Genomic Predictors of Outcome in Prostate Cancer.
BACKGROUND
Given the highly variable behavior and clinical course of prostate cancer (PCa) and the multiple available treatment options, a personalized approach to oncologic risk stratification is important. Novel genetic approaches offer additional information to improve clinical decision making.


OBJECTIVE
To review the use of genomic biomarkers in the prognostication of PCa outcome and prediction of therapeutic response.


METHODS
Systematic literature review focused on human clinical studies reporting outcome measures with external validation. The literature search included all Medline, Embase, and Scopus articles from inception through July 2014.


RESULTS
An improved understanding of the genetic basis of prostate carcinogenesis has produced an increasing number of potential prognostic and predictive tools, such as transmembrane protease, serine2:v-ets avian erythroblastosis virus E26 oncogene homolog (TMPRSS2:ERG) gene fusion status, loss of the phosphatase and tensin homolog (PTEN) gene, and gene expression signatures utilizing messenger RNA from tumor tissue. Several commercially available gene panels with external validation are now available, although most have yet to be widely used. The most studied commercially available gene panels, Prolaris, Oncotype DX Genomic Prostate Score, and Decipher, may be used to estimate disease outcome in addition to clinical parameters or clinical nomograms. ConfirmMDx is an epigenetic test used to predict the results of repeat prostate biopsy after an initial negative biopsy. Additional future strategies include using genetic information from circulating tumor cells in the peripheral blood to guide treatment decisions at the initial diagnosis and at subsequent decision points.


CONCLUSIONS
Major advances have been made in our understanding of PCa biology in recent years. Our field is currently exploring the early stages of a personalized approach to augment traditional clinical decision making using commercially available genomic tools. A more comprehensive appreciation of value, limitations, and cost is important.


RESULTS
We summarized current advances in genomic testing in prostate cancer with a special focus on the estimation of disease outcome. Several commercial tests are currently available, but further understanding is needed to appreciate the potential benefits and limitations of these novel tests.
Department of Urology, Turku University Hospital, Turku, Finland. Electronic address: peter.j.bostrom@gmail.com.
Peter J
PJ
Boström
Department of Urology, Skåne University Hospital Malmö, Lund University, Lund Sweden.
Anders S
AS
Bjartell
Academic Urology Unit, University of Sheffield, Sheffield, UK.
James W F
JW
Catto
Section of Urology, University of Chicago, Chicago, IL, USA.
Scott E
SE
Eggener
Departments of Laboratory Medicine, Surgery (Urology), and Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK; Institute of Biomedical Technology, University of Tampere, Tampere, Finland.
Hans
H
Lilja
Department of Urology and Population Health, New York University and Manhattan Veterans Affairs Medical Center, New York, NY, USA.
Stacy
S
Loeb
Department of Urology, Radboud University Medical Center, Nijmegen, the Netherlands.
Jack
J
Schalken
Martini-Clinic, Prostate Cancer Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Thorsten
T
Schlomm
Departments of Urology and Epidemiology and Biostatistics, UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, USA.
Matthew R
MR
Cooperberg
D023281:Genomics; D006801:Humans; D008297:Male; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000628:therapy; D016896:Treatment Outcome
Cell cycle; DNA; Expression panel; Gene panel; Genetic test; Outcome; Predictive; Prognostic; Prostate cancer; RNA