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© The Canadian Journal of Urology™; 23(2); April 2016
summarizes these criteria along with evidence or
guidelines supporting their development. Again these
referral criteria are broad in order to capture the subset
of individuals whomay benefit fromgenetic evaluation
and to enhance feasibility of referrals frombusy urologic
practices.
Genetic counseling
Patients are scheduled for genetic evaluation, which
entailsmeetingwith the genetic counselor andphysician
with expertise in cancer genetics. The genetic counselor
gathers detailed family cancer history information
regarding maternal and paternal sides of the family as
well as ancestry in order to gauge suspicion for inherited
predisposition to prostate cancer and other hereditary
cancer syndromes. The genetic counselor also discusses
basic genetics, cancer inheritance patterns, information
to be gained from genetic testing, limitations or
uncertainties from test results, additional cancer risks
for patients based on mutations in specific genes, and
implications for the patient and their family. Additional
discussion includes any insurance barriers to having
testing covered, payment plans offered by testing labs,
and genetic discrimination laws (what is covered and
not covered). The physician expands upon any area of
genetics and familial implications, discusses potential
medical management based upon test results, and open
studies for which the patient may be eligible.
Genetic testing and disclosure
At this time, clinical genetic testing not associatedwith a
clinical research study is limited to testing for mutations
in
BRCA1
and
BRCA2
as supported by current NCCN
practice guidelines (NCCN Genetic/Familial High-
Risk Assessment: Breast and Ovarian version 2.2015).
The specific NCCN genetic evaluation criteria include
personal historyof prostate cancer (Gleason≥7) at anyage
with ≥ 1 close blood relativewith breast (≤ 50 years) and/
or invasive ovarian and/or pancreatic or prostate cancer
(Gleason score ≥ 7) at any age. These criteriahighlight the
importance of obtaining a detailed and thorough family
cancer history on the maternal and paternal sides of the
family for an individual presenting for prostate cancer
risk evaluation. Occasionally, it may be recommended
that a blood relative of the prostate cancer patient is
the optimal person to test in the family. For example, if
the patient has a sister with young age at breast cancer
diagnosis, her genetic test resultmaybemore informative
regarding mutation status in the family and may have
a greater chance of insurance coverage. Once genetic
test results are available, the patient returns for a results
disclosure visit with the genetic counselor and physician
to review the test results and interpretation of findings.
8252
How I Do It: Genetic counseling and genetic testing for inherited prostate cancer
Genetically-based management
Positive for mutation
If a
BRCA1
or
BRCA2
mutation is identified in the
proband, thedisclosure session is focusedondiscussionof
the role of thatmutation inprostate cancer predisposition
and the risk for other cancers implicated in the
BRCA
-
spectrum.
5,14
These additional cancers include cancers
of the breast, ovary, pancreas, and melanoma. The
discussion is primarily focused on additional cancer
screening that may be considered by the prostate cancer
proband due to the elevated cancer risks, such as male
breast cancer screening, pancreatic cancer screening, and
skincancer screening. NCCNguidelines recommend that
male
BRCA
mutation carriers have a clinical breast exam
every 12 months starting at age 35, and be taught how to
perform their own breast exam also starting at age 35.
5
There are currently no standard guidelines for pancreatic
cancer screening, and therefore patients with
BRCA
mutations are referred to gastroenterology to discuss the
pros and cons of pancreatic cancer screening approaches.
BRCA
mutation carriers are also referred to dermatology
for focusedskinexamofmoles or suspicious skinfindings
and to continue on yearly dermatologic visits. The role
of
BRCA
mutations in prostate cancer management is
emerging. Recent datademonstrate superior response of
prostate cancer patientswithmetastatic, castrate-resistant
disease and a
BRCA
mutation to PARP inhibition.
15
Precision medicine efforts are expected to significantly
advance the translational impact of genetic data in the
management of localized and advanced prostate cancer.
Another important focus of discussion for
BRCA
mutation carriers is genetic testing for blood relatives.
Unaffectedmale relatives (sons, brothers, nephews) could
undergo site-specific genetic testing for the mutation
identified in the proband to determine if they have
inherited themutation. Forunaffectedmale relativeswith
a
BRCA
mutation identified, one issue to discuss is how
this impacts prostate cancer screening strategies. Current
NCCNguidelines recommendprostate cancer screening
starting at age 40 for
BRCA2
mutation carriers, and to
consider screening starting at age 40 for
BRCA1
mutation
carriers.
5
Additional data from the ongoing IMPACT
study (an international study investigating the role of
BRCA1
,
BRCA2
and Lynch syndrome gene alterations in
prostate cancer screeningoutcomes)may informprostate
cancer screening guidelines by mutation status.
16
Negative for mutation
For patients not found to carry a
BRCA
mutation and no
known mutation in the family, the result is interpreted
as “inconclusive” since there may be additional genetic
factors contributing to inherited prostate cancer beyond