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Prostate Cancer

Epidemiology

Most common cancer diagnosis

Second leading cause of cancer death in men

In 2000, 180,400 cases were diagnosed and 31,900 men died

Risk factors

Age

Rare under the age of 40

Median incidence in men >50 years old

Race-ethnicity

United States report the highest incidents

Japan and other Asian countries the disease is rare

African-American have the highest rate in the world

Family history

1 + family history is associated with 2-3 fold risk elevation

Diet

High fat doubles the risk

Retinol, vitamin A increases the risk

Decrease intake of vit.D, vit.E, and B-carotene increases risk

Risk factor (Cont.)

Occupational exposure

Alkaline batteries come into contact with cadmium, a trace mineral that may be antagonistic to zinc. Zinc is found in very high levels in the prostate and is required in several enzymes involved in DNA and RNA repair and synthesis.

Hormonal

Testosterone, commonly implicated in the pathogenesis of prostate cancer, is 15% higher in African-American men when compared to Caucasian males.

5-a -reductase, the enzyme that converts testosterone to its more active form, dihydrotestosterone, in the prostate, is decreased in Japanese men compared to African-American and Caucasians

Benign prostatic hyperplasia

Vasectomy

Pathology

Mutation of genes, thought to be begin at stage B-D

P53

Lost of function may result in replication of damaged DNA and subsequently unregulated cell growth

Mutation thought to be caused by environmental toxins.

KAI1, (Chinese) antimetastatic gene

mutate

Androgen receptor gene

Altering the hormone binding activity

Mutated not only by testicular androgens but also by several androgens, steroids, and nonsteroidal antiandrogens

Clinical presentation

Localize disease

Urinary frequency

Hesitancy

Dribbling

impotence

Metastases

Back pain

Stiffness

Osseous metastases

Spinal cord lesion

If not properly treated

Exams

Digital rectal examination

Since 1900s for the detection of prostate cancer

>85% specific

Prostate-specific antigen

A prostate specific glycoprotein produced only in the cytoplasm of benign and malignant prostate cells.

Limitation: low specificity

Inc in acute urinary retention, acute prostatitis, benign prostatic hyperoplasia

Diagnostic and staging workup

Initial tests

DRE

PSA

Transrectal ultrasonagrahy if either DRE or PSA +

Staging tests

Bone scan

CBC

LFT

Chest X-ray

Gleason score of biopsy specimen

Additional staging exam

Lymph node evaluation

Pelvic CT scan

Transrectal MRI

Screening recommendations

The American cancer society (ACS) currently recommends that DRE and PSA be offered annually to men beginning at age 50 with at least a 10 year life expectancy and to younger men (45) who are considered to be at high risk for prostate cancer

The ACS define abnormal PSA value to be above 4.0 ng/ml.

If both test are normal, no further diagnostic action is required

However, if either is abnormal, further workup by transrectal ultrasonography is indicated

Staging

The American Urologic System (AUS) is the most commonly used staging system in the United States

Patients are assign to stage A-D

Corresponding to subcategories based on size of the tumor, local or regional extension, presence of involved lymph node groups, and presence of metastases

Prognosis

Depend on histological grade, the tumor size, and local extent of the primary tumor.

Histological grade is important

Degree of differentiation ultimately determines the stage of disease

DNA content

Cell proliferate activity

Epidermal growth factor

P53 tumor suppressor gene

10 year cancer-specific survival

Treatment

General approach to treatment

Orchiectomy

Luteinizing hormone-releasing hormone agonists (LH-RH) Agonist

Antiandrogens

Estrogens

Chemoprevention

Desired outcome

Localized prostate disease: Is curable by surgery radiation

Reduce any post procedure complications

Impotence

Stricture

incontinence

Advanced prostate disease: Not curable

Providing symptom relief

Maintaining quality of life

Orchiectomy

Surgical removal of testis

Bilateral orchiectomy rapidly reduces circulating androgens to castrate level (<50ng/dl)

Probably the preferred initial treatment in patients with spinal cord compression or ureteral obstruction

Many patients are not candidate

Advanced age

Psychologically unacceptable

LH-RH agonist

Leuprolide, Leuprolide depot, Gaserelin acetate implant

Response rate about 80%

No data comparing among LH-RH agonist

SE: "flare up" during the first week of therapy, hot flashes, impotence, decreased libido, injection site reaction. Usually result after 2 weeks

Antiandrogens

Response rate %

Flutamide 50-87

Bicalutamide 54-70

Nilutamide 40

Objective response are as dec. bone pain, prostate size, PSA, improved performance status.

Advance prostate cancer

Indicated only in combination with androgen-ablation therapy

Flutamide and bicalutamide: combination with LH—RH agonist

Nilutamide : combination with orchiectomy

Antiandrogens

Chemotherapy

Mitoxantrone + Corticosteroids (Prednisone)

Estramustine + Vinblastine

Provide clinical benefit response in patients with hormone refractory prostate cancer