Molecular Subgroup of Primary Prostate Cancer Presenting with Metastatic Biology

Walker, SM, Knight, LA, McCavigan, AM, Logan, GE, Berge, V, Sherif, A, Pandha, Hardev, Warren, AY, Davidson, C, Uprichard, A et al, Blayney, JK, Price, B, Jellema, GL, Svindland, A, McDade, SS, Eden, CG, Foster, C, Mills, IG, Neal, DE, Mason, MD, Kay, EW, Waugh, DJ, Harkin, DP, Watson, RW, Clarke, NW and Kennedy, RD (2017) Molecular Subgroup of Primary Prostate Cancer Presenting with Metastatic Biology European Urology, 72 (4). pp. 509-518.

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Abstract

BACKGROUND: Approximately 4-25% of patients with early prostate cancer develop disease recurrence following radical prostatectomy. OBJECTIVE: To identify a molecular subgroup of prostate cancers with metastatic potential at presentation resulting in a high risk of recurrence following radical prostatectomy. DESIGN, SETTING &amp; 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. OUTCOME MEASURES &amp; 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 analyzed using multivariable Cox regression and log-rank analysis. RESULTS &amp; 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 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 CAPRA-S identified patients at 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. CONCLUSIONS: The Metastatic Assay may identify a molecular subgroup of primary prostate cancers with metastatic potential. 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.

Item Type:	Article
Subjects :	Biosciences and Medicine
Divisions :	Faculty of Health and Medical Sciences > School of Biosciences and Medicine
Authors :	Name Email ORCID Walker, SM UNSPECIFIED UNSPECIFIED Knight, LA UNSPECIFIED UNSPECIFIED McCavigan, AM UNSPECIFIED UNSPECIFIED Logan, GE UNSPECIFIED UNSPECIFIED Berge, V UNSPECIFIED UNSPECIFIED Sherif, A UNSPECIFIED UNSPECIFIED Pandha, Hardev H.Pandha@surrey.ac.uk UNSPECIFIED Warren, AY UNSPECIFIED UNSPECIFIED Davidson, C UNSPECIFIED UNSPECIFIED Uprichard, A UNSPECIFIED UNSPECIFIED Blayney, JK UNSPECIFIED UNSPECIFIED Price, B UNSPECIFIED UNSPECIFIED Jellema, GL UNSPECIFIED UNSPECIFIED Svindland, A UNSPECIFIED UNSPECIFIED McDade, SS UNSPECIFIED UNSPECIFIED Eden, CG UNSPECIFIED UNSPECIFIED Foster, C UNSPECIFIED UNSPECIFIED Mills, IG UNSPECIFIED UNSPECIFIED Neal, DE UNSPECIFIED UNSPECIFIED Mason, MD UNSPECIFIED UNSPECIFIED Kay, EW UNSPECIFIED UNSPECIFIED Waugh, DJ UNSPECIFIED UNSPECIFIED Harkin, DP UNSPECIFIED UNSPECIFIED Watson, RW UNSPECIFIED UNSPECIFIED Clarke, NW UNSPECIFIED UNSPECIFIED Kennedy, RD UNSPECIFIED UNSPECIFIED
Date :	10 April 2017
Identification Number :	10.1016/j.eururo.2017.03.027
Copyright Disclaimer :	Copyright 2017 European Association of Urology. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Uncontrolled Keywords :	prostate cancer, prognostic, recurrence, progression, Metastatic Assay
Related URLs :	Publisher
Depositing User :	Symplectic Elements
Date Deposited :	02 May 2017 17:54
Last Modified :	13 Sep 2017 13:13
URI:	http://epubs.surrey.ac.uk/id/eprint/814092

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