Practical Guide for Bone Disease Control in the Prostate Cancer Patient

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Practical Guide for Bone Disease Control
in the Prostate Cancer Patient
Jiménez Ríos MÁ,1 Cortés Betancourt CR,2 Murphy Sánchez C,3 Manzanilla García HA,4


Pacheco Gahbler C,5 Figueroa Gómez R,6 Solares Sánchez ME 7

SUMMARY
Resumen
Prostate cancer (PCa) affects millions of adult men
El cáncer de próstata (CaP) afecta a millones de va-
worldwide and is considered one of the most im-
rones adultos en el mundo, por lo que se considera
portant neoplasias in terms of its morbidity and
una de las neoplasias más importantes en términos
mortality rates. Although diagnostic protocol is to
de sus tasas de morbilidad y mortalidad. Aunque
look for PCa at > 40 years of age, the majority of pa-
su diagnóstico se busca, por protocolo, desde los ?
tients presenting with it are > 60 years of age, and
40 años de edad, la mayoría de los pacientes tienen
their quality of life is seriously affected by the dis-
? 60 años, y su calidad de vida se ve seriamente
ease. Prostate cancer treatment is complex and it
afectada por el CaP. La terapéutica del CaP es com-
encompasses various pharmacological, radiologi-
pleja y en ella participan diversos recursos farma-
cal and surgical options. Most patients develop
cológicos, radiológicos y quirúrgicos. La mayoría de
hormone-dependent disease and are treated with a
los pacientes cursan con enfermedad hormono-
variety of anti-hormonal therapies, from pharma-
dependiente, por lo que reciben diversas terapias
cological castration to surgery. This approach has
antihormonales, que van de la castración farmaco-
a negative effect on bone metabolism and is con-
lógica a la quirúrgica. Este tipo de abordaje incide
ducive to malignant hypercalcemia (MHC), pain,
negativamente en el metabolismo óseo del paciente,
bone mineral density loss, vertebral compression
promoviendo hipercalcemia maligna (HCM), dolor,
and pathologic fractures. The patient ends up be-
pérdida de la densidad mineral ósea (DMO), com-
ing negatively affected by both the disease and the
presión vertebral y fracturas patológicas. Así, el pa-
treatment. Recently, the use of potent bisphos-
ciente con CaP es afectado tanto por la enfermedad
phonates has been shown to be a good alternative
como por el tratamiento de la misma. En años re-
for preventing Cancer Treatment-Induced Bone
cientes, el uso de bisfosfonatos potentes ha mostrado
Loss (CTIBL). Bisphosphonates reduce the rate of
ser un buen recurso para prevenir la Pérdida Ósea
Skeletal-Related Events (SREs) along with having
Inducida por el Tratamiento del Cáncer (CTIBL, por
a prophylactic effect on metastatic disease. More
sus siglas en inglés). Los bisfosfonatos disminuyen
1 Head of the Department of Urology at the National Cancer
at the Mexican Department of Health General Hospital, Mexi-
Institute (INCAN), Mexico City. 2 Head of the Urology Service
co City. 5 Staff Urologist of the Urology Service at the “Manuel
at the “20th of November” National Medical Center (CMN)
Gea González” General Hospital, Mexico City. 6 Urologist, An-
Specialty Hospital of the ISSSTE, Mexico City. 3 President of
geles Metropolitan Hospital, Mexico City. 7 Staff Urologist at
the Mexican Society of Urology. 4 Head of the Urology Service
the National Cancer Institute (INCAN), Mexico City.
Rev Mex Urol 2008; 68(1):44-48

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Jiménez RMÁ et al. Practical Guide for Bone Disease Control in the Prostate Cancer Patient
clinical studies need to be carried out to specifically
la tasa de Eventos Relacionados con el Esqueleto o
determine this effect. The following document is a
EREs, además de ejercer cierta actividad contra la
concise and current guide for bone disease treat-
afectación metastásica, lo cual debe aún precisarse
ment in PCa patients, put together by a group of
con la realización de más estudios clínicos. En este
Mexican urology specialists considered to be leaders
documento, un grupo de especialistas mexicanos en
in the field.
urología, considerados como líderes de opinión en
la materia, presenta una guía breve, pero actualiza-
Key Words: Prostate cancer, Bone mineral
da del manejo de la enfermedad ósea en los pacien-
density, Cancer treatment induced bone loss,
tes con CaP.
Bisphosphonates.
Palabras clave: cáncer de próstata, densidad mine-
ral ósea (DMO), pérdida ósea inducida por el trata-
miento del cáncer (CTIBL), bisfosfonatos.
first SRE about 10 months after diagnosis.1 Bone
OBJECTIVES
pain in these patients is generally difficult to local-
To establish basic guidelines for the clinical man-
ize and is more prominent at night. Effective pain
agement of Cancer Treatment-Induced Bone Loss
relief is the key to quality of life. Few therapies have
(CTIBL) in prostate cancer (PCa) patients, with the
categorically demonstrated metastatic PCa progres-
presentation of four algorithms for: 1) Preventive
sion retardation, making the preventive approach
CTIBL Treatment 2) Treatment of CTIBL-related
mandatory in symptomatic and asymptomatic pa-
Fracture 3) Androgenic Block Prostate Cancer
tients. The main treatment options include potent
Treatment and 4) Treatment of Metastatic Bone
bisphosphonate use, radiotherapy, and orthopedic
Disease in Symptomatic and Asymptomatic Hor-
and analgesic intervention.1
mone-Dependent PCa.
In the 1980’s, clinical studies began to include
specific studies in their trial protocol to evaluate PCa
METHODS
patient bone health with tools such as the bone
A group of distinguished Mexican urologists joined
scan. Later, N-telopeptide, bone-specific alkaline
forces to develop algorithms to serve as a clear and
phosphatase and peripheral bone densitometry
simple guide for clinical physicians in their man-
markers were developed. Presently, prostate-spe-
agement of the various stages in which bone me-
cific antigen levels are evaluated, since they can
tabolism is affected by the neoplasia as well as by
precede changes in bone scan by 7 to 12 months.2
its treatment.
TREATMENT
ANTECEDENTS AND RATIONALE
Today, bone evaluation is a necessary part of the
Experience and clinical trials on PCa treatment
PCa therapeutic approach. From the time of diag-
have shown that acute effects of Skeletal Related
nosis itself, an effort is made to prevent all skeletal-
Events (SREs) have a statistically significant nega-
related events that can be present in PCa patients,
tive impact on bone health and the quality of life
from malignant hypercalcemia to the development
of patients at different stages of PCa development.
of metastatic disease.
This translates into pain and functional loss or in-
capacity and leads the patient towards greater risk
The following algorithm shows the preventive
of short- and long-term skeletal morbidity. On the
management of PCa-associated bone loss and its
average, the metastatic PCa patient will suffer his
treatment (Algorithm 1).
Rev Mex Urol 2008; 68(1):44-48
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Jiménez RMÁ et al. Practical Guide for Bone Disease Control in the Prostate Cancer Patient
Algorithm 1. Preventive Management of Bone Loss Associated with Prostate Cancer Hormonal Treatment.
Clinical Presentation
Research
Management
Lifestyle changes
• Zoledronic Acid
• Pamidronate
• Alendronate
Make sure there is
• Clodronate
T- score
BMD
adequate calcium
and vitamin intake
<-2.5
DEXA
Densitometry
(osteoporosis)
• Hip
• Radius
Fracture risk
• Repeat Lumbar
spine reading
factors
-1 to -2.5
Repeat DMO
(osteopenia)
Reading after 6-12
• ADT
QCT
• Future fracture
Lumbar spine
-1
Repeat DMO
(normal)
reading ? 2 years
(Am J Health-Syst, Pharm © 2006. American Society of Health-System Pharmacists)
Algorithm 2. Metastatic Bone Disease Management in Symptomatic and Asymptomatic Hormone –Dependent PCa Patients (BAUS).
Bone Metastasis Under
Androgenic Blockade
QT, Zoledronic Acid, Others
Asymptomatic
Symptomatic
Vertebral Instability
Supervision
Relief
Orthopedic Intervention
Pain Clinic
Radiotherapy
Palliative Care
Supervision
Pain is a cardinal symptom in the PCa treatment
Algorithm 2 illustrates the preventive management
approach. A patient who has not been diagnosed
of symptomatic and asymptomatic patients pre-
with this neoplasia but who complains of bone
senting with hormone-dependent PCa, hormone
pain should be immediately tested to establish or
treatment-induced bone loss and metastatic dis-
rule-out PCa diagnosis. A distinction between hor-
ease. This approach attempts to relieve pain and
mone-dependent and hormone-refractory disease
prevent the development of all subsequent bone
must be determined in patients diagnosed with PCa.
complications, including metastases.
44 Rev Mex Urol 2008; 68(1):44-48

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Jiménez RMÁ et al. Practical Guide for Bone Disease Control in the Prostate Cancer Patient
Algorithm 3. Management of the CTIBL-prompted Fracture Patient.
Clinical Presentation
Research
Management
Bone mass loss
Any fracture
X-Rays
Lifestyle changes
treatment with
occuring after
Confirmation of
Densitometry
hormonal blockade
minimum trauma
fracture
Make sure there is
adequate calcium
to prevent future
and vitamin intake
fractures
Suspicion of
• Zoledronic Acid
fracture
• Pamidronate
• Alendronate
• Clodronate
(Am J Health-Syst, Pharm © 2006. American Society of Health-System Pharmacists)
Algorithm 4. Prostate Cancer Treatment with Androgen Blockade.
High
Bone Markers
N Telopeptid
AF bone specific
Calcium
Normal
D Vitamin
with hormonal
Zoledronic
treatment
acid
T-Score
from +1 to -1
Periferic
bone
To value
densitometry
androgenic
T-Score
blockade
Prostatic cancer
from -1 to <-2.5
local y advanced
High
Specific
Supervision
prostatic
antigen
Normal
Without
hormonal treatment
T-Score
Control
Periferic
from +1 to -1
bone
densitometry
T-Score
Calcium
from -1 to <-2.5
D vitamin
Obviously, the so-called pathologic fractures in
acid (ZA) and other options such as radiation and
PCa patients are the worst CTIBL consequences -
isotope administration have been shown to diminish
with the exception of bone metastases - at the bone
pain and bone complications in general, none of
metabolism level. Metastatic hormone-dependent
these alternatives has been objectively proven to
PCa patients have a poor survival prognosis of 9 to
increase survival rate. The following chart for Algo-
12 months. The presence of metastasis significantly
rithm 3 illustrates fracture management.
increases morbidity, promotes fractures, anemia,
Algorithm 4 illustrates the management of PCa
cachexia, pain and vertebral compression. Even
patients who receive hormone therapy and of those
though potent bisphosphonates such as zoledronic
who do not. In hormone-refractory PCa patients,
Rev Mex Urol 2008; 68(1):44-48
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Jiménez RMÁ et al. Practical Guide for Bone Disease Control in the Prostate Cancer Patient
the prognostic death factors that have been identi-
BIBLIOGRAPHY
fied up to now are hemoglobin, alkaline phosphate,
bladder disease and performance status. 3
1. Berruti A, Dogliotti L, et al. Incidence of skeletal com-
plications in patients with bone metastatic prostate
CONCLUSIONS
cancer and hormone refractory disease. J Urol. 2000;
164: 1248-1253.
In the United States, PCa is the most commonly
diagnosed malignant tumor and is the third most fre-
2. Petrylak DP. Docetaxel for the treatment of hormone
quent cause of death in men.4 Ten years ago, Mohar
refractory prostate cancer. Rev Urol. 2003; 5 (suppl 2):
514 – 21.
and colleagues 5 became aware of the relevance of
this neoplasia in Mexico, which a decade ago had
3. Lucas A, Petrylak DP. The case for early chemotherapy
only been surpassed by testicular cancer, lung can-
for the treatment of metastatic disease. J Urol 2006.
Dec; 176 (6 Pt 2):572-5.
cer and non-Hodgkin lymphoma. This has been
changing, and more and more, national incidence
4. Hortobagyi G. Progress in the management of bone
rates resemble those of the industrialized coun-
metastases: one continent at a time? J Clin Oncol.
2005; 23(15): 2399-3301.
tries. Therefore it is tremendously important for
specialists to have a therapeutic approach which
5. Alejandro Mohar, Mauricio Frías-Mendivil et al. Epi-
facilitates patient management at each stage of the
demiología descriptiva de cáncer en el Instituto Na-
cional de Cancerología de México. Salud Pública Mex
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1997; Vol. 39(4): 253-258.
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Document Outline

• 00-EDITORIAL.pdf
• 127.pdf
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• 158.pdf
• 149-.pdf
• 102.pdf
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