KEY CONCEPTS

Prostate cancer is the most frequent cancer in United States men.

African-American ancestry, family history, and increased age
are the primary risk factors for prostate cancer.
Prostate-specic antigen is a useful marker for detecting
prostate cancer at early stages, predicting outcome for local-
ized disease, dening disease-free status, and monitoring
response to androgen-deprivation therapy or chemotherapy
for advanced-stage disease.
The prognosis for prostate cancer patients depends on the his-
tologic grade, the tumor size, and the disease stage. More than
85% of patients with stage A
1
disease but less than 1% of those
with stage D
2
can be cured.
Androgen ablation with a luteinizing hormonereleasing hor-
mone (LHRH) agonist plus an antiandrogen should be used prior
to radiation therapy for patients with locally advanced prostate
cancer to improve outcomes over radiation therapy alone.
Androgen ablation therapy, with either orchiectomy, a
luteinizing hormonereleasing hormone (LHRH) agonist
alone, or an LHRH agonist plus an antiandrogen (combined
hormonal blockade), can be used to provide palliation for
patients with advanced (stage D
2
) prostate cancer. The effects
of androgen deprivation seem most pronounced in patients
with minimal disease at diagnosis.
Antiandrogen withdrawal, for patients having progressive dis-
ease while receiving combined hormonal blockade with a
luteinizing hormonereleasing hormone (LHRH) agonist plus
an antiandrogen, can provide additional symptomatic relief.
Mutations in the androgen receptor have been documented that
cause antiandrogen compounds to act like receptor agonists.
Chemotherapy, with docetaxel and prednisone or docetaxel
and estramustine, improves survival in patients with hormone-
refractory prostate cancer. Patients with hormone-refractory
prostate cancer should be considered for entry into clinical tri-
als investigating new therapies for prostate cancer.
89 PROSTATE CANCER
Jill M. Kolesar
LEARNING OBJECTIVES
UPON COMPLETION OF THE CHAPTER, THE READER WILL BE ABLE TO:
1. Describe the incidence and mortality of prostate cancer.
2. List the risk factors associated with the development of prostate cancer.
3. Understand the pathophysiology underlying the clinical symptoms associated with
prostate cancer.
4. Compare placebo versus nasteride for the prevention of prostate cancer.
5. Recommend a prostate cancer screening program for a man based on his age and risk factors.
6. Recommend a treatment for initial treatment of prostate cancer based on stage, Gleason
score, age, and symptoms.
7. Compare the efcacy of radiation therapy versus surgical therapy for the initial
management of prostate cancer.
8. Outline the role of luteinizing hormonereleasing hormone (LHRH) agonists in the
treatment of prostate cancer.
9. Contrast the benets and risks of luteinizing hormonereleasing hormone (LHRH) single-
agent therapy and combined androgen blockade in the rst-line therapy of metastatic
prostate cancer.
10. Understand the role of chemotherapy in the treatment of metastatic prostate cancer.
1357
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1358 SECTION 16 / ONCOLOGIC DISORDERS
Prostate cancer is the most commonly diagnosed cancer in
American men.
1
For most men, prostate cancer has an indo-
lent course, and treatment options for early disease include
expectant management, surgery, and radiation. With expectant
management, patients are monitored for disease progression
or development of symptoms. Localized prostate cancer can be
cured by surgery or radiation therapy, but advanced prostate
cancer is not yet curable. Treatment for advanced prostate can-
cer can provide signicant disease palliation for many patients
for several years after diagnosis. The endocrine dependence of
this tumor is well documented, and hormonal manipulation to
decrease circulating androgens remains the basis for the treat-
ment of advanced disease.
EPIDEMIOLOGY AND ETIOLOGY
Prostate cancer is the most frequent cancer among
American men and represents the second leading cause of can-
cer-related deaths in all males.
1
In the United States alone, it is
estimated that 234,460 new cases of prostatic carcinoma will
be diagnosed and more than 27,350 men will die from this
disease in 2006.
1
Although prostate cancer incidence increased
during the late 1980s and early 1990s owing to widespread
prostate-specic antigen (PSA) screening, deaths from
prostate cancer have been declining continuously since 1995.
1
Table 891 summarizes the possible factors associated
with prostate cancer.
2
The only widely accepted risk factors for
prostate cancer are age, race/ethnicity, and family history of
prostate cancer.
2
The disease is rare under the age of 40 years, but
the incidence increases sharply with each subsequent decade,
most likely because the individual has had a lifetime exposure to
testosterone, a known growth signal for the prostate.
3
Race and Ethnicity
The incidence of clinical prostate cancer varies across geo-
graphic regions. Scandinavian countries and the United States
report the highest incidence of prostate cancer, whereas the dis-
ease is relatively rare in Japan and other Asian countries.
4
African-American men have the highest rate of prostate cancer
in the world, and in the United States, prostate cancer mortal-
ity in African Americans is more than twice that seen in
Caucasian populations.
1
Hormonal, dietary, and genetic differ-
ences, as well as differences in access to health care, may con-
tribute to the altered susceptibility to prostate cancer in these
populations.
2
Testosterone, commonly implicated in the patho-
genesis of prostate cancer, is 15% higher in African American
men than in Caucasian males. Activity of 5--reductase, the
enzyme that converts testosterone to its more active form, dihy-
drotestosterone (DHT), in the prostate, is decreased in Japanese
men compared with African Americans and Caucasians.
2
In
addition, genetic variations in the androgen receptor exist.
Activation of the androgen receptor is inversely correlated with
CAG repeat length. Shorter CAG repeat sequences have been
found in African Americans. Therefore, the combination of
increased testosterone and increased androgen receptor activation
may account for the increased risk of prostate cancer for African-
American men.
2
The Asian diet generally is considered to be low
in fat and high in ber with a high concentration of phytoestro-
gens, potentially explaining the decreased risk in Asians.
4
Family History
There appears to a be a family prostate cancer syndrome and
genome-wide scans have identied potential prostate cancer
susceptibility loci on chromosomes 1, 2q, 12p, 15q, 16p, and
TABLE 891. Risk Factors Associated with Prostate Cancer
Factor Possible Relationship
Probable Risk Factors
Age More than 70% of cases are
diagnosed in men greater than
65 years old.
Race African Americans have higher
incidence and death rate.
Genetic Familial prostate cancer is inherited
in an autosomal dominant
manner.
Mutations in p53, Rb, E-cahedrin,
a-catenin, androgen receptor,
KAII, microsatellite instability,
loss of heterozygocity at 1, 2q,
12p, 15q, 16p, and 16q.
Candidate prostate cancer gene
locus identied on chromosome 1.
Possible Risk Factors
Environmental Clinical carcinoma incidence varies
worldwide.
Latent carcinoma similar between
regions. Nationalized males
adopt intermediate incidence
rates between that of the United
States and their native country.
Occupational Increased risk associated with
cadmium exposure.
Diet Increased risk associated with
high-meat and high-fat diets.
Decreased intake of 1,
25-dihydroxyvitamin D, vitamin E,
lycopene, and b-carotene
increases risk.
Hormonal Does not occur in eunuchs.
Low incidence in cirrhotic patients.
Up to 80% are hormonally dependent.
African-Americans have
15% increased testosterone.
Japanese have decreased
5-a-reductase activities.
Polymorphic expression of the
androgen receptor.
Compiled from Carter et al,
2
Hsieh et al,
3
and Ross et al.
4
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CHAPTER 89 / PROSTATE CANCER 1359
16q; however, none of these susceptibility loci have demon-
strated linkage to currently known candidate genes.
5
An alternative explanation for the familial clustering may be
polymorphisms in genes important for prostate cancer func-
tion and development.
5
Candidate polymorphisms include a
polymorphism in the androgen receptor, which has two differ-
ent nucleotide repeat variants, the CAG and the GCC. The
CAG repeat varies in repeat number from 11 to 31 repeats in
healthy individuals, and the number of repeats is inversely
proportional to the activity of the androgen receptor. Some
studies have demonstrated that shorter CAG repeats are asso-
ciated with increased prostate cancer risk. Another candidate
polymorphism is SRD5A2, which is the gene that codes for
5--reductase, the enzyme that converts testosterone to the
more active dihydrotestosterone. A variant in SRD5A2, the
Ala49Thr, increases the activity and may increase prostate
cancer risk.
5
Diet
A number of epidemiologic studies support an association
between high fat intake and the risk of prostate cancer. A
strong correlation between national per capita fat consump-
tion and national prostate cancer mortality has been reported,
and prospective case-control studies suggest that a high-fat
diet doubles the risk of prostate cancer.
Other dietary factors implicated in prostate cancer include
retinol, carotenoids, lycopene, and vitamin D consumption.
5,6
Retinol, or vitamin A, intake, especially in men older than age
70, is correlated with an increased risk of prostate cancer,
whereas intake of its precursor, -carotene, has a protective or
neutral effect. Lycopene, obtained primarily from tomatoes,
decreases the risk of prostate cancer in small cohort studies. The
antioxidant vitamin E also may decrease the risk of prostate
cancer. Men who developed prostate cancer in one cohort study
had lower levels of 1,25(OH)
2
-vitamin D than matched con-
trols, although a prospective study did not support this.
2
Clearly, dietary risk factors require further evaluation, but
because fat and vitamins are modiable risk factors, dietary
intervention may be promising in prostate cancer prevention.
Other Factors
Benign prostatic hyperplasia (BPH) is one of the most com-
mon problems of elderly men, affecting more than 40% of
men over age 70. BPH results in the urinary symptoms of hes-
itancy and frequency. Since prostate cancer affects a similar
age group and often has similar presenting symptoms, the
presence of BPH often complicates the diagnosis of prostate
cancer, although it does not appear to increase the risk of
developing prostate cancer.
2,5
Smoking has not been associated with an increased risk of
prostate cancer, but smokers with prostate cancer have an
increased mortality resulting from the disease when compared
with nonsmokers with prostate cancer [relative risk (RR) =
1.52).
2,5
In addition, in a prospective cohort analysis, alcohol
consumption was not associated with the development of
prostate cancer.
Chemoprevention
Currently, the most promising agent for the prevention of
prostate cancer is nasteride, a 5--reductase inhibitor used for
BPH.
6
When compared with placebo, the point prevalence of
prostate cancer was reduced for those on nasteride by 24.8%
[95% condence interval (CI) = 18.630.6%; hazard ratio (HR) =
0.75]. However, in those who did develop prostate cancer,
there was an increase in the number of high-grade (Gleason
grade 710) tumors detected at biopsy in the nasteride group.
Overall, nasteride did reduce the frequency of prostate cancer,
but the prostate cancers that were diagnosed in the nasteride
group were more aggressive.
Therefore, the use of nasteride to prevent prostate cancer
is currently under debate.
7
Because of its established benet in
treating BPH, the 20% to 30% of men over age 50 with BPH
may derive the additional benet of prostate cancer preven-
tion and should be offered treatment with nasteride. In the
70% to 80% of men without BPH, the benets, side effects
(primarily impotence), and risks of nasteride should be dis-
cussed prior to initiating therapy.
Other agents, including selenium, vitamin E, lycopene,
green tea, nonsteriodal anti-inammatory agents, isoavones,
and statins, are under investigsation for prostate cancer and
show promise. Selenium is a naturally occurring trace element
that is an essential nutrient in the human diet.
8
However, none
of these agents is currently recommended for routine use out-
side a clinical trial.
Screening
Early detection of potentially curable prostate cancers is the
goal of prostate cancer screening. For cancer screening to be
benecial, it must reliably detect cancer at an early stage,
when intervention would decrease mortality. Whether
prostate cancer screening ts these criteria has generated
considerable controversy.
9
Digital rectal examination (DRE)
has been recommended since the early 1900s for the detec-
tion of prostate cancer. The primary advantage of DRE is its
specicity, reported at greater than 85%, for prostate cancer.
Other advantages of DRE include low cost, safety, and ease of
performance. However, DRE is relatively insensitive and is
subject to interobserver variability. DRE as a single screening
method has poor compliance and has had little effect on pre-
venting metastatic prostate cancer in one large case-control
study.
10
Prostate-specic antigen (PSA) is a useful marker for detect-
ing prostate cancer at early stages, predicting outcome for localized
disease, dening disease-free status, and monitoring response to
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1360 SECTION 16 / ONCOLOGIC DISORDERS
androgen-deprivation therapy or chemotherapy for advanced-stage
disease. PSA is used widely for prostate cancer screening in the
United States, with simplicity its major advantage and low speci-
city its primary limitation.
11
PSA may be elevated in men with
acute urinary retention, acute prostatitis, and prostatic ischemia
or infarction, as well as BPH, a nearly universal condition in men
at risk for prostate cancer. PSA elevations between 4.1 and 10
ng/mL (10 mcg/L) cannot distinguish between BPH and prostate
cancer, limiting the utility of PSA alone for the early detection of
prostate cancer. Additionally, only 38% to 48% of men with clin-
ically signicant prostate cancer have a serum PSA outside the
reference range.
12
Neither DRE nor PSA is sensitive or specic enough to be
used alone as a screening test.
12
Although the relative pre-
dictability of DRE and PSA is similar, the tumors identied by
each method are different. Catalona and associates
13
conrmed
that the combination of a DRE and a PSA determination is a
better method of detecting prostate cancer than DRE alone.
The common approach to prostate cancer screening today
involves offering a baseline PSA and DRE at age 40, with
annual evaluations beginning at age 50, to all men of normal
risk with a 10-year or greater life expectancy.
Despite this common practice, the benets of prostate can-
cer screening are unproven. PSA measurements can identify
small, subclinical prostate cancers, where no intervention may
be required. Detecting prostate cancer in those not needing
therapy not only increases the cost of care through unneces-
sary screening and work-ups but also increases the toxicity of
therapy by subjecting some patients to unnecessary therapy.
14
Currently, the American College of Physicians recommends
that rather than screening all men for prostate cancer as a
matter of routine, physicians should describe the potential
benets and known risks of screening, diagnosis, and treat-
ment; listen to the patients concerns; and then decide on an
individuals screening method.
PATHOPHYSIOLOGY
The growth and development of the prostate is under control
of androgens, and it is well known that men who undergo cas-
tration prior to puberty do not develop prostate cancer. The
majority of risk factors for prostate cancer are factors that
either increase or decrease testosterone exposure. Despite this,
serum testosterone or DHT levels obtained at diagnosis are
not associated directly with prostate cancer risk, suggesting a
multifactorial cause of prostate cancer.
5
The normal prostate is composed of acinar secretory cells
arranged in a radial shape and surrounded by a foundation of
supporting tissue. The size, shape, or presence of acini are
almost always altered in the gland that has been invaded by
prostatic carcinoma. Adenocarcinoma, the major pathologic
cell type, accounts for more than 95% of prostate cancer
cases.
15
Much rarer tumor types include small cell neuroen-
docrine cancers, sarcomas, and transitional cell carcinomas.
Prostate cancer can be graded systematically according to
the histologic appearance of the malignant cell and then
grouped into well, moderately, or poorly differentiated
grades.
16
Gland architecture is examined and then rated on a
scale of 1 (well differentiated) to 5 (poorly differentiated). Two
different specimens are examined, and the score for each spec-
imen is added. Groupings for total Gleason score are 2 to 4 for
well-differentiated, 5 or 6 for moderately differentiated, and 7 to
10 for poorly differentiated tumors. Poorly differentiated tumors
grow rapidly (poor prognosis), whereas well-differentiated
tumors grow slowly (better prognosis).
Metastatic spread can occur by local extension, lymphatic
drainage, or hematogenous dissemination.
17
Lymph node
metastases are more common in patients with large, undifferen-
tiated tumors that invade the seminal vesicles. The pelvic and
abdominal lymph node groups are the most common sites of
lymph node involvement (Fig. 891). Skeletal metastases from
hematogenous spread are the most common sites of distant
Patient Encounter 1
HG is 46-year-old Caucasian man. He is not overweight and
follows a low-fat diet. He does not have any family members
with a history of prostate cancer.
What are his options for prostate cancer screening?
Is he a candidate for prostate cancer chemoprevention?
What are his risk factors for prostate cancer?
FIGURE 891. The prostate gland. (From Kolesar JM. Prostate
cancer. In: DiPiro JT, Talbert RL, Yee GC, et al, (eds.)
Pharmacotherapy: A Pathophysiologic Approach. 6th ed.
New York: McGraw-Hill; 2005: 2423.)
Urinary
bladder
Lateral sacral
nodes
Hypogastric
nodes
Prostate
External
iliac nodes
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CHAPTER 89 / PROSTATE CANCER 1361
spread. Typically, the bone lesions are osteoblastic or a combina-
tion of osteoblastic and osteolytic. The most common site of
bone involvement is the lumbar spine. Other sites of bone
involvement include the proximal femurs, pelvis, thoracic spine,
ribs, sternum, skull, and humerus. The lung, liver, brain, and
adrenal glands are the most common sites of visceral involve-
ment, although, these organs usually are not involved initially.
About 25% to 35% of patients will have evidence of lymphan-
gitic or nodular pulmonary inltrates at autopsy. The prostate is
a rare site for metastatic involvement from other solid tumors.
The prostate gland is a solid, round, heart-shaped organ
positioned between the neck of the bladder and the urogenital
diaphragm (see Fig. 891). Normal growth and differentiation
of the prostate depend on the presence of androgens, speci-
cally DHT.
18
The testes and the adrenal glands are the major
sources of circulating androgens. Hormonal regulation of
androgen synthesis is mediated through a series of biochemi-
cal interactions between the hypothalamus, pituitary, adrenal
glands, and testes (Fig. 892). Luteinizing hormonereleasing
hormone (LHRH) released from the hypothalamus stimulates
the release of luteinizing hormone (LH) and follicle-stimulat-
ing hormone (FSH) from the anterior pituitary gland. LH
complexes with receptors on the Leydig cell testicular mem-
brane and stimulates the production of testosterone and small
amounts of estrogen. FSH acts on the Sertoli cells within the
testes to promote the maturation of LH receptors and to pro-
duce an androgen-binding protein. Circulating testosterone
and estradiol inuence the synthesis of LHRH, LH, and FSH
by a negative-feedback loop operating at the hypothalamic and
pituitary level.
19
Prolactin, growth hormone, and estradiol
appear to be important accessory regulators for prostatic tissue
permeability, receptor binding, and testosterone synthesis.
Testosterone, the major androgenic hormone, accounts for
95% of the androgen concentration. The primary source of
testosterone is the testes; however, 3% to 5% of the testosterone
concentration is derived from direct adrenal cortical secretion
of testosterone or C-19 steroids such as androstenedione.
17,18
Hormonal manipulations to ablate or reduce circulating
androgens can occur through several mechanisms
17,18
(Table 892). The organs responsible for androgen production
can be removed surgically (e.g., orchiectomy, hypophysectomy,
or adrenalectomy). Hormonal pathways that modulate prosta-
tic growth can be interrupted at several steps (see Fig. 892).
Interference with LHRH or LH can reduce testosterone secre-
tion by the testes (e.g., estrogens, LHRH agonists, progestogens,
and cyproterone acetate). Estrogen administration reduces
androgens by directly inhibiting LH release, by acting directly
on the prostate cell, or by decreasing free androgens by increas-
ing steroid-binding globulin levels.
17,18
Isolation of the naturally occurring hypothalamic decapep-
tide hormone LHRH has provided another group of effective
agents for advanced prostate cancer treatment.
20
The physio-
logic response to LHRH depends on both the dose and mode of
administration. Intermittent pulsed LHRH administration,
which mimics the endogenous release pattern, causes sustained
release of both LH and FSH, whereas high-dose or continuous
intravenous administration of LHRH inhibits gonadotropin
release owing to receptor down-regulation.
19
Structural modi-
cation of naturally occurring LHRH and innovative delivery
have produced a series of LHRH agonists that cause a similar
down-regulation of pituitary receptors and a decrease in testos-
terone production.
19
FIGURE 892. Hormonal regulation of the prostate gland.
ACTH, adrenocorticotropic hormone; DHT, dihydrotestos-
terone; FSH, follicle-stimulating hormone; GH, growth hor-
mone; LH, luteinizing hormone; LHRH, luteinizing
hormonereleasing hormone; PROL, prolactin; R, receptor.
(From Kolesar JM. Prostate cancer. In DiPiro JT, Talbert RL, Yee
GC, et al, (eds.) Pharmacotherapy: A Pathophysiologic
Approach. 6th ed. New York: McGraw-Hill; 2005: 2424.)
DNA RNA
mRNA
Prostate cell
R R
DHT
DHT DHT
Androgens
Androgens
Testosterone
Testosterone
R
TABLE 892. Hormonal Manipulations in Prostate Cancer
Androgen source ablation Antiandrogens
Orchiectomy Flutamide
Adrenalectomy Bicalutamide
Hypophysectomy Nilutamide
LHRH or LH inhibition Cyproterone acetate
b
Estrogens Progesterones
LHRH agonists 5--reductase inhibition
Progesterones
a
Finasteride
b
Cyproterone acetate
b
Androgen synthesis inhibition
Aminoglutethimide
Ketoconazole
Progesterones
a
a
Minor mechanisms of action.
b
Investigational compounds or use.
LH, luteinizing hormone; LHRH, luteinizing hormonereleasing hormone.
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1362 SECTION 16 / ONCOLOGIC DISORDERS
Androgen synthesis can be inhibited in the testes or in the adre-
nal gland. Aminoglutethimide inhibits the desmolase-enzyme
complex in the adrenal gland, thereby preventing the conversion of
cholesterol to pregnenolone. Pregnenolone is the precursor sub-
strate for all adrenal-derived steroids, including androgens, gluco-
corticoids, and mineralocorticoids.
21
Ketoconazole, an imidazole
antifungal agent, causes a dose-related reversible reduction in
serum cortisol and testosterone concentration by inhibiting both
adrenal and testicular steroidogenesis.
21,22
As a secondary mecha-
nism to its antiandrogen action, megestrol acetate inhibits the syn-
thesis of androgens. This inhibition appears to occur at the adrenal
level, but circulating levels of testosterone also are reduced, sug-
gesting that inhibition at the testicular level also may occur.
21
Antiandrogens inhibit the formation of the DHT-receptor
complex and thereby interfere with androgen-mediated action
at the cellular level.
22
Megestrol acetate, a progestational agent,
also is available and has antiandrogen actions.
21
Finally, the
conversion of testosterone to DHT may be inhibited by 5--
reductase inhibitors.
6
CLINICAL PRESENTATION, DIAGNOSIS,
AND STAGING
The information obtained from the diagnostic tests is used to
stage the patient. There are two commonly recognized staging
classication systems (Table 893). The formal international
classication system [tumor, node, metastases (TNM)], adopted
by the International Union Against Cancer in 1974, was updated
in 1992 in an effort to provide congruence with the classic
American Urologic System (AUS) staging system for prostate
cancer.
23
The AUS classication is the most commonly used
staging system in the United States (see Table 893). Patients are
assigned to stages A through D and corresponding subcategories
based on size of the tumor (T), local or regional extension, pres-
ence of involved lymph node groups (N), and presence of
metastases (M).
23
Some studies classify patients who have pro-
gressed after hormonal therapy as stage D
3
.
38
Based on men
diagnosed with prostate cancer at Walter Reed Army Medical
Center from 1988 to 1998, including over 2042 prostate cancer
diagnoses, localized prostate cancer (stage T
1
and T
2
) was diag-
nosed more frequently (89% versus 68%) and advanced disease
(stages T
3
, T
4
, and D) was diagnosed less frequently (11% versus
32%) when comparing the 1998 to the 1988 incidence rates.
The prognosis for patients with prostate cancer depends on
the histologic grade, the tumor size, and the local extent of the
primary tumor.
16
The most important prognostic criterion
appears to be the histologic grade because the degree of dif-
ferentiation ultimately determines the stage of disease. Poorly
differentiated tumors are highly associated with both regional
lymph node involvement and distant metastases.
16
Between 1992 and 1999, 5-year overall survival rates were
estimated at 98% for whites and 93% for African Americans.
1
For this same period, the survival rates for localized or regional
disease (100%) and distant disease (33%) in white males were
about the same as the survival rates for localized or regional dis-
ease (100%), and distant disease (26%) in African Americans.
1
A
6.3% decline in age-adjusted mortality has been documented
for the period 1991 to 1995.
24
Ten-year cancer-specic survival
is estimated as 95% for stage A
1
, 80% for stages A
2
to B
2
, 60% for
stage C, 40% for stage D
1
, and 10% for stage D
2
.
25
It is estimated
that more than 85% of patients with stage A
1
can be cured,
whereas fewer than 1% of patients with stage D
2
will be cured.
Clinical Presentation
Localized Disease
Asymptomatic
Locally Invasive Disease
Ureteral dysfunction, frequency, hesitancy, and dribbling
Impotence
Advanced Disease
Back pain
Cord compression
Lower extremity edema
Pathologic fractures
Anemia
Weight loss
Diagnostic and Staging Work-Up for
Prostate Cancer
Diagnostic Tests
Digital rectal examination (DRE)
Prostate-specic antigen (PSA)
Transrectal ultrasonography (TRUS) if either DRE is posi-
tive or PSA is elevated
Biopsy
Staging Tests
Gleason score on biopsy specimen
Bone scan
Complete blood count
Liver function tests
Serum phosphatases (acid/alkaline)
Excretory urogram
Chest x-ray
Additional Staging Tests
Depends on tumor classication, PSA, and Gleason score.
Skeletal lms
Lymph node evaluation
Pelvic computed tomography

111
In-labeled capromab pendetide scan
Bipedal lymphangiogram
Transrectal magnetic resonance imaging
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CHAPTER 89 / PROSTATE CANCER 1363
TREATMENT
Desired Outcome
The desired outcome in early-stage prostate cancer is to min-
imize morbidity and mortality owing to prostate cancer.
26
Unfortunately, the most appropriate therapy for early-stage
prostate cancer is unknown. Early-stage disease may be
treated with surgery, radiation, or watchful waiting. While
surgery and radiation are curative, they are associated with
signicant morbidity and mortality. Since the overall goal is to
minimize morbidity and mortality associated with the dis-
ease, watchful waiting is appropriate in selected individuals.
Advanced prostate cancer (stage D) is not currently curable,
and treatment should focus on providing symptom relief and
maintaining quality of life.
27
General Approach to Treatment
The initial treatment for prostate cancer depends primarily on
the disease stage, the Gleason score, the presence of symptoms,
and the life expectancy of the patient.
15,26
Prostate cancer usually
TABLE 893. Staging and Classication Systems for Prostate Cancer
AUS
a
Stage (AD) AJC-UICC
b
Classication (TNM)
A (occult, nonpalpable) T
x
N
x
M
x
(cannot be assessed)
T
0
N
0
M
0
(nonpalpable)
A
1
: Focal T
0
: Focal or diffuse
A
2
: Diffuse
B (conned to prostate) T
1
N
0
M
0
, T
2
N
0
M
0
B
1
: Single nodule in one lobe,
less than 1.5 cm T
1
: (Clinically inapparent tumor not palpable or visible
by imaging)
T
1a
: Tumor incidental histologic nding in 5% or less
of tissue resected
T
1b
: Tumor incidental histologic nding in 5% or more
of tissue resected
T
1c
: Tumor identied by needle biopsy (e.g., because
of elevated PSA)
B
2
: Diffuse involvement of whole gland, T
2
: (Tumor conned within the prostate
c
)
greater than 1.5 cm T
2a
: Tumor involves half of a lobe or less
T
2b
: Tumor involves more than half a lobe, but not
both lobes
T
2c
: Tumor involves both lobes
C (localized to periprostatic area) T
3
N
0
M
0
, T
4
N
0
M
0
C
1
: No seminal vesicle involvement, T
3
: (Tumor extends through the prostatic capsule
d
)
less than 70 g T
3a
: Unilateral extracapsular extension
T
3b
: Bilateral extracapsular extension
T
3c
: Tumor invades the seminal vesicle(s)
C
2
: Seminal vesicle involvement, T
4
: (Tumor is xed or invades adjacent structures
greater than 70 g other than the seminal vesicles)
T
4a
: Tumor invades any of bladder neck, external
sphincter, or rectum
T
4b
: Tumor invades levator muscles and/or is xed to
the pelvic wall
D (metastatic disease) Any T, N
14
, M
0
, or N
04
, M
1
D
1
: Pelvic lymph nodes or ureteral N
1
: Metastasis in a single lymph node, 2 cm or
obstruction less in greatest dimension
D
2
: Bone, distant lymph node, organ, N
2
: Metastasis in single lymph node more than 2 cm
or soft tissue metastases but not more than 5 cm in greatest dimension, or
multiple lymph node metastases, none more than
5 cm in greatest dimension
N
3
: Metastasis in lymph node more than 5 cm in
greatest dimension
M
1a
: Nonregional lymph node(s)
M
1b
: Bone(s)
M
1c
: Other site(s)
a
American Urologic System.
b
American Joint CommitteeInternational Union Against Cancer.
c
Tumor found in one or both lobes by needle biopsy but not palpable or visible by imaging is classied as T
1c
.
d
Invasion into the prostatic apex or into (but not beyond) the prostatic capsule is not classied as T
3
but as T
2
.
Chisholm_Ch89.qxd 6/13/07 05:57 PM Page 1363
1364 SECTION 16 / ONCOLOGIC DISORDERS
is diagnosed initially by PSA and DRE and conrmed by a
biopsy, where the Gleason score is assigned. Asymptomatic
patients with a low risk of recurrence, those with a T
1
or T
2
lesion with a Gleason score of 2 through 6 and a PSA of less than
10 ng/mL (10 mcg/L), may be managed by expectant manage-
ment or radiation
26
(Table 894). Since patients with asympto-
matic early-stage disease generally have an excellent 10-year
survival, immediate morbidities of treatment must be balanced
against the likelihood of dying from prostate cancer. In general,
more aggressive treatments of early-stage prostate cancer are
reserved for younger men, although patient preference is a
major consideration in all treatment decisions. In patients with
a normal life expectancy of equal to or greater than 10 years,
either observation, radiation (external beam or brachytherapy),
or radical prostatectomy may be offered. Radical prostatectomy
and radiation therapy generally are considered therapeutically
equivalent for localized prostate cancer, although neither has
been shown to be better than observation alone.
2628
Individuals with T
2b
and T
2c
disease or a Gleason score of 7
or a PSA ranging from 10 to 20 ng/mL (10 to 20 mcg/L) are
considered at intermediate risk for prostate cancer recurrence.
26
Individuals with less than a 10-year expected survival may be
offered expectant managment, radiation therapy, or radical
prostatectomy, and those with a greater than or equal to 10-year
life expectancy may be offered either radical prostatectomy or
radiation therapy (Table 895).
Patients at high risk of recurrence [stage T
3b
, a Gleason score
ranging from 8 to 10, or a PSA value greater than 20 ng/mL (20
mcg/L)] should be treated with androgen ablation for 2 to 3 years
combined with radiation therapy
26
(see Table 895). Selected
individuals with a low tumor volume may receive a radical
prostatectomy or radiation therapy.
29,30
Patients with T
3b
and T
4
disease have a very high risk of
recurrence and are not candidates for radical prostatectomy
because of extensive local spread of disease.
26
Androgen
ablation with an LHRH agonist plus an antiandrogen should be
used prior to radiation therapy for patients with locally advanced
prostate cancer to improve outcomes over radiation therapy alone.
Patients should be offered a combination of radiation therapy
and androgen ablation. Recent evidence suggests that androgen
ablation should be instituted at diagnosis rather than waiting
for symptomatic disease or progression to occur. In a random-
ized clinical trial enrolling 500 men with locally advanced
prostate cancer who were randomized to either immediate ini-
tiation of androgen ablation with either orchiectomy or andro-
gen ablation or deferred hormonal therapy, individuals with
immediate therapy had a median actuarial cause-specic sur-
vival duration of 7.5 years, whereas those with deferred treat-
ment had a median actuarial cause-specic survival duration of
5.8 years.
31
Androgen ablation therapy, with either orchiectomy, an
LHRH agonist alone, or an LHRH agonist plus an antiandrogen
(combined hormonal blockade), can be used to provide palliation
for patients with advanced (stage D
2
) prostate cancer. The effects
of androgen deprivation seem most pronounced in patients
with minimal disease at diagnosis.
26
Estrogens were once used
widely; however, the primary estrogen, diethylstilbestrol
(DES), was withdrawn from the United States market in 1997
owing to increased cardiovascular risk. Secondary hormonal
manipulations, cytotoxic chemotherapy, or supportive care is
used for the patient who progresses after initial therapy.
21
TABLE 894. Initial Management of Prostate Cancer with Low and Intermediate Recurrence Risk
Recurrence Risk Expected Survival Initial Therapy
Low Less than 10 years Expectant management or RT
T
12a
, Gleason 26, PSA Greater than or Expectant management or
less than 10 equal to 10 years RP with or without pelvic lymph
node dissection or RT
Intermediate Less than 10 years EM, RT or RP with or without pelvic
lymph node dissection
T
2b2c
, or Gleason 7, or Greater than or RP with or without pelvic lymph node
PSA 1020 equal to 10 years dissection or RT
EM = Expectant management; RT = Radiation therapy; RP = Radical prostatectomy; PSA = Prostate specic
antigen.
TABLE 895. Management of Prostate Cancer with High and
Very High Recurrence Risk
Recurrence Risk Initial Therapy
High
T
3a
, or Gleason 810, or PSA Androgen deprivation for 2 years
greater than 20 ng/mL and RT or RT or RP
Locally advanced
Very high RT + androgen deprivation
T
3b
T
4
or Androgen deprivation
Metastatic
Any T, N
1
Androgen deprivation or RT
Any T, any N, M
1
Androgen deprivation
Androgen ablation = serum testosterone levels less than 50 ng/mL.
LHRH agonist (medical castrations or surgical are equivalent).
RT = radiation therapy; RP = radical prostatectomy.
Chisholm_Ch89.qxd 6/13/07 05:57 PM Page 1364
CHAPTER 89 / PROSTATE CANCER 1365
Nonpharmacologic Therapy
Expectant Management
Expectant management, also known as observation or
watchful waiting, involves monitoring the course of disease
and initiating treatement if the cancer progresses or the
patient becomes symptomatic. A PSA determination and
DRE are performed every 6 months, with a repeat biopsy at
any sign of disease progression. The advantages of expectant
management are avoiding the adverse effects associated
with denitive therapies such as radiation and radical
prostatectomy and minimizing the risk of unnescessary
therapies. The major disadvantage of expectant manage-
ment is the risk that the cancer progresses and requires a
more intensive therapy.
26
Orchiectomy
Bilateral orchiectomy, or removal of the testes, rapidly
reduces circulating androgens to castrate levels (andro-
stenedione less than 50 ng/mL, 1.7 nmol/L).
15
However, many
patients are not surgical candidates owing to their advanced
age, and other patients nd this procedure psychologically
unacceptable.
15
Orchiectomy is the preferred initial treatment
in patients with impending spinal cord compression or ureteral
obstruction.
Radiation
The two commonly used methods for radiation therapy are
external-beam radiotherapy and brachytherapy.
26
In external-
beam radiotherapy, doses of 70 to 75 Gy are delivered in 35 to 41
fractions in patient with low-grade prostate cancer and 75 to 80
Gy for those with intermediate- or high-grade prostate cancer.
Brachytherapy involves the permanent implantation of radioac-
tive beads of 145 Gy of
125
I or 124 Gy of
103
Pd and generally is
reserved for individuals with low-risk cancers.
Radical Prostatectomy
Complications from radical prostatectomy include blood loss,
stricture formation, incontinence, lymphocele, stula forma-
tion, anesthetic risk, and impotence. Nerve-sparing radical
prostatectomy can be performed in many patients; 50% to 80%
regain sexual potency within the rst year. Acute complications
from radiation therapy include cystitis, proctitis, hematuria,
urinary retention, penoscrotal edema, and impotence (30% inci-
dence).
15
Chronic complications include proctitis, diarrhea, cys-
titis, enteritis, impotence, urethral stricture, and incontinence.
15
Since radiation and prostatectomy have signicant and immedi-
ate mortality when compared with observation alone, many
patients may elect to postpone therapy until symptoms
develop.
Pharmacologic Therapy
LHRH Agonists
Luteinizing hormonereleasing hormone (LHRH) agonists are
a reversible method of androgen ablation and are as effective as
orchiectomy in treating prostate cancer.
32
Currently available
LHRH agonists include leuprolide, leuprolide depot, leuprolide
implant, and goserelin acetate implant. Leuprolide acetate is
administered once daily, whereas leuprolide depot and gosere-
lin acetate implant can be administered either once monthly,
once every 12 weeks, or once every 16 weeks (leuprolide depot,
every 4 months). The leuprolide depot formulation contains
leuprolide acetate in coated pellets. The dose is administered
intramuscularly, and the coating dissolves at different rates to
allow sustained leuprolide levels throughout the dosing inter-
val. Goserelin acetate implant contains goserelin acetate dis-
persed in a plastic matrix of D,L-lactic and glycolic acid copoly-
mer and is administered subcutaneously. Hydrolysis of the
copolymer material provides continuous release of goserelin
over the dosing period. A recently approved leuprolide implant
is a mini-osmotic pump that delivers 120 mcg of leuprolide
daily for 12 months. After 12 months, the implant is removed,
and a different implant can be placed.
Several randomized trials have demonstrated that leuprolide
and goserelin are effective agents when used alone in patients
with advanced prostate cancer.
19
Response rates around 80%
have been reported, with a lower incidence of adverse effects
compared with estrogens.
19
There are no direct comparative tri-
als of the currently available LHRH agonists or the dosage for-
mulations, but a recent meta-analysis reported that there is no
difference in efcacy or toxicity between leuprolide and gosere-
lin. Therefore, the choice between the two usually is made based
on cost and patient and physician preference for a dosing
schedule.
The most common adverse effects reported with LHRH
agonist therapy include a disease are-up during the rst week
of therapy, hot ashes, erectile impotence, decreased libido, and
injection-site reactions.
19
The disease are-up is thought to be
caused by initial induction of LH and FSH by the LHRH ago-
nist and manifests clinically as either increased bone pain or
increased urinary symptoms.
19
This are reaction usually
resolves after 2 weeks and has a similar onset and duration pat-
tern for the depot LHRH products.
33,34
Patient Encounter 2
GG is a 72-year-old man with newly diagnosed prostate
cancer. He has no symptoms, and he was diagnosed on
routine screening. He is stage T
1
, his Gleason score is 2,
and his PSA is 6 ng/mL (6 mcg/L).
What treatment options are available to GG?
Chisholm_Ch89.qxd 6/13/07 05:57 PM Page 1365
1366 SECTION 16 / ONCOLOGIC DISORDERS
LHRH agonist monotherapy can be used as initial therapy,
with similar response rates to orchiectomy and estrogen admin-
istration expected. There is a lower incidence of cardiovascular-
related adverse effects associated with LHRH agonist therapy
than with estrogen administration. Patients should be counseled
to expect worsening symptoms during the rst week of therapy,
and caution should be exercised when initiating LHRH agonist
therapy in patients with widely metastatic disease involving the
spinal cord or having the potential for ureteral obstruction
because irreversible complications may occur.
Antiandrogens
Three antiandrogens, utamide, bicalutamide, and nilutamide,
are currently available (Table 896). Antiandrogens have been
used as monotherapy in previously untreated patients, but a
recent meta-analysis determined that monotherapy with antian-
drogens is less effective than LHRH agonist therapy.
34
Efcacy of
the antiandrogens was similar.
21,3537
Objective responses are
manifested as decreased bone pain, decreased prostate size,
decreased PSA, and/or improved performance status. However,
for advanced prostate cancer, all currently available anti-
androgens are indicated only in combination with androgen-
ablation therapy; utamide and bicalutamide are indicated in
combination with an LHRH agonist, and nilutamide is indi-
cated in combination with orchiectomy.
21
The most common
antiandrogen-related adverse effects are listed in Table 896.
Combined Hormonal Blockade
Although up to 80% of patients with advanced prostate cancer
will respond to initial hormonal manipulation, almost all
patients will relapse within 2 to 4 years of initiating therapy.
15
The rationale for combination hormonal therapy is to inter-
fere with multiple hormonal pathways to completely eliminate
androgen action. In clinical trials, combination hormonal
therapy, sometimes also referred to as maximal androgen dep-
rivation or total androgen blockade, has been used. The combi-
nation of LHRH agonists or orchiectomy and antiandrogens is
the most extensively studied combined androgen-deprivation
approach.
Combining an LHRH agonist with utamide demon-
strated response rates greater than 90% in previously
untreated patient, and the median survival was 61 months in
the combination arm and 41 months in the leuprolide-alone
arm in patients with minimal disease.
38
However, in a com-
parison of goserelin with goserelin and utamide conducted
in 589 patients with 10 years of follow-up, combined andro-
gen blockade (CAB) showed no benet over goserelin alone.
39
The most recent meta-analysis of 27 randomized trials in
8275 patients (4803 treated with utamide, 1683 treated with
nilutamide, and 1784 treated with cyproterone) comparing
maximal androgen blockade with conventional medical or
surgical castration showed a small survival benet at 5 years for
those treated with utamide or nilutamide (27.6%) compared
with those treated with castration alone (24.7%; p = 0.0005).
40
Although some investigators now consider CAB to be the
initial hormonal therapy of choice for newly diagnosed
patients, the clinician is left to weigh the costs of combined
therapy against potential benets in light of conicting results
in the randomized trials
21
and the modest benet seen in the
meta-analysis.
40
For trials that did show an advantage for CAB,
whether these effects are specic to the testosterone-deprivation
method (orchiectomy versus leuprolide versus goserelin), the
antiandrogen, the duration of therapy, or patient selection is
not clear. Until further carefully designed studies that use sur-
vival, time to progression, quality of life, patient preference,
and cost as end points are conducted, it is appropriate to use
either LHRH agonist monotherapy or CAB as initial therapy
TABLE 896. Antiandrogens
Antiandrogen Usual Dose Adverse Effects
Flutamide 750 mg/day Gynecomastia
Hot ushes
Gastrointestinal
disturbances (diarrhea)
Liver function test
abnormalities
Breast tenderness
Methemoglobinemia
Bicalutamide 50 mg/day Gynecomastia
Hot ushes
Gastrointestinal
disturbances (diarrhea)
Liver function test
abnormalities
Breast tenderness
Nilutamide 300 mg/day for Gynecomastia
rst month, then Hot ushes
150 mg/day Gastrointestinal
disturbances (nausea
or constipation)
Liver function test
abnormalities
Breast tenderness
Visual disturbances
(impaired dark
adaptation)
Alcohol intolerance
Interstitial pneumonitis
Patient Encounter
CC is a 69-year-old man who presents with metastatic
prostate cancer. His disease is metastatic to the bones, and
his primary symptom is bone pain.
What treatment options are available?
Develop a treatment plan including medication and a
monitoring plan for both efcacy and toxicity.
Chisholm_Ch89.qxd 6/13/07 05:57 PM Page 1366
CHAPTER 89 / PROSTATE CANCER 1367
for metastatic prostate cancer. CAB may be most benecial for
improving survival in patients with minimal disease and for
preventing tumor are, particularly in those with advanced
metastatic disease. All other patients may be started on LHRH
agonist monotherapy, and an antiandrogen may be added after
several months if androgen ablation is incomplete.
Estrogens
DES was once a mainstay of prostate cancer therapy. While
very effective in androgen ablation, DES-treated patients expe-
rienced increased cardiovascular mortality.
41
LHRH agonists,
with equivalent efcacy and decreased cardiovascular toxicity,
supplanted DES as a mainstay of therapy.
Second-Line Therapy
Secondary or salvage therapies for patients who progress
after their initial therapy depend on what was used for initial
management.
26
For patients diagnosed initially with localized
prostate cancer, radiotherapy can be used in the case of failed
radical prostatectomy. Alternatively, androgen ablation can be
used in patients who progress after either radiation therapy or
radical prostatectomy.
Secondary hormonal manipulations, such as adding an antian-
drogen to a patient who incompletely suppresses testosterone secre-
tion with an LHRH agonist, or withdrawing antiandrogens in a
patient receiving combination therapy, or using agents that inhibit
androgen synthesis, can be attempted in patients treated initially
with one hormonal modality. Supportive care, chemotherapy, or
local radiotherapy can be used in patients who have failed all forms
of androgen-ablation manipulations because these patients are
considered to have androgen-independent disease.
For patients who initially received an LHRH agonist alone,
castration testosterone levels should be documented. Patients
with inadequate total testosterone suppression (greater than
20 ng/dL, or 0.694 nmol/L) can be treated by adding an anti-
androgen or performing an orchiectomy. If castration testo-
sterone levels have been achieved, the patient is considered to
have androgen-independent disease, and palliative androgen-
independent salvage therapy can be used.
Antiandrogen withdrawal, for patients having progressive
disease while receiving combined hormonal blockade with an
LHRH agonist plus an antiandrogen, can provide additional
symptomatic relief. Mutations in the androgen receptor have
been documented that cause antiandrogen compounds to act like
receptor agonists.
If the patient initially received combined androgen block-
ade with an LHRH agonist with an antiandrogen, then andro-
gen withdrawal is the rst salvage manipulation.
42
Objective
and subjective responses have been noted following the dis-
continuation of utamide, bicalutamide, or nilutamide in
patients receiving these agents as part of combined androgen
ablation with an LHRH agonist. Mutations in the androgen
receptor have been demonstrated that allow antiandrogens
such as utamide, bicalutamide, and nilutamide (or their
metabolites) to become agonists and activate the androgen
receptor. Patient responses to androgen withdrawal manifest
as signicant PSA reductions and improved clinical symp-
toms. Androgen withdrawal responses lasting 3 to 14 months
have been noted in up to 35% of patients, and predicting
response seems to be related most closely to longer androgen
exposure times.
42
Incomplete cross-resistance has been noted
in some patients who received bicalutamide after they had
progressed while receiving utamide.
35
Adding an agent that
blocks adrenal androgen synthesis, such as aminoglutethimide,
at the time that androgens are withdrawn may produce a
better response than androgen withdrawal alone. Because of
the potential for response immediately after antiandrogen
withdrawal, a sufcient observation and assessment period
(usually 46 weeks) is required before a patient can be enrolled
on a clinical trial evaluating a new agent or therapy for advanced
prostate cancer.
Androgen synthesis inhibitors, such as aminoglutethimide
and ketoconazole, can provide symptomatic relief for a short
time in approximately 50% of patients with progressive
disease despite previous androgen-ablation therapy.
21
Adverse
effects during aminoglutethimide therapy occur in approxi-
mately 50% of patients.
21
Central nervous system effects that
include lethargy, ataxia, and dizziness are the major adverse
reactions. A generalized morbilliform, pruritic rash has been
reported in up to 30% of patients treated. The rash is usually
self-limiting and resolves within 5 to 8 days with continued
therapy. Adverse effects from ketoconazole include gastroin-
testinal intolerance, transient rises in liver and renal function
tests, and hypoadrenalism.
After all hormonal manipulations are exhausted, the patient
is considered to have androgen-independent disease, and
chemotherapy or palliative supportive therapy is appropriate.
26
Palliation can be achieved by pain management, using
radioisotopes for bone-related pain, analgesics, cortico-
steroids, bisphosphonates,
43
and local radiotherapy.
26
Data are
emerging that demonstrate that bisphosphonates such as
pamidronate and zoledronic acid may prevent skeletal mor-
bidity, such as pathologic fractures and spinal cord com-
pression, in men with hormone-refractory prostate cancer;
however, other studies have shown no benet. The early use
of bisphosphonates also has been shown to prevent bone
loss owing to androgen deprivation therapy. The usual dose
of pamidronate is 90 mg every month, and the usual dose of
zoledronic acid is 4 mg every 3 to 4 weeks. A trial of pamidronate
or zoledronic acid can be initiated in prostate cancer patients
with bone pain; if no benet is observed, the drug may be
discontinued.
44
Chemotherapy, with docetaxel and prednisone or docetaxel
and estramustine, improves survival in patients with hormone-
refractory prostate cancer. Patients with hormone-refractory
prostate cancer also may be considered for entry into clinical
Chisholm_Ch89.qxd 6/13/07 05:57 PM Page 1367
1368 SECTION 16 / ONCOLOGIC DISORDERS
trials investigating new therapies for prostate cancer.
Docetaxel 75 mg/m
2
every 3 weeks and prednisone 5 mg twice
a day improve survival in hormone-refractory metastatic
prostate cancer.
45,46
(Table 897). The most common adverse
events reported with this regimen are nausea, alopecia, and
bone marrow suppression. In addition, uid retention and
peripheral neuropathy, known effects of docetaxel, are
observed. The combination of estramustine (280 mg three
times a day on days 15) and docetaxel 60 mg/m
2
on day 2 every
3 weeks also improves survival in hormone refractory
metastatic prostate cancer. Estramustine causes a decrease in
testosterone and a corresponding increase in estrogen; there-
fore, the adverse effects of estramustine include an increase in
thromboembolic events and gynecomastia and decreased
libido. Estramustine is an oral capsule and should be
refridgerated. Calcium inhibits the absorption or estramus-
tine, so concurrent administration should be avoided. While
both the docetaxel-prednisone and the docetaxel-estramustine
regimens are effective in hormone-refractory prostate cancer,
most clinicians prefer the docetaxel-prednisone regimen
because of the cardiovascular adverse effects associated with
estramustine. In addition, androgen ablation usually is contin-
ued when chemotherapy is initiated.
26
OUTCOME EVALUATION
Monitoring of prostate cancer depends on the stage of the
cancer.
26
When denitive, curative therapy is attempted,
objective parameters to assess tumor response include assess-
ment of the primary tumor size, evaluation of involved
lymph nodes, and the response of tumor markers such as PSA
to treatment. Following denitive therapy, the PSA level is
checked every 6 months for the rst 5 years and then annually.
Local recurrence in the absence of a rising PSA may occur,
so DRE is also performed. In the metastatic setting, clinical-
benet responses can be documented by evaluating per-
formance status changes, weight changes, quality of life, and
analgesic requirements, in addition to the PSA or DRE at 3-
month intervals.
ABBREVIATIONS
ACS: American Cancer Society
AUS: American Urologic System
BPH: benign prostatic hyperplasia
CAB: combined androgen blockade
DES: diethylstilbestrol
DHT: dihydrotestosterone
DRE: digital rectal examination
EGF: epidermal growth factor
FSH: follicle-stimulating hormone
IGF: insulin-like growth factor
LH: luteinizing hormone
LHRH: luteinizing hormonereleasing hormone
TABLE 897. First-Line Chemotherapy Regimens for Metastatic Hormone-Independent
Prostate Cancer
Regimen Usual Dose Adverse Effects Dose Adjustments
Docetaxel 75 mg/m
2
Fluid retention, Hepatic
q3-weeks alopecia, mucositis, AST/ALT greater than 1.5 times
myelosuppression, the upper limit of normal and
hypersensitivity alkaline phosphatase greater
than 2.5 upper limit of
normal, do not administer
Hematologic
Ensure complete blood count
recovered
Patient Care and Monitoring
1. Men, starting at age 40, should be offered a baseline PSA
determination and DRE, with annual screening offered
starting at age 50.
2. There are no currently recommended prostate cancer
chemoprevention agents.
3. The diagnosis of prostate cancer is made by biopsy.
4. Prostate cancer treatment depends on the stage, age,
Gleason score, and PSA concentration. Treatment options
include expectant management, radiation therapy, radi-
cal prostatectomy, hormonal therapy, and chemotherapy.
5. While receiving treatment for prostate cancer, patients
should be monitored for efcacy and toxicity.
6. Measures of efcacy include disappearance of tumor or
decrease in tumor, resolution of symptoms, or a decline
in the PSA.
7. Measures of toxicity vary by the treatment; work with
patients to ensure that they understand the expected toxi-
cities of their regimen and that they should report them.
8. Counsel patients to be compliant with all treatment regi-
mens and appointments.
Chisholm_Ch89.qxd 6/13/07 05:57 PM Page 1368
CHAPTER 89 / PROSTATE CANCER 1369
NCCN: National Comprehensive Cancer Network
NCI: National Cancer Institute
PCPT: Prostate Cancer Prevention Trial
PSA: prostate-specic antigen
TRUS: transrectal ultrasound
VACURG: Veterans Administration Cooperative Urologic Research
Group
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Log into the website: www.pharmacotherapyprinciples.com
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