Prostate Cancer Final Presentation 2003

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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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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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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T2:The tumor can be felt during a DRE and the cancer

is confined within the prostate gland.


T2a

T2b

T2c


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T3:the tumor has extended through the prostatic

capsule or to the seminal vesicles, but no other

organs are affected.


T3a

T3b

T3c


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T4:The tumor has spread or attached to tissues next

to the prostate (other than the seminal vesicles).


T4a

T4b


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N Stages:


N0N1

N2

N3

Lymph node involvement


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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!

Documents

Prostate Cancer Final Presentation 2003