Carcinoma of the Prostate Prof. Saad Dakhil

Prostate Cancer Definition Relevance –Most common noncutaneous malignancy in men Incidence –Nearly 200,000 new cases per year in U.S. Mortality –32,000 deaths in the United States each year –Second most common cause of cancer death in men 2 Morbidity –Single histologic disease –Ranges From indolent, clinically irrelevant To virulent, rapidly lethal phenotype.

Prostate Cancer Epidemiology Risk factors –Increasing age –Family history –African-American –Dietary factors. Nutritional factors have protective effect against prostate cancer –Reduced fat intake –Soy protein –Lycopene –Vitamin E –Selenium Race –Incidence doubled in African Americans compared to white Americans. Genetics –Common among relatives with early-onset prostate cancer –Susceptibility locus (early onset prostate cancer) Chromosome 1, band Q24 –An abnormality at this locus occurs in less than 10% of prostate cancer patients.

Pathology ADENOCARCINOMA Adenocarcinoma of the prostate is multifocal in more than 85% of cases. the major tumor mass is peripheral in location 85% of non palpable tumors diagnosed on needle biopsy.

Prostate Cancer Clinical Manifestations Early state (organ confined) –Asymptomatic Locally advanced –Obstructive voiding symptoms Hesitancy Intermittent urinary stream Decreased force of stream –May have growth into the urethra or bladder neck –Hematuria –Hematospermia Advanced (spread to the regional pelvic lymph nodes) –Edema of the lower extremities –Pelvic and perineal discomfort

Symptoms

Prostate Cancer Clinical Manifestations Metastasis –Most commonly to bone (frequently asymptomatic) Can cause severe and unremitting pain –Bone metastasis Can result in pathologic fractures or Spinal cord compression –Visceral metastases (rare) –Can develop pulmonary, hepatic, pleural, peritoneal, and central nervous system metastases late in the natural history or after hormonal therapies fail. Small, E., Cecil Textbook of Medicine, Prostate Cancer, 2004, WB Saunders, an Elsevier imprint

Diagnosis

Prostate Cancer Detection with DRE & PSA Method of Detection Percentage of Cancer Detected DRE Alone 18% PSA Alone 45% Both DRE and PSA Over 80% A high PSA does not automatically mean prostate cancer

TUMOR MARKERS PROSTATE-SPECIFIC ANTIGEN PSA is a serine protease produced by benign and malignant prostate tissues. It circulates in the serum as uncomplexed (free or unbound) or complexed (bound) forms. Normal PSA values are those ≤4 ng/mL. Current detection strategies include the efficient use of the combination of DRE, serum PSA, and TRUS with systematic biopsy. Unfortunately, PSA is not specific for CaP, as other factors such as BPH, urethral instrumentation, and infection can cause elevations of serum PSA.

Transrectal ultrasonography (TRUS ) Different CaPs appear differently on TRUS. The classic picture of a hypoechoic area in the peripheral zone of the prostate will not always be seen. TRUS has two potential roles in the diagnosis of CaP: 1. To identify lesions suspected of malignancy. 2. To improve the accuracy of prostate biopsy.

PROSTATE BIOPSY Prostate biopsy should be considered in men with an elevated serum PSA, a DRE, or a combination of the two

LABORATORY FINDINGS Azotemia can result from bilateral ureteral obstruction either from direct extension into the trigone or from retroperitoneal adenopathy. Anemia may be present in metastatic disease. Alkaline phosphatase may be elevated in the presence of bone metastases. Serum acid phosphatase may be elevated with disease outside the confines of the prostate.

IMAGING 1. Bone scan When prostate cancer metastasizes, it most commonly does so to the bone, 2. Endorectal magnetic resonance imaging (MRI). 3. Axial imaging (CT, MRI)

Screening for CaP The case for CaP screening is supported by the following: most PSA-detected tumors are curable; prostate cancer mortality is declining in regions where screening occurs; and curative treatments are available. If screening is undertaken, it appears that the use of both DRE and serum PSA is preferable to either one used alone.

Grading & Staging The Gleason grading system is the most commonly employed grading system in the United States. It is truly a system that relies upon the low-power appearance of the glandular architecture under the microscope.

Staging

Prostate Cancer Staging Stage T1 –Nonpalpable prostate cancer –Detected only on pathologic examination Incidentally noted after –Transurethral resection for benign hypertrophy (T1a and T1b) or –On biopsy obtained because of an elevated PSA (T1c-the most common clinical stage at diagnosis) Stage T2 –Palpable tumor –Appears to be confined to the prostatic gland (T2a if one lobe, T2b if two lobes) Stage T3 –Tumor with extension through the prostatic capsule (T2a if focal, T2b if seminal vesicles are involved) Stage T4 –Invasion of adjacent structures Bladder neck External urinary sphincter The rectum The levator muscles The pelvic sidewal Nodal metastases –Can be microscopic and can be detected only by biopsy or lymphadenectomy, or they can be visible on imaging studies Distant metastases –Predominantly to bone –Occasional visceral metastases occur. Small, E., Cecil Textbook of Medicine, Prostate Cancer, 2004, WB Saunders, an Elsevier imprint

Treatment A. LOCALIZED DISEASE General considerations. Currently, treatment decisions are based on the grade and stage of the tumor, the life expectancy of the patient, the ability of each therapy to ensure disease-free survival, its associated morbidity, and patient and physician preferences. Types: 1-Watchful waiting and active surveillance. 2. Radical prostatectomy. 3. Radiation therapy—external beam therapy. 4. Radiation therapy—brachytherapy. 5. Cryosurgery and high-intensity focused ultrasound (HIFU).

Brachytherapy

1-Watchful waiting and active surveillance. The term deferred treatment or watchful waiting (WW) is used to describe a treatment strategy that includes an active standpoint to postpone treatment until it is required. (stage T1-T2, Nx-N0, M0) well and moderately differentiated tumours. In asymptomatic patients with a life expectancy of < 10 years.

2-RADICAL PROSTATECTOMY The surgical treatment of CaP consists of radical prostatectomy, meaning the removal of the entire prostate gland between urethra and bladder, with resection of both seminal vesicles. The procedure is routinely performed either retropubically. a transperineal approach. laparoscopic radical prostatectomy. Also, a robotic radical prostatectomy.

Laparoscopic and robotic radical prostatectomy

Indications In patients with stage T1b-T2, Nx-N0, M0 disease and a life expectancy >10 years. Currently, radical prostatectomy is the only treatment for localized CaP that has shown a cancer-specific survival benefit when compared to conservative management.

4- RADIATION THERAPY Traditional external beam radiotherapy (XRT). novel treatment :three-dimensional, conformal, and intensity-modulated radiation therapy). In localized CaP T1c-T2c N0 M0, is recommended, even for young patients who refuse surgical intervention. 5. Radiation therapy—brachytherapy:place radioactive seeds under TRUS guidance. 6. Cryosurgery :Freezing of the prostate is carried out by using a multiprobe cryosurgical device. 7- high-intensity focused ultrasound (HIFU).:HIFU can be delivered to the prostate using a rectal probe. This technology induces coagulative necrosis of benign and malignant prostate tissue.

Metastatic Disease HORMONAL THERAPY

Introduction Prostate cells are physiologically dependent on androgens to stimulate growth, function and proliferation. Testosterone, although not tumourigenic, is essential for the growth and perpetuation of tumour cells. The testes are the source of the vast majority of the androgens with only 5 to 10% –– deriving from adrenal biosynthesis. If prostate cells are deprived of androgenic stimulation, they undergo apoptosis (programmed cell death).

Types Androgen deprivation can be achieved either by suppressing the secretion of testicular androgens by means of surgical or medical castration, or by inhibiting the action of the circulating androgens at the level of their receptor in prostate cells using competing compounds known as antiandrogens.

Castration 1-Bilateral orchiectomy: Surgical removal of both testicles. 2-Oestrogens :The most commonly used oestrogen is diethylstilboestrol (DES). 3-Luteinizing hormone-releasing hormone (LHRH) agonists and antigonsts. 4-Antiandrogens :Antiandrogens compete with testosterone and DHT for binding sites on their receptors in the prostate cell nucleus, thus promoting apoptosis and inhibiting CaP growth.

Side Effects Of Hormonal Therapy Loss of libido None. Erectile dysfunction. “Hot flashes”. Gynaecomastia and breast pain, Increase in body fat Muscle wasting. Anaemia. Decrease in bone mineral density, calcium, vitamin D. Cognitive decline.