of action, with the goal of improving patient selection for TKI-based therapy such as cabozantinib...
October 20, 2017: Oncotarget
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