©TheCanadian Journal ofUrology™: International Supplement, April 2014
AddresscorrespondencetoDr.EricWinquist,LondonHealth
SciencesCentre,790CommissionersRoadEast,London,ON
N6A4L6Canada
Secondaryhormonalmanipulation in
castration resistant prostate cancer
SohaibAl-Asaaed,MD, EricWinquist,MD
LondonHealthSciencesCentre andWesternUniversity, London,Ontario, Canada
AL-ASAAEDS,WINQUISTE.Secondaryhormonal
manipulation incastrationresistantprostatecancer.
Can JUrol
2014;21(Suppl 1):37-41.
Introduction:
Castration resistant prostate cancer
(CRPC) is the single common pathway to prostate
cancer death. For men with symptomatic metastatic
disease, docetaxel chemotherapy remains a standard of
care. However, blood prostatic-specific antigen (PSA)
testing allows the identification of CRPC before clinical
metastasesorsymptomsoccur,providinga longdiagnostic
lead time in many patients. The use of secondary
hormonalmanipulations (SHMs) inmennot candidates
for immediate chemotherapy is reviewed.
Materials and methods:
PubMed was searched for
randomized clinical trials, systematic reviews or clinical
practice guidelines addressingSHMs inCRPC.
Results:
Arecentsystematicreviewandpracticeguideline
was identified,andusedastheevidencebase forthisreview
alongwithreports fromrandomizedtrialsoverthepastyear.
Conclusions:
Thegoalsof therapywithSHMsshouldbe
discussedwithpatients and their preferences considered.
Inmenwithout clinical evidence of metastases, gonadal
androgensuppressionshouldbemaintainedandgenerally
patients should be observed. There is no clear evidence
that SHMs are of benefit in these patients. Abiraterone
plus prednisone is of proven benefit inmenwithCRPC
metastases who are without significant symptoms prior
to chemotherapy. Basedon emergingdata, enzalutamide
may be of similar benefit. Use of other SHMs should
be based on patient preference and consideration of
possible adverse effects; with the exception of low dose
prednisone, there is little evidence of benefit supporting
their use. For patients accepting these uncertainties, a
trialofnonsteroidalantiandrogenmaybeconsideredasan
adjunct toobservation, followedby lowdosecorticosteroid
with immediateordelayedadditionofabiraterone (inmen
withmetastases) as a reasonable next step.
KeyWords:
enzalutamide, hormone-dependent,
prostaticneoplasms,castrationresistant,abiraterone,
drug therapy
There is no clear temporal relationship between the
onset of metastatic disease and the development of
CRPC, though biochemical recurrence characterized
byan increasingbloodprostatic-specificantigen (PSA)
level alone is usually the first evidence of CRPC.
4-6
Thus the emergence of CRPC is often characterized
by a lengthy “lead time” duringwhichmenwithout
clinical evidence of metastases are observed to have
risingPSA levels.
CRPC is aheterogeneousdiseaseand consists of a
spectrum of clinical states. When consideringuse of
secondaryhormonalmanipulations (SHMs) it isuseful
toconsiderpatients in threeclinically-definedgroups:
1) those with biochemical recurrence alone without
any evidence of metastases, 2) those with evidence
of metastatic disease andminimal or no symptoms,
Introduction
Menwith castration resistant prostate cancer (CRPC)
and clinically significant metastatic disease (rapid
disease progression, persistent and worsening
symptoms, orvisceralmetastases) shouldbeassessed
forpalliativechemotherapy,whichremainsastandard
of care,withdocetaxel currently theagentof choice.
1,2
ThediagnosisofCRPC ismadewhen there isevidence
ofdiseaseprogression(biochemically, radiographically
and/or symptomatically) in the presence of castrate
levels of testosterone (< 50ng/mLor < 1.7nmol/L).
3
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