EURURO Vol. 72 No. 4

509 656

Platinum Priority – Prostate Cancer
Editorial by Farhad Kosari and R. Jeffrey Karnes on pp. 519–520 of this issue
Molecular Subgroup of Primary Prostate Cancer Presenting with
Metastatic Biology
Steven M. Walker [8_TD$DIFF] Laura A. Knight [17_TD$DIFF] Andrena M. McCavigan Gemma E. Logan
Viktor Berge Amir Sherif Hardev Pandha Anne Y. Warren Catherine Davidson
Adam Uprichard Jaine K. Blayney Bethanie Price Gera L. Jellema Christopher J. Steele [18_TD$DIFF]
Aud Svindland [19_TD$DIFF] Simon S. McDade Christopher G. Eden [20_TD$DIFF] Chris Foster [21_TD$DIFF] Ian G. Mills [22_TD$DIFF]
David E. Neal [23_TD$DIFF], Malcolm D. Mason [24_TD$DIFF] Elaine W. Kay David J. Waugh D. Paul Harkin
R. William Watson [25_TD$DIFF] Noel W. Clarke [26_TD$DIFF] Richard [27_TD$DIFF]D. Kennedy
a Centre for Cancer Research and Cell Biology, Queen’s University Belfast, Belfast, UK; b Almac Diagnostics, Craigavon, UK; c Department of Pathology, RCSI,
Beaumont Hospital, Dublin, Ireland; dDepartment of Urology, Oslo University Hospital [3_TD$DIFF], Oslo, Norway; e Department of Surgical and Perioperative Sciences,
Urology and Andrology, [28_TD$DIFF]Umea University, [28_TD$DIFF]Umea, Sweden; f Department of Microbial Sciences, University of Surrey, Guildford, UK; g Department of Pathology,
Addenbrooke’s Hospital, Cambridge, UK; h
[29_TD$DIFF]Department of Pathology, Oslo University Hospital, Oslo, Norway; i Department of Urology, Royal Surrey County
Hospital, Guildford, UK; j Institute of Translational Medicine, University of Liverpool, Merseyside, UK; [30_TD$DIFF]k Department of Molecular Oncology, Oslo University
Hospital/Institute for Cancer Research, Oslo, Norway; [31_TD$DIFF]l Prostate Cancer Research Group, Centre for Molecular Medicine Norway (NCMM), University of Oslo
and Oslo University Hospitals, Forskningsparken, Oslo, Norway; [23_TD$DIFF]m Uro-oncology Research Group, Cambridge Research Institute, Cambridge, UK; [24_TD$DIFF]nWales
Cancer Bank, Cardiff University[32_TD$DIFF], School of Medicine, Health Park, Cardiff, UK; [25_TD$DIFF]oUCD School of Medicine,[4_TD$DIFF] Conway Institute, University College Dublin, Belfield,
Dublin, Ireland; [26_TD$DIFF]pChristie NHS Foundation Trust, Manchester, UK
ava ilable at
journal homepage:
Article info
Article history:
Accepted March 17, 2017
Associate Editor:
James Catto
Keywords:
Prostate cancer
Prognostic
Recurrence
Progression
Metastatic assay
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 poten-
tial at presentation resulting in a high risk of recurrence following radical prostatectomy.
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 validationwas performed using 322 rad-
ical prostatectomy samples from four sites with a mean follow-up of 50.3 [34_TD$DIFF]months.
Outcome measurements and statistical analysis: Molecular subgroups were identified
using unsupervised hierarchical clustering. A partial least squares approach was used to
generate a gene expression assay. Relationships with outcome (time to biochemical and
metastatic recurrence) were analysed using multivariable Cox regression and log-rank
analysis.
Results and limitations: A molecular subgroup of primary prostate cancer with biology
similar to metastatic disease was identified. A 70-transcript signature (metastatic assay)
was developed and independently validated in the radical prostatectomy samples.
Metastatic assay[35_TD$DIFF] positive patients had increased risk of biochemical recurrence (multi-
variable 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 [36_TD$DIFF]post surgical (CAPRA-S) identified patients at an increased
* Corresponding author. Centre for Cancer Research and Cell Biology, Queen’s University of Belfast,
97 Lisburn Road, Belfast, BT9 7BL, UK.
E-mail address: (R.D. Kennedy).
0302-2838/# 2017 European Association of Urology. Published by Elsevier B.V. This is an open access article under the CC
BY-NC-ND license ).