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Androgen deprivation therapy

Mohit Kumar Jolly, Prakash Kulkarni, Keith Weninger, John Orban, Herbert Levine
It is well known that genetic mutations can drive drug resistance and lead to tumor relapse. Here, we focus on alternate mechanisms-those without mutations, such as phenotypic plasticity and stochastic cell-to-cell variability that can also evade drug attacks by giving rise to drug-tolerant persisters. The phenomenon of persistence has been well-studied in bacteria and has also recently garnered attention in cancer. We draw a parallel between bacterial persistence and resistance against androgen deprivation therapy in prostate cancer (PCa), the primary standard care for metastatic disease...
2018: Frontiers in Oncology
Satoru Ueno, Yasuhide Kitagawa, Mizuki Onozawa, Shiro Hinotsu, Hideyuki Akaza, Atsushi Mizokami, Mikio Namiki
Background: This prospective observational study elucidated the usefulness of hormonal therapy for localized prostate cancer. Background factors and the health-related quality of life in patients who initially underwent radical prostatectomy (RP) or primary androgen deprivation therapy (PADT) for localized prostate cancer are summarized. Materials and methods: Patients aged 67-76 years with clinical stage T1c or T2 localized prostate cancer treated with PADT or RP, a prostate-specific antigen concentration of <20 ng/mL, and Gleason score of ≤7 were included...
March 2018: Prostate International
Sonja Cabarkapa, Marlon Perera, Ken Sikaris, Jonathan S O'Brien, Damien M Bolton, Nathan Lawrentschuk
Background: This study aims to review current laboratory reporting strategies across Australia and New Zealand with a view to propose a more useful template for reporting serum testosterone in the context of prostate cancer. Materials and methods: Registered pathology laboratories in Australia and New Zealand were enrolled into the current study. An electronic or a phone survey was utilized to collect data from each participating laboratory. Obtained information included assay utilized, units reported, reference intervals, lowest reported value, and lowest detectable value...
March 2018: Prostate International
Benjamin Benzon, Stephanie A Glavaris, Brian W Simons, Robert M Hughes, Kamyar Ghabili, Patrick Mullane, Rebecca Miller, Katriana Nugent, Brian Shinder, Jeffrey Tosoian, Ephraim J Fuchs, Phuoc T Tran, Paula J Hurley, Milena Vuica-Ross, Edward M Schaeffer, Charles G Drake, Ashley E Ross
BACKGROUND: Prostate cancer remains the second leading cause of cancer related death in men. Immune check point blocking antibodies have revolutionized treatment of multiple solid tumors, but results in prostate cancer remain marginal. Previous reports have suggested that local therapies, in particular cryoablation might increase tumor immunogenicity. In this work, we examine potential synergism between tumor cryoabalation and check point blocking antibodies. METHODS: FVB/NJ mice were injected subcutaneously into each flank with either 1 × 106 or 0...
March 20, 2018: Prostate Cancer and Prostatic Diseases
J M Cozar, I Robles-Fernandez, L J Martinez-Gonzalez, M Pascual-Geler, Alba Rodriguez-Martinez, M J Serrano, J A Lorente, M J Alvarez-Cubero
Prostate cancer (PC) is one of the most common cancers worldwide. The observed variability in progression and responses to the same treatment between patients underlie the genetic heterogeneity of the disease. Nowadays, screening and follow-up biomarkers in PC are still having a deep lack of information, which makes difficult the cancer diagnosis, prognosis and the selection of the most suitable therapies. This is making that currently unnecessary biopsies, over-treatments and hormonoresistances have high rates of prevalence among patients...
January 2018: Mutation Research
Luke C Peng, Amol K Narang, Carol Gergis, Noura A Radwan, Peijin Han, Ariel E Marciscano, Scott P Robertson, Pei He, Janson Trieu, Ashwin N Ram, Todd R McNutt, Emily Griffith, Theodore A DeWeese, Stephanie Honig, Harleen Singh, Stephen C Greco, Phuoc T Tran, Curtiland Deville, Theodore L DeWeese, Daniel Y Song
OBJECTIVES: Perineural invasion (PNI) has not yet gained universal acceptance as an independent predictor of adverse outcomes for prostate cancer treated with external beam radiotherapy (EBRT). We analyzed the prognostic influence of PNI for a large institutional cohort of prostate cancer patients who underwent EBRT with and without androgen deprivation therapy (ADT). MATERIAL AND METHODS: We, retrospectively, reviewed prostate cancer patients treated with EBRT from 1993 to 2007 at our institution...
March 15, 2018: Urologic Oncology
Antoine Angelergues, Eleni Efstathiou, Revekka Gyftaki, Piotr Jan Wysocki, Nuria Lainez, Iria Gonzalez, Daniel E Castellano, Mustafa Ozguroglu, Iciar Garcia Carbonero, Aude Flechon, Pablo Borrega, Aline Guillot, Begona Campos Balea, Sylvestre Le Moulec, Emilio Esteban, Javier Munarriz, Gustavo Rubio, Alison J Birtle, Nicolas Delanoy, Joaquim Bellmunt, Stéphane Oudard
BACKGROUND: Several agents have demonstrated an overall survival (OS) benefit in patients with metastatic castration-resistant prostate cancer (mCRPC); however, the optimal sequencing of these therapies is unknown as a result of a lack of prospective randomized controlled trials. This retrospective study aimed to identify clinical factors influencing outcomes and to determine optimal treatment sequencing in patients with mCRPC treated with cabazitaxel (CABA) and/or androgen receptor-targeted agents (ART) after androgen-deprivation therapy (ADT) and docetaxel (DOC)...
February 23, 2018: Clinical Genitourinary Cancer
Nicholas Russell, Rudolf Hoermann, Ada S Cheung, Michael Ching, Jd Zajac, David J Handelsman, Mathis Grossmann
OBJECTIVE: There is increasing recognition that, in men, some biological actions attributed to testosterone (T) are mediated by estradiol (E2). This study used two low doses of daily transdermal E2 gel to assess effects on circulating E2 concentrations in men with prostate cancer with suppressed endogenous E2 production arising from androgen deprivation therapy (ADT). Secondarily, we aimed to assess short term biological effects of E2 addback without increasing circulating T. DESIGN: 28-day randomised, placebo-controlled trial Methods: 37 participants were randomised to either 0...
March 16, 2018: European Journal of Endocrinology
Jun Hao, Xinpei Ci, Hui Xue, Rebecca Wu, Xin Dong, Stephen Yiu Chuen Choi, Haiqing He, Yu Wang, Fang Zhang, Sifeng Qu, Fan Zhang, Anne M Haegert, Peter W Gout, Amina Zoubeidi, Colin Collins, Martin E Gleave, Dong Lin, Yuzhuo Wang
BACKGROUND: Although androgen deprivation therapy is initially effective in controlling growth of hormone-naive prostate cancers (HNPCs) in patients, currently incurable castration-resistant prostate cancer (CRPC) inevitably develops. OBJECTIVE: To identify CRPC driver genes that may provide new targets to enhance CRPC therapy. DESIGN, SETTING, AND PARTICIPANTS: Patient-derived xenografts (PDXs) of HNPCs that develop CRPC following host castration were examined for changes in expression of genes at various time points after castration using transcriptome profiling analysis; particular attention was given to pre-CRPC changes in expression indicative of genes acting as potential CRPC drivers...
March 12, 2018: European Urology
Munveer S Bhangoo, Brian Cheng, Gregory P Botta, Phataraporn Thorson, Michael P Kosty
As with other genitourinary malignancies, a variety of paraneoplastic syndromes have been revealed to occur in patients with prostate cancer. Stauffer's Syndrome is a well-described clinical syndrome which manifests via intrahepatic cholestasis in patients with renal cell carcinoma. Less common is intrahepatic cholestasis occurring in association with prostate cancer. The current case report discusses a 67-year-old man presenting with liver failure secondary to intrahepatic cholestasis co-existing with metastatic prostate adenocarcinoma...
April 2018: Molecular and Clinical Oncology
Michael V Fiandalo, John J Stocking, Elena A Pop, John H Wilton, Krystin M Mantione, Yun Li, Kristopher M Attwood, Gissou Azabdaftari, Yue Wu, David S Watt, Elizabeth M Wilson, James L Mohler
Androgen deprivation therapy (ADT) is palliative and prostate cancer (CaP) recurs as lethal castration-recurrent/resistant CaP (CRPC). One mechanism that provides CaP resistance to ADT is primary backdoor androgen metabolism, which uses up to four 3α-oxidoreductases to convert 5α-androstane-3α,17β-diol (DIOL) to dihydrotestosterone (DHT). The goal was to determine whether inhibition of 3α-oxidoreductase activity decreased conversion of DIOL to DHT. Protein sequence analysis showed that the four 3α-oxidoreductases have identical catalytic amino acid residues...
February 16, 2018: Oncotarget
L Klotz, A Loblaw, R Siemens, P Ouellette, A Kapoor, M Kebabdjian, L Zhang, F Saad
BACKGROUND: In men initiating intermittent androgen deprivation therapy (IADT), a range of induction durations, between 3 and 12 months, have been employed. OBJECTIVE: To determine if the duration of induction ADT influences the duration of the off treatment interval and the recovery of serum testosterone (T). MANEUVER: This was a prospective, randomized, open label study. Men with biochemical recurrence after local therapy for prostate cancer, with a negative bone scan, were randomized between 4 and 10 months of monthly Degarelix...
March 10, 2018: Journal of Urology
Derek S Tsang, Jennifer M Jones, Osai Samadi, Suhayb Shah, Nicholas Mitsakakis, Charles N Catton, William Jeon, Joshua To, Henriette Breunis, Shabbir M H Alibhai
PURPOSE: To evaluate the ability of a multimodal patient education initiative to improve adherence to healthy bone behaviors (HBBs) in men with prostate cancer receiving androgen deprivation therapy (ADT). METHODS: This was a pilot prospective, single-site, before-and-after clinical trial. The control arm (n = 51) received routine care. The intervention arm (n = 52) received multimodal HBB education which included a healthy bones prescription (BoneRx), focused face-to-face education with an oncology nurse or physician, and customized educational materials...
March 12, 2018: Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer
Margaret M Centenera, Luke A Selth, Esmaeil Ebrahimie, Lisa M Butler, Wayne D Tilley
Recent genomic analyses of metastatic prostate cancer have provided important insight into adaptive changes in androgen receptor (AR) signaling that underpin resistance to androgen deprivation therapies. Novel strategies are required to circumvent these AR-mediated resistance mechanisms and thereby improve prostate cancer survival. In this review, we present a summary of AR structure and function and discuss mechanisms of AR-mediated therapy resistance that represent important areas of focus for the development of new therapies...
March 12, 2018: Cold Spring Harbor Perspectives in Medicine
T Steuber, C Jilg, P Tennstedt, A De Bruycker, Derya Tilki, K Decaestecker, T Zilli, B A Jereczek-Fossa, U Wetterauer, A L Grosu, W Schultze-Seemann, H Heinzer, M Graefen, A Morlacco, R J Karnes, Piet Ost
BACKGROUND: Most prostate cancer (PCa) patients with a biochemical failure following primary multimodality treatment (surgery and postoperative radiotherapy) relapse in the nodes. OBJECTIVE: To perform a matched-case analysis in men with lymph node recurrent PCa comparing standard of care (SOC) with metastasis-directed therapy (MDT). DESIGN, SETTING, AND PARTICIPANTS: PCa patients with a prostate-specific antigen (PSA) progression following multimodality treatment were included in this retrospective multi-institutional analysis...
March 10, 2018: European Urology Focus
Matthew R Sydes, Melissa R Spears, Malcolm D Mason, Noel W Clarke, David P Dearnaley, Johann S de Bono, Gert Attard, Simon Chowdhury, Bill Cross, Silke Gillessen, Zaf Malik, Rob Jones, Chris Parker, Alastair W S Ritchie, J Martin Russell, Robin Millman, David Matheson, Claire Amos, Clare Gilson, Alison Birtle, Susannah Brock, Lisa Capaldi, Prabir Chakraborti, Ananya Choudhury, Linda Evans, Daniel Ford, Joanna Gale, Stephanie Gibbs, Duncan Gilbert, Robert Hughes, Duncan McLaren, Jason Lester, Ashok Nikapota, Joe O'Sullivan, Omi Parikh, Clive Peedell, Andrew Protheroe, Sarah M Rudman, Richard Shaffer, Denise Sheehan, Matthew Simms, Narayanan Srihari, Räto Strebel, Santhanam Sundar, Shaun Tolan, David Tsang, Mohini Varughese, John Wagstaff, Mahesh K B Parmar, Nicholas D James
Background: Adding abiraterone acetate with prednisolone (AAP) or docetaxel with prednisolone (DocP) to standard-of-care (SOC) each improved survival in STAMPEDE: a multi-arm multi-stage platform randomised controlled protocol recruiting patients with high-risk locally advanced or metastatic PCa starting long-term androgen deprivation therapy (ADT). The protocol provides the only direct, randomised comparative data of SOC+AAP vs SOC+DocP. Method: Recruitment to SOC+DocP and SOC+AAP overlapped Nov-2011─Mar-2013...
February 26, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
Matthew Utter, Sohag Chakraborty, Limor Goren, Lucas Feuser, Yuan-Shan Zhu, David A Foster
Prostate cells are hormonally driven to grow and divide. Typical treatments for prostate cancer involve blocking activation of the androgen receptor by androgens. Androgen deprivation therapy can lead to the selection of cancer cells that grow and divide independently of androgen receptor activation. Prostate cancer cells that are insensitive to androgens commonly display metastatic phenotypes and reduced long-term survival of patients. In this study we provide evidence that androgen-insensitive prostate cancer cells have elevated PLD activity relative to the androgen-sensitive prostate cancer cells...
March 7, 2018: Cancer Letters
Myong Kim, Cheryn Song, In Gab Jeong, Seung-Kwon Choi, Myungchan Park, Myungsun Shim, Young Seok Kim, Dalsan You, Jun Hyuk Hong, Choung-Soo Kim, Hanjong Ahn
BACKGROUND: Here we assessed the influence of androgen deprivation therapy (ADT) during and/or after post-prostatectomy radiotherapy (RT) on biochemical recurrence (BCR) and radiographic progression in patients with prostate cancer. METHODS: Patients with prostate cancer who underwent post-prostatectomy RT were analyzed. BCR and radiographic progression after RT were compared according to the concurrent or salvage ADT. Cox regression analyses were used to identify risk factors for BCR and radiographic progression...
March 9, 2018: BMC Cancer
Alicia K Morgans, Yu-Hui Chen, Christopher J Sweeney, David F Jarrard, Elizabeth R Plimack, Benjamin A Gartrell, Michael A Carducci, Maha Hussain, Jorge A Garcia, David Cella, Robert S DiPaola, Linda J Patrick-Miller
Purpose Chemohormonal therapy with docetaxel and androgen deprivation therapy (ADT+D) for metastatic hormone-sensitive prostate cancer improves overall survival as compared with androgen deprivation therapy (ADT) alone. We compared the quality of life (QOL) between patients with metastatic hormone-sensitive prostate cancer who were treated with ADT+D and those who were treated with ADT alone. Methods Men were randomly assigned to ADT+ D (six cycles) or to ADT alone. QOL was assessed by Functional Assessment of Cancer Therapy-Prostate (FACT-P), FACT-Taxane, Functional Assessment of Chronic Illness Therapy-Fatigue, and the Brief Pain Inventory at baseline and at 3, 6, 9, and 12 months...
March 9, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Alessandro Magli, Eugenia Moretti, Annarita Tullio, Gianluca Giannarini, Fabrizio Tonetto, Mauro Urpis, Margherita Crespi, Claudio Foti, Agnese Prisco, Margherita Polsinelli, Gioacchino De Giorgi, Giulia Bravo, Paolo Scalchi, Marco Trovò
OBJECTIVE: The approach for treating high-risk prostate cancer still presents different unresolved issues. We report the safety and efficacy of a radiation therapy strategy based on the combination of moderate hypofractioned simultaneous integrated boost (SIB) and Image Guidance. MATERIALS AND METHODS: In this phase II trial of patients with high-risk prostate cancer, Image Guided SIB-IMRT plans (Simultaneous Intensity Modulated - Intensity Modulated Radiotherapy) were delivered between 2009 and 2012...
March 8, 2018: Prostate Cancer and Prostatic Diseases
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