EURURO Vol. 73 No. 1

129 148

Prostate Cancer
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
Stephen K. Van Den Eeden
Jeong S. Han
Phillip G. Febbo
a Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA; b Genomic Health Inc., Redwood City, CA, USA; c Division of Pathology,
Kaiser Oakland Medical Center, Oakland, CA, USA; dDivision of Urology, Kaiser Oakland Medical Center, Oakland, CA, USA
ava ilable at
journal homepage:
Article info
Article history:
Accepted September 2, 2017
Associate Editor:
James Catto
Keywords:
Gene expression
Molecular diagnostic testing
Prostate cancer
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Abstract
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-specifi c death (PCD)
in a large cohort of men with localized PCa and long-term follow-up.
Design, setting, and participants: A retrospective study using a stratified cohort sam-
pling design was performed in a cohort of men treated with RP within Kaiser Perma-
nente Northern California. RNA from archival diagnostic biopsies was assayed to
generate GPS results.
Outcome measurements and statistical analysis: We assessed the association between
GPS and time to metastasis and PCD in prespecified uni- and multivariable statistical
analyses, based on Cox proportional hazard models accounting for sampling weights.
Results and limitations: The final study population consisted of 279 men with low-,
intermediate-, and high-risk PCa between 1995 and 2010 (median follow-up 9.8 yr), and
included 64 PCD and 79 metastases. Valid GPS results were obtained for 259 (93%). In
univariable analysis, GPS was strongly associated with time to PCD, hazard ratio (HR)/20
GPS units = 3.23 (95% confidence interval [CI] 1.84– 5.65; p < 0.001), and time to metas-
tasis, HR/20 units = 2.75 (95% CI 1.63–4.63; p < 0.001). The association between GPS and
both end points remained significant after adjusting for National Comprehensive Cancer
Network, American Urological Association, and Cancer of the Prostate Risk Assessment
(CAPRA) risks (p < 0.001). No patient with low- or intermediate-risk disease and a GPS
of < 20 developed metastases or PCD (n = 31). In receiver operating characteristic
analysis of PCD at 10 yr, GPS improved the c-statistic from 0.78 (CAPRA alone) to
0.84 (GPS + CAPRA; p < 0.001). A limitation of the study was that patients were treated
during an era when definitive treatment was standard of care with little adoption of
active surveillance.
Conclusions: GPS is a strong independent predictor of long-term outcomes in clinically
localized PCa in men treated with RP and may improve risk stratification for men with
newly diagnosed disease.
Patient summary: Many prostate cancers are slow growing and unlikely to spread
or threaten a man ’s life, while others are more aggressive and require treatment.
* Corresponding author. Division of Research, Kaiser Permanente, 2000 Broadway, Oakland,
CA 94612, USA. Tel. +1-510-891-3718; Fax: +1-510-891-3761.
E-mail address: (S.K. Van Den Eeden).
0302-2838/© 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.