Abstract
Men who inherit pathogenic germline mutations in BRCA2 and BRCA1 are at increased risk of developing aggressive prostate cancer, and those with germline
mutations in other DNA repair genes such as ATM, CHEK2, and MSH2/MSH6 may also have increased risks. Although clinically important, there is lack of specific
guidance regarding management strategies for men at increased risk owing to germline
mutation status or family history of aggressive prostate cancer. We review prostate
cancer genetic risk factors and the ongoing IMPACT (Identification of Men with a genetic
predisposition to ProstAte Cancer: Targeted screening in BRCA1/2 mutation carriers and controls) screening study. Pending results of IMPACT and unified
guidelines, there are areas of uncertainty and need for further study. Ongoing and
future research will be critical for optimizing prostate cancer screening approaches
for men at the highest risk for aggressive prostate cancer. In the interim, we propose
a practical approach to prostate cancer screening for men with a germline mutation
in a known/suspected moderate to high-penetrance cancer predisposition gene (eg, BRCA1/2), and/or men with a first- or second-degree relative with metastatic prostate cancer
(regardless of genetic testing): baseline prostate-specific antigen and digital rectal
exam by experienced providers at age 40 years or 5 years earlier than age of diagnosis
of the youngest first- or second-degree relative with metastatic prostate cancer,
whichever is earlier. Then, based on age, digital rectal exam, and prostate-specific
antigen, we suggest consideration of magnetic resonance imaging, biopsy, and/or continued
monitoring.
Keywords
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Article info
Publication history
Published online: May 31, 2017
Accepted:
May 23,
2017
Received in revised form:
May 17,
2017
Received:
April 21,
2017
Identification
Copyright
© 2017 Elsevier Inc. All rights reserved.
