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8/6/2019 Prostate Cancer Final Presentation 2003
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PROSTATE CANCER
BY,
Natik-Bi-Illah
He died yesterday. In October 2009 that
he had been diagnosed with prostate
cancer
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NORMAL PROSTATE GLAND
The prostate gland is a walnut-sized muscular organ,which is located in front of rectum and is situatedjust below the bladder in male.
Since, the gland surrounds urethra and is belowurinary bladder, it can be felt in course of a rectalexam.
Proper functioning of the male prostate gland isdependent on male hormones like testosterone.
The prostate gland starts growing during puberty inmales and keeps growing throughout the life, thoughits rate of growth slows down after 25 years of age.
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FUNCTIONS OF PROSTATE GLAND :
Aids sperm motility and survival
Helps propel semen fluid
Controls and prevents urine entry duringejaculation
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PATHOLOGY
There are two main types of epithelial cell in theprostate gland: a single layer of flattened basal cells & asingle layer of secretory columnar luminal cells.
During the development of prostate cancer, the normalprostate structure is altered.
The main changes result in a breakdown of the basalcell barrier between the prostatic duct and thesurrounding stroma.
These breakdowns lead to invasion of luminal cells intothe surrounding stroma, which can eventually lead tomigration of these cells into the rest of the body.
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The piling up of luminal cells in the prostate iscalled prostatic intraepithelial neoplasia (PIN).
PIN is segregated into low grade and high grade.
The normal luminal cells are very similar to one
another in size, shape, and the location of thenucleus (the round circle within the cells) towardthe basal layer.
In low-grade PIN the luminal cells become less
uniform; the nuclei are no longer located solelyat the basal layer, becoming enlarged andcontaining enlarged dark spots referred to asnucleoli. The cells appear to be piled on top ofeach other.
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In high-grade PIN these characteristics
become more pronounced, the nuclei
become very large and the nucleoli are veryprominent, and the basal layer begins to
have small gaps. In early prostate cancer
(carcinoma), there is an additional loss ofthe complete basal layer.
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DIAGNOSIS OF PROSTATE CANCER
DIGITAL RECTAL EXAMINATION
To perform a DRE, the doctor
uses a gloved index or middle
finger to feel the prostate throughthe rectal wall. With little effort,
an experienced physician can
determine the size and hardness
of the prostate. Normally it is soft
and pliable but a hard nodule iscause for suspicion of prostate
cancer and requires further
testing.
DRE
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DIAGNOSIS OF PROSTATE CANCER
PSA was discovered in the late 1960s and was first used in forensic analysis to test for
semen at crime scenes. In fact a simple blood test can be used to measure accurate
levels of PSA.
PSA
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DIAGNOSIS OF PROSTATE CANCER
TRANSRECTAL
ULTRASOUND-
GUIDED
PROSTATE
NEEDLE BIOPSY
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EPIDEMIOLOGY
Figure: Prostate cancer incidence worldwide, Globocan 2002 (Ferley et al. 2004)
Incidence:
In 2002 - 679,000 men
developed prostate cancer
worldwide
Mortality:
In 2002- 221,000 deaths
worldwide
Prevalence:
in 2002 was
2,368,700 cases
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ETIOLOGY
Prostatecancer
Racial/EthnicVariation
Hormonesand Growth
Factors
GeneticFactors
Occupation
PhysicalActivity
Obesity
Diet``
Age
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MORPHOLOGY
Adenocarcinoma of the
prostate. Carcinomatoustissue is seen on the posterior
aspect (lower left). Note the
solid whiter tissue of cancer
in contrast to the spongyappearance of the benign
peripheral zone on the
contralateral side.
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MORPHOLOGY
Difference between histology of Normal and cancer prostate
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HISTOLOGIC GRADE
Gleason Grading
System.As prostate
cancerbecomes more
aggressive, the glands
become less
organized, with
smaller and more
variable lumen sizes.
Highly aggressive
cancercan have
obvious lumens.Each
panel from top to
bottom representsan
increasing Gleason
grade.
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STAGING BY TNM SYSTEM
TStages
:
T1:
the tumor can not be felt during a digital rectal exam, or
seen by imaging studies, but cancer cells are found in a
biopsy specimen.
The T1 stages included:
T1a
T1bT1c
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STAGING BY TNM SYSTEM
T2:The tumor can be felt during a DRE and the cancer
is confined within the prostate gland.
The T2 stages included:
T2a
T2b
T2c
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STAGING BY TNM SYSTEM
T3:the tumor has extended through the prostatic
capsule or to the seminal vesicles, but no other
organs are affected.
The T3 stages included:
T3a
T3b
T3c
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STAGING BY TNM SYSTEM
T4:The tumor has spread or attached to tissues next
to the prostate (other than the seminal vesicles).
The T4 stages included:
T4a
T4b
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STAGING BY TNM SYSTEM
N Stages:
The T4 stages included:
N0N1
N2
N3
Lymph node involvement
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STAGING BY TNM SYSTEM
M Stages:
The M stages included:
M0
M1
Metastasis to distant sites
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THERAPEUTIC STRATEGIES
There are two types of prostate cancer when it
comes to treatment:
organ-confined prostate cancer
Advance prostate cancer
There are numerous treatment options with
regard to the potentially optimal managementof prostate cancer.
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NON-PHARMACOLOGICALTHERAPIES
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EXPECTANT MANAGEMENT
watchful waiting,involves monitoring thecourse of disease andinitiating treatment if
the cancer progressesor the patient becomessymptomatic.
A PSA determination
and DRE are performedevery 6 months, with arepeat biopsy at anysign of diseaseprogression.
The advantages :
avoiding the adverse effects
associated with definitive therapies
such as radiation and radical
prostatectomy and minimizing the
risk of unnecessary therapies.
disadvantage:
the risk that the cancer progresses
and requires a more intensivetherapy.
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SURGERY
Surgical treatment of prostate cancer has seen
many improvements in the past two decades,
including laparoscopy, robotic surgery, and
better assessment of quality of life and
functional results.
Patients with clinically organ-confined prostate
cancer are the best candidates for radicalprostatectomy.
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RADICAL PROSTATECTOMY
Radical prostatectomy consists of removing the
whole prostate gland and the seminal vesicles.
Two approaches can be used:
the retropubic approach,
the perineal approach,
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RADICAL PROSTATECTOMY
Retropubic approach
This is a surgical procedure to remove
the prostate through an incision in the
abdominal wall. Removal of nearby
lymph nodes may be done at the
same time.
Perineal prostatectomy
This is a surgical procedure to
remove the prostate through an
incision made in the perineum.
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RADIATION THERAPY
This type of treatments involves the uses high-
energy x-rays or other types of radiation to kill
cancer cells or keep them from growing.
The two commonly used methods for radiation
therapy are:
External-beam radiotherapy
Brachytherapy
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EXTERNAL-BEAM RADIOTHERAPY:
There a computer-operatedmachine is used to focus abeam of radiation on theprostate.
doses of 70 to 75 Gy aredelivered in patient with low-grade prostate cancer and75 to 80 Gy for those withintermediate- or high-gradeprostate cancer are given in
externalbeam radiotherapy.
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BRACHYTHERAPY.
Brachytherapyinvolves thepermanent
implantation ofSlow-releaseradioactive pelletsare implanted into
the prostate usingan ultrasoundguided needle.
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PHARMACOLOGIC THERAPY
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HORMONAL THERAPY AND ITS
SIGNIFICANCE
The effect of androgen andits function in the prostategland have been studied.the growth of prostaticneoplasms is generally
dependent on androgens.
hormone manipulation inpatients with metastaticprostate cancer (PCa),hormonal therapy remains
major therapeutic optionfor advanced disease.
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DIETHYLSTILBESTROL (DES)
In the 1940s, the firstreversible androgen ablationmethod was achieved by
administration of DES, a semi-synthetic estrogen compound.
DES was once a main mode of prostate cancer
therapy. LHRH agonists, with equivalent
efficacy and decreased cardiovascular toxicity,
replaced DES.
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LH-RH AGONISTS
Luteinizing hormonereleasing hormone
(LHRH) agonists are a reversible method of
androgen ablation and are as effective as
orchiectomy in treating prostate cancer.
Currently available LHRH agonists include:
leuprolide, and goserelin
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LH-RH AGONISTS
Mechanism of action: LH-RH is generally secreted by the hypothalamus inpulses, leading to pulsatile secretion ofLH by the pituitary. This in turnpromotes testosterone secretion by the Leydig cells of the testes. However,constantly high levels ofLH-RH that occur with agonist administration down-regulate the receptors in the pituitary, inhibit LH secretion, and therebyreduce testosterone production. In addition, some studies have suggested a
direct inhibitory effect ofLH-RH via LH-RH receptors in PCa cells. Dose:
Leuprolide acetate is administered once 1 mg per day intramuscularly
leuprolide depot and goserelin acetate implant can be administered either oncemonthly, once every 12 weeks, or once every 16 weeks (leuprolide depot, every4 months): Intramuscular, 7.5 mg once a month , 22.5 mg once every threemonths (12 weeks), or 30 mg every four months.
Goserelin inject 3.6 mg by subcutaneous route every 28 days or inject 10.8 mgby subcutaneous route every 12 weeks
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LH-RH AGONISTS
Adverse effect:
The most common adverse effects reported with LHRH agonisttherapy include: a disease flare-up during the first week of therapy
hot flashes erectile impotence
decreased libido
and injection-site reactions
The disease flare-up is thought to be caused by initial inductionofLH and FSH by the LHRH agonist and manifests clinicallyas either increased bone pain or increased urinarysymptoms. It subsides after a few weeks.
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ANTIANDROGEN MONOTHERAPYAntiandrogen Usual Dose Adverse Effects Structure
Flutamide 750 mg/day Gynecomastia
Hot flushes
Gastrointestinal
disturbances (diarrhea)
Liver function test
abnormalities
Breast tenderness
Methemoglobinemia
Bicalutamide 50 mg/day Gynecomastia
Hot flushes
Gastrointestinal
disturbances (diarrhea)
Liver function test
abnormalities
Breast tenderness
Gynecomastia
Nilutamide 300 mg/day for first month,
then 150 mg/day
Gastrointestinal
disturbances (nausea or constipation)
Liver function test
abnormalities
Breast tenderness
Visual disturbances (impaired dark
adaptation)
Alcohol intolerance
Interstitial pneumonitis
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MECAHNISM OF ACTION OF ANTI
ANDORGEN
These compounds interfere with the binding of
androgens to the AR in the target cell(e.g.
prostate cells), which prevents the activation of
AR pathways in those cells. Blockade of
androgens receptors by antiandrogens will
eliminate the negative feedback loop of
testosterone on the release of luteinizinghormone (LH).
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COMBINED ANDROGEN BLOCKADE
The basis of combine androgen blocking is
blocking all the sources of androgens. CAB
consists of treatment with a LH-RH agonist or
surgical castration along with a non-steroidal
antiandrogen.
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CHEMOTHERAPY:
Chemotherapy should reserved for hormonerefractory prostate cancer.When the disease has reached state where it demonstrates progressiondespite low levels of testosterone after castration or other therapeuticmeasures is called hormonerefractory prostatecancer.
Chemotherapy, with docetaxel and prednisone or docetaxel andestramustine, improves survival in patients with hormonerefractory prostatecancer.
Docetaxel 75mg/m2 every 3 weeks and prednisone 5 mg twice a day improvesurvival in hormone-refractory metastatic prostate cancer.
The most common adverse events reported with this regimen are nausea,alopecia, and bone marrow suppression. In addition, fluid retention andperipheral neuropathy, known effects of docetaxel, are observed.
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PREVENTION STRATEGIES
1. Eat a well-balanced diet rich in fruits and vegetables. Strivefor at least five servings of fruits and vegetables a day. Lookfor alternatives rich in lycopene, such as tomato-basedsauces, grapefruit, and watermelon. Increase the amount ofcruciferous vegetables.
2. Reduce intake of fat and particularly fat from red meat.Substitute two to three servings of fish a week for red meat.Cook with canola or olive oil.
3. Add soy-based foods to your diet.
4. Supplement your diet with at least 1000 IU of vitamin D3 perday, but do not exceed 2000 IU per day.
5. Avoid or minimize exposure to carcinogens (cadmium andpesticides) and reduce the amount of grilled meat.
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THANK YOU!