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Metastatic hormone sensitive prostate cancer

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
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
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
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
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
Lai Xu, Russell K Pachynski
PURPOSE OF REVIEW: Androgen deprivation therapy (ADT) has been the standard-of-care (SOC) for metastatic hormone-sensitive prostate cancer (mHSPC) since the middle of the twentieth century. Recently, several practice-changing trials have added new therapy options for these patients. Here we review these studies and discuss guidelines on treatment decision-making. RECENT FINDINGS: A trio of studies (GETUG-AFU15, STAMPEDE, CHAARTED) combining docetaxel chemotherapy with ADT all showed clinical benefit of the addition...
August 13, 2018: Current Urology Reports
Charlotte Fenioux, Christophe Louvet, Emilie Charton, Francois Rozet, Stanislas Ropert, Dominique Prapotnich, Eric Barret, Rafael Sanchez-Salas, Annick Mombet, Nathalie Cathala, Marie-Liesse Joulia, Jean-Luc Molitor, Julie Henriques, Franck Bonnetain, Xavier Cathelineau, Mostefa Bennamoun
OBJECTIVE: To evaluate the effects of switching from prednisone (P) to dexamethasone (D) at asymptomatic prostate-specific antigen (PSA) progression in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with abiraterone acetate (AA). MATERIALS AND METHODS: Among 93 patients treated with AA between January 2013 and April 2016 in our institution, 48 consecutive asymptomatic patients with mCRPC, who experienced biochemical progression on treatment with AA+P 10 mg/day, were included...
August 11, 2018: BJU International
Omar Abdel-Rahman, Winson Y Cheung
BACKGROUND: Local treatment of metastatic prostate cancer and its impact on future disease course requires further assessment. We sought to evaluate the impact of prior local treatment to the prostate on the outcomes of hormone-sensitive prostate cancer (HSPC) patients recruited in the CHAARTED study. PATIENTS AND METHODS: We performed a retrospective analysis of the prospectively collected data among patients with metastatic HSPC in the CHAARTED study, a phase 3 multicenter study conducted between 2006 and 2014...
July 21, 2018: Clinical Genitourinary Cancer
Charles C Vu, Kevin G Blas, Thomas B Lanni, Gary S Gustafson, Daniel J Krauss
PURPOSE: The recently published ASCENDE-RT randomized clinical trial demonstrated improved biochemical control, albeit with increased toxicity, for a prostate boost with brachytherapy versus external beam radiation therapy alone in patients with intermediate-high risk prostate cancer. In this study, we investigated the cost-effectiveness of these two modalities in the treatment of intermediate-high risk prostate cancer. METHODS AND MATERIALS: A multistate Markov model was created to model a patient with intermediate-high risk prostate cancer...
July 31, 2018: Brachytherapy
Oliver Sartor, Deepali Sharma
223 Radium (223 Ra) is the first alpha-emitting therapy proven effective in human cancer. Prospective randomized trials indicate that 223 Ra, which concentrates after intravenous injection in areas of osteoblastic metastatic disease, can prolong survival in bone-dominant castrate resistant prostate cancer patients. Though radium isotopic therapy is conceptually critical to demonstrate that alpha emitters can be safe and effective, 223 Ra has inherent limitations given its restriction to bone metastatic disease...
June 2018: Translational Andrology and Urology
Aditya Prakash Sharma, Ravimohan S Mavuduru, Girdhar Singh Bora, Sudheer K Devana, Shrawan K Singh, Arup K Mandal
With the emergence of recent landmark trials, the treatment for hormone-sensitive metastatic prostate cancer (hsMPC) is changing from androgen deprivation therapy (ADT) alone to combination therapy. Both, docetaxel chemotherapy and abiraterone in addition to ADT have been extensively studied in well-conducted randomized controlled trials and were shown to improve outcomes. However, this paradigm shift in the treatment has also raised some queries. This mini review reflects upon the four landmark trials and tries to provide some perspective about the decision-making process for the patients with hsMPC...
July 2018: Indian Journal of Urology: IJU: Journal of the Urological Society of India
K Miller
No abstract text is available yet for this article.
August 2018: Der Urologe. Ausg. A
Hongtuan Zhang, Zhenpeng Lian, Guangyu Sun, Ranlu Liu, Yong Xu
To gain a comprehensive understanding of whether ABCC5 can regulate prostate cancer (PCa) progression, we performed microarray data analyses and identified that ABCC5 was drastically increased in primary PCa relative to normal samples, metastatic PCa relative to primary PCa, and castration-resistant PCa relative to hormone naïve PCa, respectively. Multivariate Cox regression analysis suggested that ABCC5 overexpression in PCa was an independent prognostic factor for both poor biochemical recurrence-free and overall survival...
2018: OncoTargets and Therapy
Matteo Giulietti, Matteo Santoni, Alessia Cimadamore, Francesco Carrozza, Francesco Piva, Liang Cheng, Antonio Lopez-Beltran, Marina Scarpelli, Nicola Battelli, Rodolfo Montironi
Tumor microenvironment constitutes a complex network in which tumor cells communicate among them and with stromal and immune cells. It has been shown that cancer cells are able to exchange genetic materials through small extracellular vesicles (EVs), a heterogeneous group of vesicles with different size and shape, cargo content, and function. The importance to investigate populations of circulating EVs would be of great importance as prostate cancer (PCa) biomarkers. In several neoplasms as well as in PCa, nanometer-sized EVs of endosomal origin are implicated in supporting tumor growth and metastatic spread by both altering local stroma cells and creating a protumor environment that favors the formation of pre-metastatic niches...
2018: Frontiers in Oncology
Pasquale Rescigno, David Lorente, David Dolling, Roberta Ferraldeschi, Daniel Nava Rodrigues, Ruth Riisnaes, Susana Miranda, Diletta Bianchini, Zafeiris Zafeiriou, Spyridon Sideris, Ana Ferreira, Ines Figueiredo, Semini Sumanasuriya, Joaquin Mateo, Raquel Perez-Lopez, Adam Sharp, Nina Tunariu, Johann S de Bono
Background: Loss of PTEN is a common genomic aberration in castration-resistant prostate cancer (CRPC) and is frequently concurrent with ERG rearrangements, causing resistance to next-generation hormonal treatment (NGHT) including abiraterone. The relationship between PTEN loss and docetaxel sensitivity remains uncertain. Objective: To study the antitumor activity of docetaxel in metastatic CRPC in relation to PTEN and ERG aberrations. Design setting and participants: Single-centre, retrospective analysis of PTEN loss and ERG expression using a previously described immunohistochemistry (IHC) binary classification system...
May 2018: European urology oncology
Pedro Barata, Hamid Emamekhoo, Prateek Mendiratta, Vadim Koshkin, Allison Tyler, Moshe Ornstein, Brian I Rini, Timothy Gilligan, Christos Kyriakopoulos, Jorge A Garcia
BACKGROUND: Androgen deprivation therapy plus docetaxel (D-ADT) increases overall survival (OS) in men with high-volume, metastatic hormone-sensitive prostate cancer (mHSPC). Although the vast majority of men initially respond to D-ADT, most will progress and develop castration-resistant prostate cancer (CRPC). Little is known about the optimal treatment sequence for men with progressive disease on D-ADT. PATIENT AND METHODS: Retrospective analysis of consecutive mHSPC patients treated with ≥3 cycles of D-ADT at Cleveland Clinic and University of Wisconsin-Madison was undertaken...
September 2018: Prostate
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