EURURO Vol. 71 No. 4

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of a new generation of adjuvant immune checkpoint inhibitor
trials in renal cancer .
Conflict of interest: The authors have nothing to disclose.
References
[1]
[2]
.
[3]
[4]
[5]
Teele Kuusk, Axel Bex*
Department of Urology, Division of Surgical Oncology, The Netherlands
Cancer Institute, Amsterdam, The Netherlands
*Corresponding author. Department of Urology, Division of Surgical
Oncology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066CX
Amsterdam, The Netherlands.
E-mail address: (A. Bex).
# 2017 European Association of Urology.
Published by Elsevier B.V. All rights reserved.
Re: Inherited DNA-repair Gene Mutations in Men with
Metastatic Prostate Cancer
Prichard CC, Mateo J, Walsh MF, et al
N Engl J Med 2016;375:443–53
Experts’ summary:
Cumulative data underscore the role of hereditary predispo-
sition in prostate cancer onset and progression. However,
lower frequencies of inherited mutations have posed chal-
lenges in determining their prognostic significance There-
fore, the genomic determinants of metastatic prostate cancers
remain to be further elucidated.
Genomic DNA specimens from a cohort of 692 men with
metastatic prostate cancer were analyzed for 20 DNA repair
genes known to be associated with cancer susceptibility
syndromes. A total of 84 mutations were found among
82 men with the highest frequency being BRCA2 (5.3%)
followed by ATM, CHEK2 , BRCA1, RAD51D, and
PALB2. Although these mutations were not associated with
family history or younger age, there was a significantly
higher correlation with more aggressive primary tumor
pathology (Gleason score 8–10). The evaluation of these
genes in The Cancer Genome Atlas exome sequenced data
from primary tumors showed a 4.6% frequency . Thus, the
main finding of the study of Prichard et al is the higher
rates (12%) of predisposing genetic defects in DNA repair
processes in men with metastases.
Experts’ comments:
The data provided in this study are promising and open new
opportunities by defining an earlier prognosis towards more
effective and timely treatment of patients with aggressive
prostate cancer. Due to the paucity of specimens from meta-
static prostate cancer patients, studies of this magnitude are
only feasible in a multicenter setting. These authors’ observa-
tions underscore the value of biobanks from patients
with long-term longitudinal follow-up. This type of study
provides a great example of clinical investigations along the
lines of the US Cancer Moon Shot and Precision Medicine
initiatives.
As pointed out by the authors one of the limitations of
the study was the evaluation of a selected panel of DNA
repair genes. Future investigations with a more comprehen-
sive evaluation through the whole exome or whole genome
sequencing shall further enhance these observations. Given
the race/ethnicity-associated differences of common pros-
tate cancer driver genes, for example ERG and PTEN , it will
be informative to perform analyses of DNA repair genes in
racially diverse cohorts. Based on this initiative, along with
other studies, DNA repair defect-targeted therapies
should offer new avenues for enhancing the treatment of
aggressive prostate cancer.
Conflicts of interest: The authors have nothing to disclose.
References
[1]
[2]
[3]
[4]
[5]
.
David G. McLeod*, Shiv Srivastava
Center for Prostate Disease Research, Department of Surgery, Uniformed
Services University of the Health Sciences, Bethesda, MD, USA
*Corresponding author. Center for Prostate Disease Research,
Department of Surgery, Uniformed Services University of the Health
Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814, USA.
E-mail address: (D.G. McLeod).
# 2016 Published by Elsevier B.V. on behalf of
European Association of Urology.
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