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Teemu D Laajala, Mika Murtojärvi, Arho Virkki, Tero Aittokallio
Motivation: Prognostic models are widely used in clinical decision-making, such as risk stratification and tailoring treatment strategies, with the aim to improve patient outcomes while reducing overall healthcare costs. While prognostic models have been adopted into clinical use, benchmarking their performance has been difficult due to lack of open clinical datasets. The recent DREAM 9.5 Prostate Cancer Challenge carried out an extensive benchmarking of prognostic models for metastatic Castration-Resistant Prostate Cancer (mCRPC), based on multiple cohorts of open clinical trial data...
June 15, 2018: Bioinformatics
Srinivas R Viswanathan, Gavin Ha, Andreas M Hoff, Jeremiah A Wala, Jian Carrot-Zhang, Christopher W Whelan, Nicholas J Haradhvala, Samuel S Freeman, Sarah C Reed, Justin Rhoades, Paz Polak, Michelle Cipicchio, Stephanie A Wankowicz, Alicia Wong, Tushar Kamath, Zhenwei Zhang, Gregory J Gydush, Denisse Rotem, J Christopher Love, Gad Getz, Stacey Gabriel, Cheng-Zhong Zhang, Scott M Dehm, Peter S Nelson, Eliezer M Van Allen, Atish D Choudhury, Viktor A Adalsteinsson, Rameen Beroukhim, Mary-Ellen Taplin, Matthew Meyerson
Nearly all prostate cancer deaths are from metastatic castration-resistant prostate cancer (mCRPC), but there have been few whole-genome sequencing (WGS) studies of this disease state. We performed linked-read WGS on 23 mCRPC biopsy specimens and analyzed cell-free DNA sequencing data from 86 patients with mCRPC. In addition to frequent rearrangements affecting known prostate cancer genes, we observed complex rearrangements of the AR locus in most cases. Unexpectedly, these rearrangements include highly recurrent tandem duplications involving an upstream enhancer of AR in 70%-87% of cases compared with <2% of primary prostate cancers...
June 11, 2018: Cell
Yi-Mi Wu, Marcin Cieślik, Robert J Lonigro, Pankaj Vats, Melissa A Reimers, Xuhong Cao, Yu Ning, Lisha Wang, Lakshmi P Kunju, Navonil de Sarkar, Elisabeth I Heath, Jonathan Chou, Felix Y Feng, Peter S Nelson, Johann S de Bono, Weiping Zou, Bruce Montgomery, Ajjai Alva, Dan R Robinson, Arul M Chinnaiyan
Using integrative genomic analysis of 360 metastatic castration-resistant prostate cancer (mCRPC) samples, we identified a novel subtype of prostate cancer typified by biallelic loss of CDK12 that is mutually exclusive with tumors driven by DNA repair deficiency, ETS fusions, and SPOP mutations. CDK12 loss is enriched in mCRPC relative to clinically localized disease and characterized by focal tandem duplications (FTDs) that lead to increased gene fusions and marked differential gene expression. FTDs associated with CDK12 loss result in highly recurrent gains at loci of genes involved in the cell cycle and DNA replication...
June 14, 2018: Cell
Giuseppe De Vincentis, Fabio Monari, Sergio Baldari, Matteo Salgarello, Viviana Frantellizzi, Elisabetta Salvi, Luigi Reale, Silvia Napolitano, Giario Conti, Enrico Cortesi
AIM: To describe the journey of patients with metastatic castration-resistant prostate cancer (mCRPC) in treatment with radium-223. METHODS: A multiperspective analysis was performed using narrative medicine in four Italian centers. RESULTS: The substantial impact of mCRPC on quality of life through all phases of the disease was described. After an initial lack of awareness of the disease or denial of its effects, symptoms of pain, fatigue and side effects often led to sadness, fear and loneliness...
June 15, 2018: Future Oncology
Andika Afriansyah, Agus Rizal Ardy Hariandy Hamid, Chaidir Arif Mochtar, Rainy Umbas
Aim: Metastatic prostate cancer (mPCa) has a poor outcome with median survival of two to five years. The use of androgen deprivation therapy (ADT) is a gold standard in management of this stage.  Aim of this study is to analyze the prognostic value of PSA kinetics of patient treated with hormonal therapy related to survival from several published studies Method: Systematic review and meta-analysis was performed using literature searching in the electronic databases of MEDLINE, Science Direct, and Cochrane Library...
2018: F1000Research
Pedro Barata, Hamid Emamekhoo, Prateek Mendiratta, Vadim Koshkin, Allison Tyler, Moshe Ornstein, Brian I Rini, Timothy Gilligan, Christos Kyriakopoulos, Jorge A Gracia
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...
June 7, 2018: Prostate
Atish D Choudhury, Kathryn P Gray, Jeffrey G Supko, Lauren C Harshman, Mary-Ellen Taplin, Amanda F Pace, Matthew Farina, Katherine A Zukotynski, Brandon Bernard, Philip W Kantoff, Mark Pomerantz, Christopher Sweeney
BACKGROUND: Cabozantinib can enhance the effect of abiraterone in preclinical prostate cancer models. This study aimed to define the recommended phase 2 dose (RP2D) and preliminary efficacy of abiraterone + cabozantinib in mCRPC. METHODS: Patients with progressive mCRPC with 0-2 prior chemotherapy regimens but no prior CYP17A1 or MET inhibitor received abiraterone acetate at 1000 mg daily with prednisone 5 mg BID in combination with cabozantinib at 20, 40, or 60 mg daily in a dose-escalation 3 + 3 open-label phase 1 design (Part A)...
June 7, 2018: Prostate
Consuelo Buttigliero, Marcello Tucci, Francesca Vignani, Rosario F Di Stefano, Gianmarco Leone, Clizia Zichi, Daniele Pignataro, Gaetano Lacidogna, Pamela Guglielmini, Gianmauro Numico, Giorgio V Scagliotti, Massimo Di Maio
BACKGROUND: Neutropenia is a common side effect associated with docetaxel use. We retrospectively investigated the association between chemotherapy-induced neutropenia and survival in metastatic castration-resistant prostate cancer (mCRPC) patients receiving first-line docetaxel. PATIENTS AND METHODS: Metastatic castration-resistant prostate cancer patients treated with first-line docetaxel, with known neutrophils value 10 days after first administration, were included in this retrospective analysis...
June 1, 2018: Clinical Genitourinary Cancer
Landon C Brown, Guru Sonpavde, Andrew J Armstrong
BACKGROUND: Intermediate endpoints are needed in early phase studies of men with metastatic castration-resistant prostate cancer (mCRPC) that can reliably predict success in phase 3 trials. Among men with measurable disease, objective response may provide information as to whether a treatment is likely to be successful. METHODS: We conducted a systematic review of systemic agents that have proceeded to phase 3 trials in men with mCRPC and examined the relationship between improvements in measurable disease response in phase 2 trials and successful phase 3 trials leading to regulatory approval...
June 1, 2018: Prostate Cancer and Prostatic Diseases
Manish Kohli, Jian Li, Meijun Du, David W Hillman, Scott M Dehm, Winston Tan, Rachel Carlson, Michael B Campion, Liguo Wang, Liewei Wang, Huijuan Zhang, Peng Zhang, Deepak Kilari, Chiang-Ching Huang, Liang Wang
BACKGROUND: The prognostic significance of plasma cell-free DNA (cfDNA) androgen receptor amplification (ARamp) in metastatic castration-resistant prostate cancer (mCRPC) compared with circulating tumor cell (CTC) counts is not known. METHODS: As part of correlative aims of a prospective study in mCRPC, concurrent and serial collections of plasma and CTCs were performed. Specimen collections were performed at baseline after progression on androgen deprivation therapy and then 12 weeks later...
June 1, 2018: Prostate Cancer and Prostatic Diseases
Karthik V Giridhar, Cristobal Sanhueza, David W Hillman, Hassan Alkhateeb, Rachel Carlson, Winston Tan, Brian A Costello, Fernando Quevedo, Lance Pagliaro, Manish Kohli
OBJECTIVE: To determine the prognostic value of serum chromogranin-A (CGA) in a two-cohort study of men with metastatic castrate resistant prostate cancer (mCRPC) and to compare with circulating tumor cells (CTCs)-based prognosis. PATIENTS AND METHODS: A two-cohort-based evaluation for serum CGA for prognostication in CRPC stage was performed using a screening cohort of 256 men with mCRPC and an independent validation cohort of 92 men with mCRPC. In both cohorts, men receiving proton pump inhibitors and those with non-castrate levels of testosterone (>50 ng/dl) were excluded...
June 1, 2018: Prostate Cancer and Prostatic Diseases
Emmanuel S Antonarakis, Eric J Small, Daniel Petrylak, David I Quinn, Adam S Kibel, Nancy Chang, Erica Dearstyne, Matthew Harmon, Dwayne Campogan, Heather Haynes, Tuyen Vu, Nadeem A Sheikh, Charles G Drake
BACKGROUND: Sipuleucel-T is FDA-approved for the treatment of metastatic castration-resistant prostate cancer (mCRPC) based on the IMPACT trial showing a 4.1-month benefit in median overall survival (OS) for patients receiving sipuleucel-T vs control. Although efficacy of sipuleucel-T is well-established, its mechanism remains incompletely understood. METHODS: Patient samples from three sipuleucel-T trials were assessed for peripheral cellular immune responses to the immunogen PA2024 and the target antigen prostatic acid phosphatase (PAP)...
June 1, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
S Knipper, P Mandel, G V Amsberg, P Strölin, M Graefen, T Steuber
BACKGROUND: Multiple experimental approaches are meanwhile available for progressive metastatic castration resistant prostate cancer (mCRPC) patients after failure of guideline recommended therapy (i. e., chemotherapy and/or hormonal treatment). We evaluated the outcome of metronomic chemotherapy with cyclophosphamide (CY) in combination with low-dose prednisolone. MATERIALS AND METHODS: A total of 14 mCRPC-patients were treated with CY 50 mg/day (plus prednisolone 10 mg/day) between November 2012 and September 2017 after being resistant or unfit for chemotherapy and/or further hormonal treatment...
May 28, 2018: Der Urologe. Ausg. A
M Schostak, F König, M Bögemann, P Goebell, P Hammerer, S Machtens, C Schwentner, C Thomas, G von Amsberg, F-C von Rundstedt, A Heidenreich
In March 2017 the 'Advanced Prostate Cancer Consensus Conference' (APCCC) took place in St. Gallen (Switzerland). The APCCC-panelists are internationally well known experts. With the actual data in mind they discussed treatment options for patients with advanced prostate cancer in order to update the international APCCC-recommendations from the previous meeting in 2015. Recently these consensus recommendations have been published in "European Urology".A group of German experts discussed this year APCCC-votes during the meeting and the recommendations that were concluded from the votes from the German perspective...
May 28, 2018: Der Urologe. Ausg. A
Andrew J Armstrong, Aseem Anand, Lars Edenbrandt, Eva Bondesson, Anders Bjartell, Anders Widmark, Cora N Sternberg, Roberto Pili, Helen Tuvesson, Örjan Nordle, Michael A Carducci, Michael J Morris
Importance: Prostate cancer commonly metastasizes to bone, and bone metastases are associated with pathologic fractures, pain, and reduced survival. Bone disease is routinely visualized using the technetium Tc 99m (99mTc) bone scan; however, the standard interpretation of bone scan data relies on subjective manual assessment of counting metastatic lesion numbers. There is an unmet need for an objective and fully quantitative assessment of bone scan data. Objective: To clinically assess in a prospectively defined analysis plan of a clinical trial the automated Bone Scan Index (aBSI) as an independent prognostic determinant of overall survival (OS) in men with metastatic castration-resistant prostate cancer (mCRPC)...
May 17, 2018: JAMA Oncology
Yongquan Wang, Heng Zhang, Wenhao Shen, Peng He, Zhansong Zhou
PURPOSE: Castration-resistant prostate cancer (CRPC) refers to prostate cancer that has progressed after initial androgen deprivation therapy (ADT). Over the years, treatment strategies for metastatic CRPC (mCRPC) have undergone considerable changes. We performed a network meta-analysis to assess the effectiveness and tolerability of targeted agents for mCRPC. METHODS: We search databases including MEDLINE, EMBASE, and the Cochrane Library through Sep 5, 2017. The major effectiveness outcomes were progression-free survival (PFS) and overall survival (OS)...
May 24, 2018: Journal of Cancer Research and Clinical Oncology
Fred Saad, Frédéric Pouliot, Brita Danielson, Charles Catton, Anil Kapoor
Multiple new agents to treat metastatic castration-resistant prostate cancer (mCRPC) have become available in recent years; however, the appropriate timing and sequencing of these agents have yet to be elucidated. Until accurate biomarkers become available to allow more focused therapeutic targeting for this population, treatment selection for men with mCRPC will continue to be driven largely by close assessment of patient-related factors and symptoms. Pain, as the predominant symptom of mCRPC, is often the focus when assessing progression and the need for a change in treatment...
May 14, 2018: Canadian Urological Association Journal, Journal de L'Association des Urologues du Canada
Angelo Castello, H A Macapinlac, E Lopci, E B Santos
PURPOSE: Prostate-specific antigen (PSA) flare is a well-known phenomenon in patients with prostate cancer, but its impact during radium-223 dichloride (223 RaCl2 ) therapy is still unclear. This radioisotope has shown to improve overall survival in metastatic castration-resistant prostate cancer (mCRPC). We sought to evaluate the impact of PSA flare on survival and its relation with metabolic parameters on 18 F-labeled sodium fluoride PET/CT. METHODS: We conducted a retrospective study of 168 patients with mCRPC (median age 69; median PSA 29...
May 21, 2018: European Journal of Nuclear Medicine and Molecular Imaging
Vittore Cereda, Vincenzo Formica, Mario Roselli
There is general agreement that increased angiogenesis is an important factor in determining prostate cancer development and prognosis. Vascular Endothelial Growth Factor (VEGF) is thought to play a primary role in the molecular events that lead to prostate cancer progression, from androgen-dependency to castration-resistance until dissemination to the skeleton. Bevacizumab is a recombinant anti-VEGF monoclonal antibody that has exhibited clinical activity in different cancer types. Areas covered: In this review we summarize the data of clinical trials, investigating the effects of bevacizumab in prostate cancer patients...
May 21, 2018: Expert Opinion on Biological Therapy
Gesa Isensee, Anne Péporté, Joachim Müller, Sabine Schmid, Silke Gillessen, Aurelius Omlin
INTRODUCTION: Radium-223 is an approved survival-prolonging treatment option in men with castration-resistant prostate cancer (mCRPC) and bone metastases. In the registration trial (ALSYMPCA), no regular imaging was mandated. We aimed to analyze men with metastatic mCRPC treated with radium-223 who had bone scintigraphy for staging and treatment monitoring. PATIENTS AND METHODS: Retrospective chart review was performed of mCRPC patients who received 6 cycles of radium-223 and who underwent bone scintigraphy before start of radium-223 and after 3 and 6 cycles of treatment...
April 23, 2018: Clinical Genitourinary Cancer
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