©TheCanadian Journal ofUrology™: International Supplement, April 2014
Addresscorrespondence toDr.E.DavidCrawford,Sectionof
UrologicOncology,Mail Stop#F710, P.O. Box6510,Aurora,
CO 80045USA
Traditional androgenablationapproaches to
advancedprostate cancer: new insights
KyleO. Rove,MD, E.DavidCrawford,MD
DivisionofUrology,UniversityofColorado,AnschutzMedicalCampus,Aurora, Colorado,USA
ROVEKO,CRAWFORDED. Traditional androgen
ablation approaches to advanced prostate cancer:
new insights.
Can JUrol
2014;21(Suppl 1):14-21.
Introduction:
Androgendeprivation therapy (ADT) is
amature therapy for the treatment of advanced prostate
cancer, and yet despite many years of use, there is still
much about its use, side effects, efficacy, and outcomes
forwhich theurologycommunitydoesnothaveanswers.
Materials and methods:
A literature search was
performedtoreviewADTuseinthemodernera,specifically
examining adjuvant ADT after primary therapy,
continuous versus intermittent ADT, disadvantages of
luteinizinghormonereleasinghormone (LHRH)agonists
versus newer LHRH antagonists, and controversies of
combined androgen blockade.
Results:
ADT has little role as primary therapy in
North American populations. Evidence for the use of
neoadjuvant/adjuvant ADTwith radical prostatectomy
is less compelling than that for radiation therapy. Data
supporting combined androgen blockade over LHRH
agonisttherapyalonearemixed. NewerLHRHantagonists
havea fasteronsetof reduction inserum testosteroneand
demonstrate other effects on serum follicle stimulating
hormone (FSH) that may impact prostate cancer
outcomes.
Conclusions:
ADT remains amainstay of treatment in
prostatecancer, andourknowledgeof itseffectivenesshas
improvedwith time. There are still scenarioswhere not
enough information is available and study is ongoing.
KeyWords:
androgendeprivation therapy,prostate
cancer,castrationresistantprostatecancer,androgen
receptor, CRPC
By eliminating ligand (namely serum testosterone),
this activity can be markedly downregulated as first
discoveredby theworkofHuggins andHodges,who
wereultimatelyawardedtheNobelPrize in1966.
1
Since
that time,bilateralorchiectomyhasbeenreplacedwith
medical alternatives, including luteinizing hormone
releasinghormone (LHRH) agonists, antagonists, and
combinedandrogenblockade(CAB). Theeffectofthese
regimens, however, is limited, as nearly all patients
withadvanceddiseasewill, ifmaintainedonandrogen
deprivationtherapy(ADT),developresistancerequiring
alternative therapies. Thisreviewexamines traditional
strategies to the use of androgen ablation in patients
withadvancedprostate cancer.
Introduction
Advanced prostate cancer arises in several forms,
either recognized because of rising prostate-specific
antigen (PSA) after failingprimary treatment or,more
ominously, bonepainorurinary symptoms signifying
locally advanced disease or metastasis. Fortunately,
the latter israre in themodernera. Allof theseentities,
however, are driven by ongoing stimulation and
downstreamsignalingfromtheandrogenreceptor(AR).
14
