©TheCanadian Journal ofUrology™: International Supplement, April 2014
Conclusions
Preserving skeletal integrity is a key component
of the management of advanced prostate cancer.
Indeed, the skeleton is theprimarydissemination site
for metastatic cells andADT, the reference systemic
treatment, profoundly affects bonephysiology.
The bone mineral density of patients receiving
ADT should be periodically checked by DXA scan,
especially if they carry additional risk factors for
osteoporosis. Lifestyleadjustments, includingweight-
bearingexercises, andappropriatecalcium-vitaminD
intakeshouldberecommended toeveryADTpatient.
Bisphosphonates or denosumab shouldbediscussed
in caseof osteoporosis.
In CRPC patients, bone is the most frequent
metastaticsite. Bonemetastasescangrowrapidlyand
cause debilitating complications. Bisphosphonates
or denosumab effectively delay these complications
and should be part of the standard armamentarium
in progressing metastatic CRPC patients. A careful
monitoring of patients, with a special attention on
calcium/vitamin D intake and oral hygiene, their
safety, is required to secure an acceptable toxicity
profile.
Basedon thecurrentevidence, there isno indication
of bisphosphonates or denosumab in bonemetastatic
hormone naïve or hormone responsive patients, or
in non-metastatic CRPC to prevent the onset of bone
metastases.
Disclosure
Dr. Valentina Butoescu has no potential conflict of
interest. Dr. BertrandTombal has receivedhonoraria
fromAmgen andFerring.
TABLE5.
Summaryofbonemetastasisprevention trial innon-metastaticprostatecancerpatients treatedwith
androgendeprivation therapy
Study
Patients
Treatment arms
Endpoints
MRCPR04
53
T
2-4
Clodronate
Time to symptomatic
Primarynotmet
versusplacebo
BMor prostate cancer
death,OS
Zometa 203
48
M0CRPC
ZAversusplacebo Time tofirst
Terminated early
BM,OS, BMFS
RADAR
T2a (Gleason EBRT+ADT±ADT PSA, PFS,OS, BMFS
Ongoing
≥ 7, PSA
≥ 10ng/mL);
orT
2b-4
,N
0
STAMPEDE
High risk
ADT+placeboor
OS,QoL, SREs, PFS
Ongoing
patients
ZAordocetaxel or
startingADT combination
ZEUS
Gleason 8-10;
ZAversus standard BM rate,OS, PSADT Primary notmet
pN
+
or PSA treatment
≥ 20ng/mL
M00-244
54
M0CRPC
Atrasentan
BMFS, PSA, PFS,OS
Primarynotmet
versusplacebo
EnthuseM0
55
M0CRPC
Zibotentan
BMFS,OS
Terminated early
versusplacebo
Study 147
49
M0CRPC
Denosumab
BMFS,OS
BMFS+ 4.2months
versusplacebo
fordenosumab
BM = bonemetastasis; BMFS = bonemetastasis free survival; EBRT = external beam radiotherapy; PFS = progression free
survival; ZA=zoledronicacid; ,DT=doubling time;OS=overall survival;QoL=quality-of-life; SRE= skeletal relatedevent
STAMPEDE includesM0 andM+patients
90
Practical guide tobonehealth in the spectrumof advancedprostate cancer
