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intermediate risk prostate cancer genomic

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https://www.readbyqxmd.com/read/29127096/retention-of-interstitial-genes-between-tmprss2-and-erg-is-associated-with-low-risk-prostate-cancer
#1
Stephen J Murphy, Farhad Kosari, R Jeffrey Karnes, Aqsa Nasir, Sarah H Johnson, Athanasios G Gaitatzes, James B Smadbeck, Laureano J Rangel, George Vasmatzis, John C Cheville
TMPRSS2-ERG gene fusions occur in over 50% of prostate cancers, but their impact on clinical outcomes is not well understood. Retention of interstitial genes between TMPRSS2 and ERG has been reported to influence tumor progression in an animal model. In this study, we analyzed the status of TMPRSS2-ERG fusion genes and interstitial genes in tumors from a large cohort of men treated surgically for prostate cancer, associating alterations with biochemical progression. Through whole-genome mate pair sequencing, we mapped and classified rearrangements driving ETS family gene fusions in 133 cases of very low-, low-, intermediate-, and high-risk prostate cancer from radical prostatectomy specimens...
November 10, 2017: Cancer Research
https://www.readbyqxmd.com/read/29102647/the-transcriptional-landscape-of-radiation-treated-human-prostate-cancer-analysis-of-a-prospective-tissue-cohort
#2
Simon P Keam, Franco Caramia, Cristina Gamell, Piotr J Paul, Gisela Mir Arnau, Paul J Neeson, Scott G Williams, Ygal Haupt
PURPOSE: The resistance of prostate cancer to radiation therapy (RT) is a significant clinical issue and still largely unable to be guided by patient-specific molecular characteristics. The present study describes the gene expression changes induced in response to RT in human prostate tissue obtained from a prospective tissue acquisition study designed for radiobiology research. METHODS AND MATERIALS: A prospective cohort of 5 men with intermediate-risk and clinically localized tumors were treated with high-dose-rate brachytherapy with 2 × 10-Gy fractions...
September 25, 2017: International Journal of Radiation Oncology, Biology, Physics
https://www.readbyqxmd.com/read/29045551/validation-of-a-metastatic-assay-using-biopsies-to-improve-risk-stratification-in-patients-with-prostate-cancer-treated-with-radical-radiation-therapy
#3
S Jain, C A Lyons, S M Walker, S McQuaid, S Hynes, D Mitchell, B Pang, G E Logan, A M McCavigan, D O'Rourke, D McArt, S McDade, I Mills, K M Prise, L A Knight, C J Steele, P W Medlow, V Berge, B Katz, D A Loblaw, D P Harkin, J James, J M O'Sullivan, R D Kennedy, D J Waugh
BackgroundRadiotherapy is an effective treatment for intermediate/high-risk locally-advanced prostate cancer, however, >30% of patients relapse within five years. Clinicopathological parameters currently fail to identify patients prone to systemic relapse and those whom treatment intensification may be beneficial. The purpose of this study was to independently validate the performance of a 70-gene Metastatic Assay in a cohort of diagnostic biopsies from patients treated with radical radiotherapy and androgen deprivation therapy (ADT)...
October 10, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29016610/association-between-a-17-gene-genomic-prostate-score-and-multi-parametric-prostate-mri-in-men-with-low-and-intermediate-risk-prostate-cancer-pca
#4
Michael S Leapman, Antonio C Westphalen, Niloufar Ameli, H Jeffrey Lawrence, Phillip G Febbo, Matthew R Cooperberg, Peter R Carroll
BACKGROUND: We aimed to directly compare results from multi-parametric prostate MRI (mpMRI) and a biopsy-based 17-gene RT-PCR assay providing a Genomic Prostate Score (GPS) among individuals who were candidates for active surveillance with low and intermediate risk prostate cancer (PCa). PATIENTS AND METHODS: We evaluated the association between GPS results (scale 0-100) and endorectal mpMRI findings in men with clinically localized PCa. MR studies were reviewed to a five-tier scale of increasing suspicion of malignancy...
2017: PloS One
https://www.readbyqxmd.com/read/28988753/a-biopsy-based-17-gene-genomic-prostate-score-as-a-predictor-of-metastases-and-prostate-cancer-death-in-surgically-treated-men-with-clinically-localized-disease
#5
Stephen K Van Den Eeden, Ruixiao Lu, Nan Zhang, Charles P Quesenberry, Jun Shan, Jeong S Han, Athanasios C Tsiatis, Amethyst D Leimpeter, H Jeffrey Lawrence, Phillip G Febbo, Joseph C Presti
BACKGROUND: A 17-gene biopsy-based reverse transcription polymerase chain reaction assay, which provides a Genomic Prostate Score (GPS-scale 0-100), has been validated as an independent predictor of adverse pathology and biochemical recurrence after radical prostatectomy (RP) in men with low- and intermediate-risk prostate cancer (PCa). OBJECTIVE: To evaluate GPS as a predictor of PCa metastasis and PCa-specific death (PCD) in a large cohort of men with localized PCa and long-term follow-up...
October 5, 2017: European Urology
https://www.readbyqxmd.com/read/28954787/mutational-analysis-of-gene-fusions-predicts-novel-mhc-class-i-restricted-t-cell-epitopes-immune-signatures-in-a-subset-of-prostate-cancer
#6
Jennifer L Kalina, David S Neilson, Yen-Yi Lin, Phineas T Hamilton, Alexandra Paige Comber, Emma M H Loy, S Cenk Sahinalp, Colin C Collins, Faraz Hach, Julian J Lum
PURPOSE: Gene fusions are frequently found in prostate cancer and may result in the formation of unique chimeric amino acid sequences (CASQs) that span the breakpoint of two fused gene products. This study evaluated the potential for fusion-derived CASQs to be a source of tumor neoepitopes, and determined their relationship to patterns of immune signatures in prostate cancer patients Experimental Design: A computational strategy was used to identify CASQs and their corresponding predicted MHC class I epitopes using RNA-Seq data from The Cancer Genome Atlas of prostate tumors...
September 27, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28941923/validation-of-gemcap-as-a-dna-based-biomarker-to-predict-prostate-cancer-recurrence-after-radical-prostatectomy
#7
Hao G Nguyen, Christopher Welty, Karla Lindquist, Vy Ngo, Elizabeth Gilbert, Henrik Bengtsson, Cristina Magi-Galluzzi, Jerome Jean-Gilles, Jorge Yao, Matthew Cooperberg, Edward Messing, Eric A Klein, Peter R Carroll, Pamela L Paris
PURPOSE: We aim to validate the Genomic Evaluators of Metastatic Cancer of the Prostate (GEMCaP) as a novel copy number signature predictive for prostate cancer recurrence. MATERIALS AND METHODS: We randomly selected patients who had radical prostatectomy at the Cleveland Clinic (CC) or the University of Rochester (UR) from 2000-2005. DNA isolated from the cancer region was extracted and subjected to high resolution array comparative genomic hybridization (aCGH)...
September 20, 2017: Journal of Urology
https://www.readbyqxmd.com/read/28941920/genomic-scores-are-independent-of-disease-volume-in-men-with-favorable-risk-prostate-cancer-implications-for-choosing-men-for-active-surveillance
#8
Yaw A Nyame, Dominic C Grimberg, Daniel J Greene, Karishma Gupta, Ganesh K Kartha, Ryan Berglund, Michael Gong, Andrew J Stephenson, Cristina Magi-Galluzzi, Eric A Klein
PURPOSE: We sought to determine whether disease volume at prostate biopsy would correlate with genomic scores among men with favorable risk prostate cancer. MATERIALS AND METHODS: We identified all men with NCCN® (National Comprehensive Cancer Network®) very low and low risk disease who underwent Oncotype DX® prostate testing at our institution from 2013 to 2016. Disease volume was characterized as the percent of positive cores, the number of cores with greater than 50% involvement, the largest involvement of any single core and prostate specific antigen density...
September 20, 2017: Journal of Urology
https://www.readbyqxmd.com/read/28888753/the-role-of-gut-microbiome-in-the-pathogenesis-of-prostate-cancer-a-prospective-pilot-study
#9
David M Golombos, Abimbola Ayangbesan, Padraic O'Malley, Patrick Lewicki, LaMont Barlow, Christopher E Barbieri, Chrystal Chan, Casey DuLong, Galeb Abu-Ali, Curtis Huttenhower, Douglas S Scherr
OBJECTIVE: To elucidate potential biomarkers or mechanistic principles involved with the gut microbiota and its impact on prostate cancer pathogenesis. MATERIALS AND METHODS: We performed a prospective case-control pilot study evaluating the gut microbiome of 20 men with either benign prostatic conditions (n = 8) or intermediate or high risk clinically localized prostate cancer (Gleason ≥4 + 3 cN0M0) (n = 12) undergoing care at tertiary referral center from September 1, 2015 to March 1, 2016...
September 6, 2017: Urology
https://www.readbyqxmd.com/read/28825922/risk-stratification-in-oligometastatic-prostate-cancer-where-are-we-and-what-do-we-need
#10
Alicia K Morgans, Maha Hussain
PURPOSE OF REVIEW: The oligometastatic disease state was initially described over 20 years ago as an 'intermediate' stage in metastatic cancer progression potentially amenable to curative treatment. Interest in identifying men with oligometastatic disease that may be cured has been increasing. However, whether there truly is a distinct oligometastatic state requires prospective validation, and a risk stratification system based on clinical and genomic factors is needed. RECENT FINDINGS: We reviewed the existing literature, including 11 ongoing prospective clinical trials, defining the oligometastatic state...
November 2017: Current Opinion in Urology
https://www.readbyqxmd.com/read/28753811/risk-of-upgrading-and-upstaging-among-10-000-patients-with-gleason-3-4-favorable-intermediate-risk-prostate-cancer
#11
David D Yang, Brandon A Mahal, Vinayak Muralidhar, Michelle D Nezolosky, Marie E Vastola, Shelby A Labe, Ninjin Boldbaatar, Martin T King, Neil E Martin, Peter F Orio, Clair J Beard, Karen E Hoffman, Quoc-Dien Trinh, Daniel E Spratt, Felix Y Feng, Paul L Nguyen
BACKGROUND: It is unknown whether active surveillance can be safely offered to patients with Gleason 3+4 favorable intermediate-risk (FIR) prostate cancer. OBJECTIVE: To examine the incidence and predictors of upgrading and upstaging among patients with Gleason 3+4 FIR disease. DESIGN, SETTING, AND PARTICIPANTS: The study involved 10 089 patients in the National Cancer Database diagnosed from 2010 to 2012 with Gleason 3+4 disease, prostate-specific antigen (PSA) <10ng/ml, and cT1c-2a prostate cancer with <50% positive biopsy cores (PBCs) who underwent radical prostatectomy...
June 17, 2017: European Urology Focus
https://www.readbyqxmd.com/read/28572867/prolaris-cell-cycle-progression-test-for-localized-prostate-cancer-a-health-technology-assessment
#12
(no author information available yet)
BACKGROUND: Prostate cancer is very common and many localized tumours are non-aggressive. Determining which cancers are aggressive is important for choosing the most appropriate treatment (e.g., surgery, radiation, active surveillance). Current clinical risk stratification is reliable in forecasting the prognosis of groups of men with similar clinical and pathologic characteristics, but there is residual uncertainty at the individual level. The Prolaris cell cycle progression (CCP) test, a genomic test that estimates how fast tumour cells are proliferating, could potentially be used to improve the accuracy of individual risk assessment...
2017: Ontario Health Technology Assessment Series
https://www.readbyqxmd.com/read/28528811/ability-of-a-genomic-classifier-to-predict-metastasis-and-prostate-cancer-specific-mortality-after-radiation-or-surgery-based-on-needle-biopsy-specimens
#13
Paul L Nguyen, Zaid Haddad, Ashley E Ross, Neil E Martin, Samineh Deheshi, Lucia L C Lam, Jijumon Chelliserry, Jeffrey J Tosoian, Tamara L Lotan, Daniel E Spratt, Radka S Stoyanova, Sanoj Punnen, Kaye Ong, Christine Buerki, Maria Aranes, Tyler Kolisnik, Jennifer Margrave, Kasra Yousefi, Voleak Choeurng, Elai Davicioni, Bruce J Trock, Christopher J Kane, Alan Pollack, John W Davis, Felix Y Feng, Eric A Klein
BACKGROUND: Decipher is a validated genomic classifier developed to determine the biological potential for metastasis after radical prostatectomy (RP). OBJECTIVE: To evaluate the ability of biopsy Decipher to predict metastasis and Prostate cancer-specific mortality (PCSM) in primarily intermediate- to high-risk patients treated with RP or radiation therapy (RT). DESIGN, SETTING, AND PARTICIPANTS: Two hundred and thirty-five patients treated with either RP (n=105) or RT±androgen deprivation therapy (n=130) with available genomic expression profiles generated from diagnostic biopsy specimens from seven tertiary referral centers...
November 2017: European Urology
https://www.readbyqxmd.com/read/28400167/validation-of-a-genomic-risk-classifier-to-predict-prostate-cancer-specific-mortality-in-men-with-adverse-pathologic-features
#14
R Jeffrey Karnes, Voleak Choeurng, Ashley E Ross, Edward M Schaeffer, Eric A Klein, Stephen J Freedland, Nicholas Erho, Kasra Yousefi, Mandeep Takhar, Elai Davicioni, Matthew R Cooperberg, Bruce J Trock
BACKGROUND: Risk of prostate cancer-specific mortality (PCSM) is highly variable for men with adverse pathologic features at radical prostatectomy (RP); a majority will die of other causes. Accurately stratifying PCSM risk can improve therapy decisions. OBJECTIVE: Validate the 22 gene Decipher genomic classifier (GC) to predict PCSM in men with adverse pathologic features after RP. DESIGN, SETTING, AND PARTICIPANTS: Men with adverse pathologic features: pT3, pN1, positive margins, or Gleason score >7 who underwent RP in 1987-2010 at Johns Hopkins, Cleveland Clinic, Mayo Clinic, and Durham Veteran's Affairs Hospital...
April 8, 2017: European Urology
https://www.readbyqxmd.com/read/28376608/decision-making-tools-in-prostate-cancer-from-risk-grouping-to-nomograms
#15
Paolo Fontanella, Luigi Benecchi, Angelica Grasso, Vipul Patel, David Albala, Claude Abbou, Francesco Porpiglia, Marco Sandri, Bernardo Rocco, Giampaolo Bianchi
INTRODUCTION: Prostate cancer (PCa) is the most common solid neoplasm and the second leading cause of cancer death in men. After the Partin tables were developed, a number of predictive and prognostic tools became available for risk stratification. These tools have allowed the urologist to better characterize this disease and lead to more confident treatment decisions for patients. The purpose of this study is to critically review the decision-making tools currently available to the Urologist, from the moment when PCa is first diagnosed until patients experience metastatic progression and death...
March 30, 2017: Minerva Urologica e Nefrologica, the Italian Journal of Urology and Nephrology
https://www.readbyqxmd.com/read/28358655/individual-patient-level-meta-analysis-of-the-performance-of-the-decipher-genomic-classifier-in-high-risk-men-after-prostatectomy-to-predict-development-of-metastatic-disease
#16
REVIEW
Daniel E Spratt, Kasra Yousefi, Samineh Deheshi, Ashley E Ross, Robert B Den, Edward M Schaeffer, Bruce J Trock, Jingbin Zhang, Andrew G Glass, Adam P Dicker, Firas Abdollah, Shuang G Zhao, Lucia L C Lam, Marguerite du Plessis, Voleak Choeurng, Zaid Haddad, Christine Buerki, Elai Davicioni, Sheila Weinmann, Stephen J Freedland, Eric A Klein, R Jeffrey Karnes, Felix Y Feng
Purpose To perform the first meta-analysis of the performance of the genomic classifier test, Decipher, in men with prostate cancer postprostatectomy. Methods MEDLINE, EMBASE, and the Decipher genomic resource information database were searched for published reports between 2011 and 2016 of men treated by prostatectomy that assessed the benefit of the Decipher test. Multivariable Cox proportional hazards models fit to individual patient data were performed; meta-analyses were conducted by pooling the study-specific hazard ratios (HRs) using random-effects modeling...
June 20, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28330676/stromal-gene-expression-is-predictive-for-metastatic-primary-prostate-cancer
#17
Fan Mo, Dong Lin, Mandeep Takhar, Varune Rohan Ramnarine, Xin Dong, Robert H Bell, Stanislav V Volik, Kendric Wang, Hui Xue, Yuwei Wang, Anne Haegert, Shawn Anderson, Sonal Brahmbhatt, Nicholas Erho, Xinya Wang, Peter W Gout, James Morris, R Jeffrey Karnes, Robert B Den, Eric A Klein, Edward M Schaeffer, Ashley Ross, Shancheng Ren, S Cenk Sahinalp, Yingrui Li, Xun Xu, Jun Wang, Jian Wang, Martin E Gleave, Elai Davicioni, Yinghao Sun, Yuzhuo Wang, Colin C Collins
BACKGROUND: Clinical grading systems using clinical features alongside nomograms lack precision in guiding treatment decisions in prostate cancer (PCa). There is a critical need for identification of biomarkers that can more accurately stratify patients with primary PCa. OBJECTIVE: To identify a robust prognostic signature to better distinguish indolent from aggressive prostate cancer (PCa). DESIGN, SETTING, AND PARTICIPANTS: To develop the signature, whole-genome and whole-transcriptome sequencing was conducted on five PCa patient-derived xenograft (PDX) models collected from independent foci of a single primary tumor and exhibiting variable metastatic phenotypes...
March 19, 2017: European Urology
https://www.readbyqxmd.com/read/28202223/filtration-based-enrichment-of-circulating-tumor-cells-from-all-prostate-cancer-risk-groups
#18
Julius Adebayo Awe, Jeff Saranchuk, Darrel Drachenberg, Sabine Mai
OBJECTIVE: To combine circulating tumor cell (CTC) isolation by filtration and immunohistochemistry to investigate the presence of CTCs in low, intermediate, and high-risk prostate cancer (PCa). CTCs isolated from these risk groups stained positive for both cytokeratin and androgen receptors, but negative for CD45. PATIENTS AND METHODS: Blood samples from 41 biopsy confirmed patients with PCa at different clinical stages such as low, intermediate, and high risk were analyzed...
May 2017: Urologic Oncology
https://www.readbyqxmd.com/read/28148485/prostate-cancer-recurrence-genomic-clues
#19
(no author information available yet)
In the largest genomic analysis of intermediate-risk prostate cancer samples to date, researchers have uncovered a five-element molecular signature that could help pinpoint patients whose disease is likely to recur and metastasize even after surgery or radiotherapy. They hope to develop a prognostic assay from this signature that can be used in the clinic.
February 1, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28117383/utilization-of-biopsy-based-genomic-classifier-to-predict-distant-metastasis-after-definitive-radiation-and-short-course-adt-for-intermediate-and-high-risk-prostate-cancer
#20
P L Nguyen, N E Martin, V Choeurng, B Palmer-Aronsten, T Kolisnik, C J Beard, P F Orio, M D Nezolosky, Y-W Chen, H Shin, E Davicioni, F Y Feng
BACKGROUND: We examined the ability of a biopsy-based 22-marker genomic classifier (GC) to predict for distant metastases after radiation and a median of 6 months of androgen deprivation therapy (ADT). METHODS: We studied 100 patients with intermediate-risk (55%) and high-risk (45%) prostate cancer who received definitive radiation plus a median of 6 months of ADT (range 3-39 months) from 2001-2013 at a single center and had available biopsy tissue. Six to ten 4 micron sections of the needle biopsy core with the highest Gleason score and percentage of tumor involvement were macrodissected for RNA extraction...
June 2017: Prostate Cancer and Prostatic Diseases
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