©TheCanadian Journal ofUrology™: International Supplement, April 2014
is influenced by differences in assay tolerances,
lack of reference standards, and disparate sample
preparation.
45
Given theseproblems, cliniciansshould
be aware of the difficulty in interpreting individual
values, particularly if testing is performed in more
thanone laboratory. Thisapplies todatapresented in
thisreviewaswell,givenvaried testingplatformsand
variability that canoccurat low levelsof testosterone.
There are initiatives underway to develop testing
standards to allow equipment manufacturers to
calibrate equipment.
71
Current guidelines
Societyguidelinesregarding targetserum testosterone
levels inpatients onADT remainvague, likely owed
to the lack of level I evidence. The 2013 National
ComprehensiveCancerNetwork (NCCN) guidelines
define “adequate suppression”of serum testosterone
as<50ng/dLand is further reflected in theU.S. FDA
insert provided with LHRH therapies for prostate
cancer.
13
Additional hormonal manipulation is
recommended for patients who do not achieve this
levelwithcurrent therapies. TheAmericanUrological
Association (AUA) recently published guidelines on
the treatment of castration resistant prostate cancer
(CRPC)mentioning50ng/dLas thecutoff forcastrate
levels.
72
The most recent European Association
of Urology (EAU) guidelines question the need to
redefine the cut off from 50 ng/dL to 20 ng/dL on
the basis that a meta-analysis demonstrated similar
outcomes between LHRH agonists and orchiectomy
or DES at 2 years.
10,49
Arguably, better long term,
prospectively collected evidence is still needed.
Regular PSA and serum testosterone monitoring
shouldoccur forpatientsonADT. An increase inPSA
levels or the indicationof clinical progression should
trigger a testosterone level measurement in all cases
to confirm CRPC. If testosterone is inadequately
suppressed, secondary hormonal manipulation can
beundertaken.
44
Conclusions
Androgen deprivation continues to undergo
refinement and is a mainstay in the treatment of
advancedprostate cancer.
Disclosure
Dr. Kyle O. Rove has received honoraria from JP
Morgan and ZSAssociates.
Dr. E. David Crawford has received honoraria from
Bayer and Janssen.
References
1. Huggins C, Hodges C. Studies on prostate cancer: the effect
of castration, of estogen and of androgen injection on serum
phosphatases inmetastatic carcinoma of the prostate.
Cancer
Res
1941;1:293-297.
2. SchallyAV, ArimuraA, Baba Y et al. Isolation and properties
of the FSH and LH-releasing hormone.
Biochem Biophys Res
Commun
1971;43(2):393-399.
3. SchallyAV,ArimuraA,KastinAJetal.Gonadotropin-releasing
hormone:onepolypeptideregulatessecretionof luteinizingand
follicle-stimulatinghormones.
Science
1971;173(4001):1036-1038.
4. MontironiR,PomanteR,DiamantiLetal.Apoptosis inprostatic
adenocarcinoma following complete androgen ablation.
Urologia Int
1998;60(Suppl 1):25-30.
5. Tolis G, Ackman D, Stellos A et al. Tumor growth inhibition
in patients with prostatic carcinoma treatedwith luteinizing
hormone-releasing hormone agonists.
ProcNatl Acad Sci USA
1982;79(5):1658-1662.
6. The leuprolidestudygroup: leuprolideversusdiethylstilbestrol
for metastatic prostate cancer.
N Engl J Med
1984;311(20):
1281-1286.
7. Lin BJT, Chen K-K, Chen M-T et al. The time for serum
testosterone toreachcastrate levelafterbilateralorchiectomyor
oralestrogen in themanagementofmetastaticprostaticcancer.
Urology
1994;43(6):834-837.
8. OefeleinMG, FengA, Scolieri MJ et al. Reassessment of the
definition of castrate levels of testosterone: implications for
clinical decisionmaking.
Urology
2000;56(6):1021-1024.
9. NishiyamaT.Serum testosterone levelsaftermedicalorsurgical
androgendeprivation:acomprehensivereviewof the literature.
UrolOncol
2014;32(1):38.e17-28.
10.Heidenreich A, Bastian PJ, Bellmunt J et al. Guidelines on
prostatecancer.
EurUrol
2013:1-154.Availableat:http://www.
uroweb.org/gls/pdf/09_Prostate_Cancer_LR.pdf, accessed
September 22, 2013.
11.CassilethBR,VogelzangNJ, SolowayMSet al. Patients’ choice
of treatment instageDprostatecancer.
Urology
1989;33(Suppl5):
57-62.
12.Prostate Cancer Trialists’ Collaborative Group: Maximum
androgen blockade in advancedprostate cancer: an overview
of therandomised trials.ProstateCancerTrialists’Collaborative
Group.
Lancet
2000;355(9214):1491-1498.
13.Mohler JL, Armstrong AJ, Bahnson RR et al. NCCN clinical
practiceguidelines inoncology:prostatecancer.
NCCN.org
2013;
4.2013:1-79.
14.WidmarkA,KleppO,SolbergAetal.Endocrine treatment,with
or without radiotherapy, in locally advanced prostate cancer
(SPCG-7/SFUO-3): anopen randomisedphase III trial.
Lancet
2009;373(9660):301-308.
15.Mason MD, Parulekar W, Sydes MR et al. Final analysis
of intergroup randomized phase III study of androgen
deprivation therapy(ADT)plusradiationtherapy(RT) in locally
advancedprostatecancer (CaP).
JClinOncol
2012;30(Suppl15):
4509.
16.FrohmüllerHG,TheissM,ManseckAetal.Survivalandquality
of lifeofpatientswithstageD1 (T1-3pN1-2M0)prostatecancer.
Radical prostatectomy plus androgen deprivation versus
androgendeprivation alone.
EurUrol
1995;27(3):202-206.
17.GhavamianR,BergstralhEJ,BluteMLet al.Radical retropubic
prostatectomy plus orchiectomy versus orchiectomy alone
for ptxn+prostate cancer: amatched comparison.
JUrol
1999;
161(4):1223-1228.
18.GrimmMO, Kamphausen S, Hugenschmidt H et al. Clinical
OutcomeofPatientswithLymphNodePositiveProstateCancer
afterRadicalProstatectomyversusAndrogenDeprivation.
Eur
Urol
2002;41(6):628-634.
19
RoveandCrawford
