©TheCanadian Journal ofUrology™: International Supplement, April 2014
3
GomellaETAL.
Roleof imaging inCRPC
Determining the transition of CRPC tomCRPC is of
vital importance for many reasons. First, the early
identificationofasymptomaticbonymetastatic lesions
may allow intervention to minimize the burden in
termsofmorbidityandcostofskeletal relatedevents.
11
Secondly, medications such as sipuleucel-T are only
indicated forasymptomaticorminimallysymptomatic
mCRPC.
12
Thisprogression tomCRPCwithdetectable
radiographic lesions is a seminal event significantly
affecting treatment decisions. There is currently
little formal guidance concerning the frequency
of imaging in patients without symptoms. Recent
recommendations by the RadiographicAssessments
for Detection of Advanced Recurrence (RADAR)
Group have been published in attempt to address
these limitations.
13
In addition to standard imaging
technologies, a series of newer imaging modalities
such as F-18 PET, 11 C-choline PET are becoming
available to identifymore accurately the presence of
earlymetastatic prostate cancer before routine bone
scandetection. Prostate cancer imagingadvancesare
reviewedbyDr. Leung and associates.
14
Immunotherapy inCRPC
Whileprostatecancerhastraditionallybeenconsidered
a “non-immunogenic tumor” recent discoveries have
made prostate cancer a target of immunotherapy.
15
Theactivecellular immunotherapy,sipuleucel-T,wasa
first-in-classagent approved formCRPC in2010. This
was based on the 4.1months survival in the IMPACT
trial demonstrating superiorityof thisnovel approach
in mCRPC.
16
The review by Gomella and associates
discusses the development of sipuleucel-T and other
evolving immunotherapy strategies and addresses
the practical applications of administration of the
sipuleucel-T.
12
Androgenbiosynthesis inhibition
AsnotedbyTilkiandEvans, theandrogenaxisremains
active in the setting of CRPC.
1
This observation and
others including thediscovery thatmetastaticprostate
cancer cangenerate its own androgens has led to the
development of agents that can impact androgen
production inallsites in thebody, includingwithin the
tumor itself. Abiraterone isthefirstapprovedandrogen
biosynthesis inhibitor for mCRPC. Abiraterone
acetate, apregnenolonederivative, isanoral inhibitor
of the steroidogenic enzyme CYP17. Abiraterone
possesses dual 17-
α
hydroxylase and C17,20-lyase
blockingactivity thatresults indecreasedgonadaland
extra-gonadal androgen synthesis.
17
While initially
approved for post-docetaxel administration, it is
now available in the pre-chemotherapy setting. The
development, mechanisms of action and practical
treatment considerations of abiraterone are reviewed
byMostaghel andLin.
18
Inhibitionof theandrogenreceptorsignaling
pathway
In considering the androgen sensitivity of CRPC,
inhibitionof theandrogen receptor signalingpathway
is a viable strategy. Enzalutamide, formerly known
as MDV3100, was developed and now approved as
an orally administered androgen receptor inhibitor
indicated for the treatment of patients withmCRPC
who have previously received docetaxel. In contrast
to the androgen receptor blocker bicalutamide,
enzalutamidehasnoagonistproperties. Enzalutamide
competitively inhibits androgen receptor binding
and androgen receptor nuclear translocation and
interaction with DNA.
19
Based on the results of
the recently reported PREVAIL trial (enzalutamide
in the pre-chemotherapy mCRPC setting) at the
American Society of Clinical Oncology (ASCO) 2014
Genitourinary (GU) Cancers Symposium in San
Francisco, it is widely anticipated that this agent
will be approved in this setting in the future.
20
The
PREVAILtrialdemonstrated improvedoverallsurvival
and radiographic progression-free survival in patient
withmCRPCwho have not received chemotherapy.
Drs.Hoffman-CensitsandKellyprovideanintroduction
to thepreliminaryclinical trials that support theuseof
enzalutamideanddiscuss thepractical applicationsof
enzalutamide for the clinician.
21
Bone targeted therapy with radium 223
dichloride
Ahallmarkofadvancedprostatecancer is the frequent
involvementof thebone. Thesemetastatic lesionscan
causepainor result in skeletal related events such as
spinal cord compression or fractureswith the extent
of osseousmetastasis directly correlatedwithoverall
survival. Radiopharmaceuticals have been available
for many years to palliate painful bony metastasis.
Commonlyused agents to treat prostate cancer bony
metastasis have included the beta particle emitting
agents strontium 89 and samarium 153withmarrow
suppressionbeing theirmain limiting toxicity. While
effectiveatshort termpalliation,neitherof theseagents
hasshownanyutility inextendingsurvival.
22
Radium
