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Molecular Subgroup of Primary Prostate Cancer Presenting with Metastatic Biology.

Authors :
Walker SM
Knight LA
McCavigan AM
Logan GE
Berge V
Sherif A
Pandha H
Warren AY
Davidson C
Uprichard A
Blayney JK
Price B
Jellema GL
Steele CJ
Svindland A
McDade SS
Eden CG
Foster C
Mills IG
Neal DE
Mason MD
Kay EW
Waugh DJ
Harkin DP
Watson RW
Clarke NW
Kennedy RD
Source :
European urology [Eur Urol] 2017 Oct; Vol. 72 (4), pp. 509-518. Date of Electronic Publication: 2017 Apr 10.
Publication Year :
2017

Abstract

Background: Approximately 4-25% of patients with early prostate cancer develop disease recurrence following radical prostatectomy.<br />Objective: To identify a molecular subgroup of prostate cancers with metastatic potential at presentation resulting in a high risk of recurrence following radical prostatectomy.<br />Design, Setting, and Participants: Unsupervised hierarchical clustering was performed using gene expression data from 70 primary resections, 31 metastatic lymph nodes, and 25 normal prostate samples. Independent assay validation was performed using 322 radical prostatectomy samples from four sites with a mean follow-up of 50.3 months.<br />Outcome Measurements and Statistical Analysis: Molecular subgroups were identified using unsupervised hierarchical clustering. A partial least squares approach was used to generate a gene expression assay. Relationships with outcome (time to biochemical and metastatic recurrence) were analysed using multivariable Cox regression and log-rank analysis.<br />Results and Limitations: A molecular subgroup of primary prostate cancer with biology similar to metastatic disease was identified. A 70-transcript signature (metastatic assay) was developed and independently validated in the radical prostatectomy samples. Metastatic assay positive patients had increased risk of biochemical recurrence (multivariable hazard ratio [HR] 1.62 [1.13-2.33]; p=0.0092) and metastatic recurrence (multivariable HR=3.20 [1.76-5.80]; p=0.0001). A combined model with Cancer of the Prostate Risk Assessment post surgical (CAPRA-S) identified patients at an increased risk of biochemical and metastatic recurrence superior to either model alone (HR=2.67 [1.90-3.75]; p<0.0001 and HR=7.53 [4.13-13.73]; p<0.0001, respectively). The retrospective nature of the study is acknowledged as a potential limitation.<br />Conclusions: The metastatic assay may identify a molecular subgroup of primary prostate cancers with metastatic potential.<br />Patient Summary: The metastatic assay may improve the ability to detect patients at risk of metastatic recurrence following radical prostatectomy. The impact of adjuvant therapies should be assessed in this higher-risk population.<br /> (Copyright © 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Details

Language :
English
ISSN :
1873-7560
Volume :
72
Issue :
4
Database :
MEDLINE
Journal :
European urology
Publication Type :
Academic Journal
Accession number :
28408174
Full Text :
https://doi.org/10.1016/j.eururo.2017.03.027