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He died yesterday.

In October 2009 that he had been diagnosed with prostate cancer

BY, Natik-Bi-Illah

PROSTATE CANCER

NORMAL PROSTATE GLAND

The prostate gland is a walnut-sized muscular organ, which is located in front of rectum and is situated just below the bladder in male. Since, the gland surrounds urethra and is below urinary bladder, it can be felt in course of a rectal exam. Proper functioning of the male prostate gland is dependent on male hormones like testosterone. The prostate gland starts growing during puberty in males and keeps growing throughout the life, though its rate of growth slows down after 25 years of age.

FUNCTIONS OF PROSTATE GLAND :

Aids sperm motility and survival Helps propel semen fluid Controls and prevents urine entry during ejaculation

PATHOLOGY

There are two main types of epithelial cell in the prostate gland: a single layer of flattened basal cells & a single layer of secretory columnar luminal cells. During the development of prostate cancer, the normal prostate structure is altered. The main changes result in a breakdown of the basal cell barrier between the prostatic duct and the surrounding stroma. These breakdowns lead to invasion of luminal cells into the surrounding stroma, which can eventually lead to migration of these cells into the rest of the body.

The piling up of luminal cells in the prostate is called 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 the nucleus (the round circle within the cells) toward the basal layer. In low-grade PIN the luminal cells become less uniform; the nuclei are no longer located solely at the basal layer, becoming enlarged and containing enlarged dark spots referred to as nucleoli. The cells appear to be piled on top of each other.

In high-grade PIN these characteristics become more pronounced, the nuclei become very large and the nucleoli are very prominent, and the basal layer begins to have small gaps. In early prostate cancer (carcinoma), there is an additional loss of the complete basal layer.

DIAGNOSIS OF PROSTATE CANCER

DRE

DIGITAL RECTAL EXAMINATION To perform a DRE, the doctor uses a gloved index or middle finger to feel the prostate through the 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 is cause for suspicion of prostate cancer and requires further testing.

DIAGNOSIS OF PROSTATE CANCER

PSA

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.

DIAGNOSIS OF PROSTATE CANCER

TRANSRECTAL ULTRASOUNDGUIDED PROSTATE NEEDLE BIOPSY

EPIDEMIOLOGY
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


Figure: Prostate cancer incidence worldwide, Globocan 2002 (Ferley et al. 2004)

ETIOLOGY
Racial/Ethnic Variation Hormones and Growth Factors

Age

Diet``

Prostate cancer

Genetic Factors

Obesity

Occupation

Physical Activity

SYMPTOMS AND CLINICAL MANIFESTATION


            

Urination becomes more difficult & blocks the flow of urine Difficulty in starting or stopping the urine flow Burning with urination Blood in the urine Enlargement of urinary bladder Blood in the semen Erectile dysfunction Painful ejaculation Bone pain (especially in the lower back, hips, or ribs) Discomfort in the pelvic area pain in the abdomen Jaundice Lung metastases can cause chest pain and coughing.

MORPHOLOGY

Adenocarcinoma of the prostate. Carcinomatous tissue is seen on the posterior aspect (lower left). Note the solid whiter tissue of cancer in contrast to the spongy appearance of the benign peripheral zone on the contralateral side.

MORPHOLOGY
Difference between histology of Normal and cancer prostate

HISTOLOGIC GRADE
Gleason Grading System. As prostate cancer becomes more aggressive, the glands become less organized, with smaller and more variable lumen sizes. Highly aggressive cancer can have obvious lumens. Each panel from top to bottom represents an increasing Gleason grade.

STAGING BY TNM SYSTEM


T Stages:

 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  T1b  T1c

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

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

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

STAGING BY TNM SYSTEM


N Stages:

The T4 stages included:

 N0  N1  N2  N3
Lymph node involvement

STAGING BY TNM SYSTEM


M Stages:

The M stages included:

 M0  M1

Metastasis to distant sites

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 management of prostate cancer.

NON-PHARMACOLOGICAL THERAPIES

EXPECTANT MANAGEMENT

watchful waiting, involves monitoring the course of disease and initiating treatment 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 : 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 intensive therapy.

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 radical prostatectomy.

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,

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.

ADVANTAGE AND DISADVANTAGE OF SURGERY


Advantage organ-confined prostate cancer completely eliminate the cancer from the body. PSA in the blood should go to zero. If PSA is still present after surgery, or if it begins to come back some time later, this is a helpful indication that the prostate cancer has metastasized. disadvantage potential for significant blood loss

men with heart disease are generally not good candidates

In addition, men who have fewer than 10 years of life expectancy may not be good candidates

erectile dysfunction incontinence

bowel injury

RADIATION THERAPY
This type of treatments involves the uses highenergy 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 Brachytherapy

radiotherapy

EXTERNAL-BEAM RADIOTHERAPY:

There a computer-operated machine is used to focus a beam of radiation on the prostate. doses of 70 to 75 Gy are delivered in patient with lowgrade prostate cancer and 75 to 80 Gy for those with intermediate- or high-grade prostate cancer are given in externalbeam radiotherapy.

BRACHYTHERAPY.

Brachytherapy involves the permanent implantation of Slow-release radioactive pellets are implanted into the prostate using an ultrasound guided needle.

PHARMACOLOGIC THERAPY

HORMONAL THERAPY AND ITS SIGNIFICANCE


The effect of androgen and its function in the prostate gland have been studied. the growth of prostatic neoplasms is generally dependent on androgens. hormone manipulation in patients with metastatic prostate cancer (PCa), hormonal therapy remains major therapeutic option for advanced disease.

DIETHYLSTILBESTROL (DES)

In the 1940s, the first reversible androgen ablation method was achieved by administration of DES, a semisynthetic estrogen compound.

DES was once a main mode of prostate cancer therapy. LHRH agonists, with equivalent efficacy and decreased cardiovascular toxicity, replaced DES.

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

LH-RH AGONISTS

Mechanism of action: LH-RH is generally secreted by the hypothalamus in pulses, leading to pulsatile secretion of LH by the pituitary. This in turn promotes testosterone secretion by the Leydig cells of the testes. However, constantly high levels of LH-RH that occur with agonist administration downregulate the receptors in the pituitary, inhibit LH secretion, and thereby reduce testosterone production. In addition, some studies have suggested a direct inhibitory effect of LH-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 once monthly, once every 12 weeks, or once every 16 weeks (leuprolide depot, every 4 months): Intramuscular, 7.5 mg once a month , 22.5 mg once every three months (12 weeks), or 30 mg every four months. Goserelin inject 3.6 mg by subcutaneous route every 28 days or inject 10.8 mg by subcutaneous route every 12 weeks

LH-RH AGONISTS
Adverse effect: The most common adverse effects reported with LHRH agonist therapy 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 induction of LH and FSH by the LHRH agonist and manifests clinically as either increased bone pain or increased urinary symptoms. It subsides after a few weeks.

LH-RH ANTAGONISTS

LH-RH receptor antagonists recently have been developed for androgen deprivation. Abarelix, the first peptide antagonist, directly blocks the binding of LH-RH to its receptor without agonist activity. However it is still under study.

ANTIANDROGEN MONOTHERAPY
Antiandrogen Flutamide Usual Dose 750 mg/day Adverse Effects 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) Structure

Liver function test abnormalities Breast tenderness Visual disturbances (impaired dark adaptation)

Alcohol intolerance Interstitial pneumonitis

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 luteinizing hormone (LH).

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.

CHEMOTHERAPY:
Chemotherapy should reserved for hormonerefractory prostate cancer. When the disease has reached state where it demonstrates progression despite low levels of testosterone after castration or other therapeutic measures is called hormonerefractory prostatecancer. Chemotherapy, with docetaxel and prednisone or docetaxel and estramustine, improves survival in patients with hormonerefractory prostate cancer. Docetaxel 75mg/m2 every 3 weeks and prednisone 5 mg twice a day improve survival 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 and peripheral neuropathy, known effects of docetaxel, are observed.

PREVENTION STRATEGIES
1. Eat a well-balanced diet rich in fruits and vegetables. Strive for at least five servings of fruits and vegetables a day. Look for alternatives rich in lycopene, such as tomato-based sauces, grapefruit, and watermelon. Increase the amount of cruciferous 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 per day, but do not exceed 2000 IU per day. 5. Avoid or minimize exposure to carcinogens (cadmium and pesticides) and reduce the amount of grilled meat.

THANK YOU!