Carcinoma of prostateCarcinoma of prostate

Prepared byPrepared by

Dr. sarwar N mahmoodDr. sarwar N mahmood

F.I.C.M.S( urology),F.E.B.U, E.A.UF.I.C.M.S( urology),F.E.B.U, E.A.U

Carcinoma of prostateCarcinoma of prostate

• CaP is the most common cancer diagnosed and is the second leading cause of cancer death in American men, and the prevalence of CaP increases with age.

• 60-70% of CaP originates in the peripheral zone, 10-20% in the transitional zone, 5-10 % in the central zone.

Risk factorsRisk factors• Increasing age: probability of CaP developing in men under the age

of 40 is 1 in 10000.and for men 60-79 it is 1 in 8.

• Race: African American are at higher risk for CaP than whites. And tumor tends to be more aggressive than in white race also.

• Positive family history increase the risk: and age of disease onset in the family member with the diagnosis affects a patient’s relative risks e.g. if age of onset is 70 the relative risk is 4 fold, if the age of onset is 50 the relative risk is increased 7 fold.

• High dietary fat intake increases the relative risk by 2 fold.

• Exposure to cadmium increases the risk, which found in cigarette smoke, alkaline batteries, and in the welding industries

PathologyPathology

• Over 95% of the cancers are adenocarcinoma, others e.g.– transitional cell carcinoma– small cell carcinoma– sarcoma.

• Histological classification commonly used is (Gleason)

(Relies upon the lower power appearance of the glandular architecture under the microscope). In which we have 5 grades.

SpreadSpreadLocal spread:

seminal vesicles, bladder neck, trigon, and distal urethral sphincter, involving the trigon may obstruct of one or both ureter may result in anuria if bilateral. Rectal involvement is rare as denonvillier’fascia represent a strong barrier. But may become stenosed by tumor infiltrating around it.

Spread by the bloodstream:

Particularly to bones (most common site of origin for skeletal metastasis is CaP ),most frequently the pelvic bones and the lower lumbar vertebrae , femoral head ,rib cage and the skull.

Lymphatic spread: spreads to obturator lymph nodes and internal iliac and external iliac and common iliac lymph nodes and to the presacral lymph nodes. And periaortal lymphnodes.

Types of prostate cancerTypes of prostate cancer

• Microscopic latent cancer found on autopsy or at cystoprostatectomy.

• Tumors found incidentally during TURP or following screening by PSA (T1a and T1b)

• Early, localized prostate cancer (T2).

• Advanced local prostate cancer (T3-T4)

• Metastatic disease either originate from apparent tumor or from occult prostate cancer (apparently benign gland)(T0-T1)

Clinical features

• Most patients with early stage CaP are asymptomatic. The presence of symptoms often suggests locally advanced or metastatic disease.

Symptoms of advanced disease include:

• BOO (IVS and OVS), pelvic pain and hematuria, bone pain malaise, anemia, renal failure (uremia), urinary and fecal incontinence.

Early disease usually found incidentally following TURP for BPH, or by DRE

suspicion of prostate cancer :

– because of either local findings (DRE)noduleindurations diffuse hardness of the prostate).

– raised PSA (>10ng/ml highly suspicious ),• 4-10 ng/ml suspicious • below 4 ng/ml regard as normal ),

then transrectal ultrasound guide sextant biopsy taken

Lab findingsLab findings

• Uremia can result from bilateral ureteral obstruction either from direct extension into the trigon or from retroperitoneal adenopathy.

• Anemia may be present in metastatic diseas.

• Alkaline phosphatase may be elevated in the presence of bone metastasis, or extensive liver metastasis.

• Serum acid phosphatase may be elevated with disease outside the confines of the prostate.

• PSA is a useful as tumor marker for – screening, – Staging e.g. >20ng/ml go with advanced disease <10ng/ml most of the

case localized tumor– evaluate respond to the treatment (follow up).

• CXR for lung, or ribs metastasis, abdominal X-ray for lumbar and pelvic bone metastasis which is commonly osteoblastic.

• Ultrasound and IVP for evaluation of the upper urinary tract.

• Bone scan if PSA >20ng/ml in which performed by injection of technetium-99m which is then monitored using gamma camera.

staging the tumorstaging the tumor

stagingstaging• TRUS is useful in performing prostatic biopsy and in providing some

useful local staging information if cancer is detected. If visible CaP tends to appear as a hypoechoic lesion in the peripheral zone.

• Endorectal MRI used for local staging also has high accuracy.

• CT, MRI of the pelvis in patients with CaP is selectively performed to exclude lymph node metastasis in high risk.– CT-guided fine-needle aspiration.

Antibody imaging—ProstaScint is a murine monoclonal antibody to an intracellular component of the prostate-specific membrane antigen (PSMA), which is conjugated to 111 indium.

However, this antibody recognizes the intracellular domain of PSMA; only soft tissues are imaged

DDXDDX

• Factors leads to elevation of PSA include– (BPH– urethral instrumentation– prostatitis, prostatic infarction– vigorous prostatic massage).

• indurations of prostate others as – (chronic granulomatous prostatitis– previous TURP– previous needle biopsy– prostatic calculi

Treatment decision are based on• Grade• Stage• Life expectancy• Ability of each therapy to ensure

– disease free survival – Associated morbidity– Patient and physician preferences

TreatmentTreatment

A. localized disese(T1-T2):

1.watchful waiting (surveillance):For highly selected patients with CaP, old age with limited life expectancy, concomitant illnesses, small, well differentiated tumor.(cancer death rate 10%)

2. Radical prostatectomy (RP):Includes removal of prostate+seminal vesicles +pelvic lymphadenectomy and anastomosis of bladder to the membranous urethra can be performed

– Retropubically– Perinealy – Laparoscopically.

Complications of RPComplications of RP

• Immediate includes

– blood loss– rectal injury– ureteral injury– and perioperative complications include

• DVT• pulmonary embolism• lymphocele formation • wound infection.

• Late complications include – urinary incontinence– impotence

Localized diseaseLocalized disease

3. Radiation therapy –external beam therapyBy 3 dimensional conformal radiotherapy (CT guided), in which use 3 dimensional treatment planning software. In which treatment field accurately placed allow higher dose of radiation to be given without exceeding the tolerance of surrounding normal tissue

4. Radiation therapy- brachytherapy :Deliver a very high dose of radiation to a localized area . and this by placing radioactive seeds under TRUS guidance.

Localized diseaseLocalized disease

5. Cryosurgery:

By freezing of the prostate by using a multiprobe cryosurgical

device, percutaneously under TRUS guide,

B. locally advanced disease

Most patients with T3 cap are treated with neoadjuvant hormonal therapy followed by XRT.

D.metastatic diseaseD.metastatic disease

Endocrine therapy:• Most of the prostatic carcinoma are hormone dependant and 70-

80% of men with metastatic cap respond to various forms of androgen deprivation.

• Androgen deprivation may be induced at several levels along the pituitary-gonadal axis using variety of methods or agents:

Level Agent route Dose(mg) Frequency

Pituitary DiethylstilbesterolGoserlinGoserlinLeuprolideLeuprolide

OralSCSCIMIM

1-310.8

3.622.5

7.5

DailyEvery 3 month

Every monthEvery 3month

Every month

Adrenal Ketoconazole Oral 400 Daily

Testicle Orchiectomy

Prostate cell

BicalutamideFlutamide

Nilutamide

OralOralOral

50250150

Daily3 times a day

daily

• Current administration of LHRH agonists and orchiectomy are the most common form of primary androgen blockade used.

• Suppression of both testicular and adrenal androgens (complete androgen blockade. And this can be achieved by LHRH agonist+ antiandrogen.

• Antiandrogen appear to act by competitively binding the receptor for DHT the intratesticular androgen responsible for prostate cell growth and development.