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Hormone sensitive prostate cancer

Emmanuel S Antonarakis, Farah Shaukat, Pedro Isaacsson Velho, Harsimar Kaur, Eugene Shenderov, Drew M Pardoll, Tamara L Lotan
Mismatch repair (MMR) gene mutations are rare in prostate cancer, and their histological and clinical characteristics are largely unknown. We conducted a retrospective study to explore disease characteristics and treatment outcomes of men with metastatic prostate cancer harboring germline and/or somatic MMR mutations detected using clinical-grade genomic assays. Thirteen patients with a deleterious MMR gene mutation were identified. Median age was 64 yr, 75% had grade group 5 (Gleason sum 9 or 10), 23% had intraductal histology, 46% had metastatic disease at initial diagnosis, and 31% had visceral metastases...
October 15, 2018: European Urology
Niranjan J Sathianathen, Yiannis A Philippou, Gretchen M Kuntz, Badrinath R Konety, Shilpa Gupta, Alastair D Lamb, Philipp Dahm
BACKGROUND: There has been considerable development in the treatment of advanced prostate cancer over the last decade. A number of agents, including docetaxel, cabazitaxel, abiraterone acetate, enzalutamide and sipuleucel-T, have been reported to improve outcomes in men with castration-resistant disease and their use is being explored in hormone-sensitive prostate cancer. OBJECTIVES: To assess the effects of early taxane-based chemohormonal therapy for newly diagnosed, metastatic, hormone-sensitive prostate cancer...
October 15, 2018: Cochrane Database of Systematic Reviews
Bogdan Mitran, Ken Gösta Andersson, Elin Lindström, Javad Garousi, Maria Rosestedt, Vladimir Tolmachev, Stefan Ståhl, Anna Orlova, John Löfblom
The epidermal growth factor receptor (EGFR) is often overexpressed during prostate cancer (PCa) progression towards androgen‑independence after hormone therapy, but the overexpression is lower than in other types of cancers. Despite the low expression, EGFR has emerged as a promising therapeutic target for patients with castration‑resistant PCa. Non‑invasive methods for determination of EGFR expression in PCa can serve for patient stratification and therapy response monitoring. Radionuclide imaging probes based on affibody molecules (7 kDa) provide high contrast imaging of cancer‑associated molecular targets...
October 15, 2018: Oncology Reports
Dipti Gupta, Katherine Lee Chuy, Ji Can Yang, Megan Bates, Marissa Lombardo, Richard M Steingart
Androgen-deprivation therapy (ADT) entails lowering serum testosterone levels to castrate levels and forms a cornerstone of the management of hormone-sensitive advanced prostate cancer; however, the benefit of ADT is partially offset by its detrimental metabolic and cardiovascular adverse effects. ADT decreases insulin sensitivity while promoting dyslipidemia and sarcopenic obesity, which leads to an increased risk of cardiovascular morbidity and potentially mortality. The risk seems to be highest in elderly patients who have had recent cardiovascular events before starting ADT...
October 2018: Journal of Oncology Practice
Giulia Baciarello, Marco Gizzi, Karim Fizazi
Prostate cancer is the second most common cause of cancer worldwide and is the most frequently detected cancer in the European Union in men over 50 years of age. Androgen deprivation therapy remains the cornerstone of treatment for recurrent or metastatic disease. Unfortunately, nearly all patients will develop resistance to androgen blockade leading to castration-resistant prostate cancer (CRPC). Over the last 10 years, new treatments have dramatically improved overall survival of men with mCRPC. Current therapies are based on AR-axis inhibitors and taxane-based chemotherapies, as well as radiopharmaceuticals and Sipuleucel T...
October 12, 2018: Expert Opinion on Pharmacotherapy
Zsófia Küronya, Krisztina Bíró, Lajos Géczi, Anikó Maráz
The treatment of metastatic prostate cancer can be divided into two pathophysiological phases: hormone-sensitive and castration-resistant phases. Huggins' observation in the year 1941, which was awarded with the Nobel Prize in 1966, has a key role in treatment during the hormone-sensitive phase, stating that if the testicles are removed, the size of the prostate cancer decreases. Inducing androgen deprivation, i.e., testosterone depletion is the basic treatment of metastatic prostate cancer that patients have to receive life-long...
October 2018: Orvosi Hetilap
Igor Tsaur, Isabel Heidegger, Alexander Kretschmer, Hendrik Borgmann, Cristian Mirvald, Giorgio Gandaglia, Alberto Briganti, Roderick van den Bergh, Derya Tilki, Piet Ost, Guillaume Ploussard, Cristian Surcel
Recently, a plethora of life-prolonging cytotoxic, next-generation hormonal, immunotherapeutical as well as radionuclide therapies has emerged as a standard care for metastasized castration-resistant prostate cancer. Being strikingly effective in cancer control, these novel therapies might in fact exert a beneficial impact on skeletal events. Therefore, combining anticancer drugs with osteoprotective agents might lead to additional clinical advantage but must be weighed against simultaneously exposing patients to serious toxicities...
September 26, 2018: Urologic Oncology
Theodore S Thomas, Russell K Pachynski
Advanced prostate cancer is a heterogenous disease with multiple treatment options. Patients with advanced disease are stratified based evidence of metastasis and sensitivity to hormone therapy. Men with hormone sensitive disease are treated with androgen deprivation therapy and possibly chemotherapy. The treatment options for men with castrate resistant disease are rapidly evolving with multiple recently approved treatment options. Determining the proper sequence and combination of these therapies remains a work in progress...
March 2018: Missouri Medicine
Helle D Zacho, Lars J Petersen
A 69-year-old man with newly diagnosed prostate cancer PSA 274 ng/mL, Gleason 4+3, T-stage 3b) underwent Ga-PSMA PET/CT for staging with follow-up scans 6 and 13 weeks after androgen deprivation therapy (ADT) initiation. Six weeks after ADT initiation, lymph node metastases observed at staging showed metabolic and radiological regression, whereas the skeleton showed increased PSMA uptake in existing bone metastases and several new PSMA-avid lesions. Skeletal PSMA uptake decreased after 13 weeks of ADT, and prostate-specific antigen decreased to 16 ng/mL...
November 2018: Clinical Nuclear Medicine
Susan Feyerabend, Fred Saad, Tracy Li, Tetsuro Ito, Joris Diels, Suzy Van Sanden, Peter De Porre, Julie Roiz, Seye Abogunrin, Maria Koufopoulou, Karim Fizazi
AIM: Androgen deprivation therapy (ADT) has long been the gold standard for patients with metastatic hormone-sensitive prostate cancer (mHSPC). Clinical trials have demonstrated significant survival benefits when docetaxel (DOC) or abiraterone acetate (AA) and prednisone (P) are added to ADT, necessitating comparison of these combination treatments. METHODS: A systematic review of randomised controlled trials (RCTs) of AA-/ADT-/DOC-containing treatment regimens in newly diagnosed patients with high-risk and/or high-volume mHSPC identified three RCTs (LATITUDE, CHAARTED and GETUG-AFU 15)...
September 12, 2018: European Journal of Cancer
Karim Fizazi, Matthew R Smith, Bertrand Tombal
Prostate cancer (PC) is the second most common cancer in men and is the fifth leading cause of cancer-related deaths among men. Androgen receptor (AR) signaling plays a key role in PC tumor growth and progression, with androgens stimulating PC proliferation and survival. Castration-resistant PC (CRPC) is characterized by increasing levels of prostate-specific antigen or radiographic progression despite androgen-deprivation therapy (ADT). In most patients, castration resistance results from aberrations in AR or the AR signaling pathway...
July 24, 2018: Clinical Genitourinary Cancer
Neil M Schultz, Scott C Flanders, Samuel Wilson, Bruce A Brown, Yan Song, Hongbo Yang, Stanislav Lechpammer, Vahan Kassabian
INTRODUCTION: Enzalutamide and abiraterone acetate (plus prednisone) are new hormonal treatments for metastatic castration-resistant prostate cancer (mCRPC). This study compared treatment duration, healthcare resource utilization (HRU), and treatment costs for chemotherapy-naïve mCRPC patients treated with enzalutamide or abiraterone acetate in the USA. METHODS: Chemotherapy-naïve mCRPC patients initiating treatment with enzalutamide or abiraterone acetate were identified from administrative claims...
October 2018: Advances in Therapy
C Leigh Moyer, Ryan Phillips, Matthew P Deek, Noura Radwan, Ashley E Ross, Emmanuel S Antonarakis, Diane Reyes, Jean Wright, Stephanie A Terezakis, Daniel Y Song, Curtiland DeVille, Patrick C Walsh, Theodore L DeWeese, Michael Carducci, Edward M Schaeffer, Kenneth J Pienta, Mario Eisenberger, Phuoc T Tran
PURPOSE: Local ablative treatment to oligometastatic patients can result in long-term disease-free survival in some cancer patients. The importance of this treatment paradigm in prostate cancer is a rapidly evolving field. Herein, we report on the safety and preliminary clinical outcomes of a modern cohort of oligometastatic prostate cancer (OPC) patients treated with consolidative stereotactic ablative radiation (SABR). METHODS: Records of men with OPC who underwent consolidative SABR at our institution were reviewed...
September 6, 2018: World Journal of Urology
Nicholas D James
No abstract text is available yet for this article.
September 2018: BJU International
Kyoung-Hwa Lee, Seokbong Hong, Minyong Kang, Chang Wook Jeong, Ja Hyeon Ku, Hyeon-Hoe Kim, Cheol Kwak
Prostate cancer can be controlled by androgen-hormone treatment until the cancer becomes refractory. It is believed that hormone sensitivity is largely dependent on androgen receptor (AR) activity. Here, we found the histone demethylase KDM7A which demethylates histone H3K27 to be overexpressed in enzalutamide resistant castration-resistant prostate cancer cell line C4-2b, and investigated the molecular mechanism whereby androgen receptor activity is regulated by KDM7A. We engineered AR-positive LNCaP cells to stably express a short-hairpin RNA against KDM7A mRNA from a lentiviral vector...
September 5, 2018: International Journal of Cancer. Journal International du Cancer
Roberto Iacovelli, Chiara Ciccarese, Claudia Mosillo, Davide Bimbatti, Emanuela Fantinel, Lisa Stefani, Michele Simbolo, Mario Romano, Renzo Mazzarotto, Matteo Brunelli, Emilio Bria, Aldo Scarpa, Rita T Lawlor, Walter Artibani, Giampaolo Tortora
BACKGROUND: The CHAARTED and LATITUDE trials demonstrated improved outcomes with docetaxel or abiraterone plus androgen deprivation therapy in metastatic hormone sensitive prostate cancer (mHSPC) using two different prognostic scores. OBJECTIVE: The aim of our study was to assess the concordance between the two scores and if these retained their prognostic value exclusively in de novo mHSPC. PATIENTS AND METHODS: De novo mHSPC patients referring to our institution were retrospectively stratified according to the CHAARTED and LATITUDE classifications: high volume/high risk (HV/HR), low-volume/low-risk (LV/LR), and HVorHR (HV/LR and LV/HR)...
October 2018: Targeted Oncology
Nicholas E Brown, Andrew M Paluch, Madison A Nashu, Kakajan Komurov, Susan E Waltz
Current treatment strategies provide minimal results for patients with castration-resistant prostate cancer (CRPC). Attempts to target the androgen receptor have shown promise, but resistance ultimately develops, often due to androgen receptor reactivation. Understanding mechanisms of resistance, including androgen receptor reactivation, is crucial for development of more efficacious CRPC therapies. Here, we report that the RON receptor tyrosine kinase is highly expressed in the majority of human hormone-refractory prostate cancers...
September 2018: Neoplasia: An International Journal for Oncology Research
Stefan Aufderklamm, Jörg Hennenlotter, Phillip Leidenberger, Steffen Rausch, Andrea Hohneder, Ursula Kühs, Moritz Maas, Christian Schwentner, Jens Bedke, Arnulf Stenzl, Tilman Todenhöfer
Purpose: Dickkopf-1 (DKK-1) and sclerostin seem to inhibit osteoblast activity by blocking the Wnt pathway, which leads to progression of metastatic prostate cancer (PC). However, it is unknown whether serum levels of these proteins are altered in PC patients with or without metastasis. The aim of this study was to assess DKK-1 and sclerostin serum levels in PC patients, including patients with bone metastases. Methods: The study cohort ( N = 143) consisted of 53 controls with benign prostatic hyperplasia (BPH), 43 with localized PC (PC cM0), and 47 had PC with metastasis (PC cM1)...
2018: Disease Markers
Rafael Sebastián Fort, Juan M Trinidad Barnech, Juliette Dourron, Marcos Colazzo, Francisco J Aguirre-Crespo, María Ana Duhagon, Guzmán Álvarez
Prostate cancer is the most common cancer in men around the world. It is a complex and heterogeneous disease in which androgens and their receptors play a crucial role in the progression and development. The current treatment for prostate cancer is a combination of surgery, hormone therapy, radiation and chemotherapy. Therapeutic agents commonly used in the clinic include steroidal and non-steroidal anti-androgens, such as cyproterone acetate, bicalutamide and enzalutamide. These few agents have multiple adverse effects and are not 100% effective...
August 14, 2018: Pharmaceuticals
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