Neoplasms of the Prostate Gland Dr. Kaveh Mehravaran Urologist, Fellowship of Endourology & Laparoscopy Hasheminejad Hospital

BENIGN PROSTATIC HYPERPLASIA Incidence & Epidemiology BPH is the most common benign tumor in men, and its incidence is age related. The prevalence of histologic BPH in autopsy studies rises from approximately 20% in men aged 41–50, to 50% in men aged 51–60, and to >90% in men older than 80.

Etiology The etiology of BPH is not completely understood, but it seems to be multifactorial and endocrine controlled. The prostate is composed of both stromal and epithelial elements, and each, either alone or in combination, can give rise to hyperplastic nodules and the symptoms associated with BPH.

Pathophysiology One can relate the symptoms of BPH to either the obstructive component of the prostate or the secondary response of the bladder to the outlet resistance.

Clinical Findings SYMPTOMS The symptoms of BPH can be divided into obstructive and irritative complaints. Obstructive symptoms include hesitancy, decreased force and caliber of stream, sensation of incomplete bladder emptying, double voiding (urinating a second time within 2 hours of the previous void), straining to urinate, and post-void dribbling. Irritative symptoms include urgency, frequency, and nocturia.

SIGNS A physical examination, DRE, and focused neurologic examination are performed on all patients.

LABORATORY FINDINGS A urinalysis to exclude infection or hematuria and serum creatinine measurement to assess renal function are required. Serum PSA is considered optional, but most physicians will include it in the initial evaluation.

IMAGING Upper-tract imaging (intravenous pyelogram or renal ultrasound) is recommended only in the presence of concomitant urinary tract disease or complications from BPH (eg, hematuria, urinary tract infection, renal insufficiency, history of stone disease).

Differential Diagnosis Other obstructive conditions of the lower urinary tract, such as urethral stricture, bladder neck contracture, bladder stone, or CaP, must be entertained when evaluating men with presumptive BPH. A urinary tract infection, which can mimic the irritative symptoms of BPH Although irritative voiding complaints are also associated with carcinoma of the bladder, especially carcinoma in situ, the urinalysis usually shows evidence of hematuria. Likewise, patients with neurogenic bladder disorders may have many of the signs and symptoms of BPH, but a history of neurologic disease, stroke, diabetes mellitus, or back injury may be present as well.

Treatment WATCHFUL WAITING watchful waiting is the appropriate management of men with mild symptom scores Men with moderate or severe symptoms can also be managed in this fashion if they so choose.

Alpha-blockers

5-Alpha-reductase inhibitors

Phytotherapy Several plant extracts have been popularized, including the saw palmetto berry, (Serenoa repens) the bark of Pygeum africanum, the roots of Echinacea purpurea

CONVENTIONAL SURGICAL THERAPY Transurethral resection of the prostate(TURP) Transurethral incision of the prostate Open simple prostatectomy Laser therapy Transurethral electrovaporization of the prostate Hyperthermia Transurethral needle ablation of the prostate High-intensity focused ultrasound Intraurethral stents

CARCINOMA OF THE PROSTATE Incidence & Epidemiology Prostate cancer is the most common cancer detected in American men. The lifetime risk of a 50-year-old man for latent CaP (detected as an incidental finding at autopsy, not related to the cause of death) is 40%; for clinically apparent CaP, 9.5%; and for death from CaP, 2.9%. Several risk factors for prostate cancer have been identified. increasing age heightens the risk for CaP. African Americans are at a higher risk for CaP than whites. A positive family history of CaP also increases the relative risk for CaP.

Epidemiologic studies have shown that the incidence of clinically significant prostate cancer is much lower in parts of the world where people eat a predominantly low fat, plant-based diet.

Pathology Over 95% of the cancers of the prostate are adenocarcinomas. Of the other 5%, 90% are transitional cell carcinomas, and the remaining cancers are neuroendocrine (“small cell”) carcinomas or sarcomas. Approximately, 60–70% of cases of CaP originate in the peripheral zone, while 10–20% originate in the transition zone, and 5–10% in the central zone.

Grading & Staging The Gleason score or Gleason sum is obtained by adding the primary and secondary grades together. As Gleason grades range from 1 to 5, Gleason scores or sums thus range from 2 to 10. Well-differentiated tumors have a Gleason sum of 2–4, moderately differentiated tumors have a Gleason sum of 5–6, and poorly differentiated tumors have a Gleason sum of 8–10.

Patterns of Progression The likelihood of local extension outside the prostate (extracapsular extension) or seminal vesicle invasion and distant metastases increases with increasing tumor volume and more poorly differentiated cancers. Lymphatic metastases are most often identified in the obturator lymph node chain. The axial skeleton is the most usual site of distant metastases, with the lumbar spine being most frequently Implicated Visceral metastases most commonly involve the lung, liver, and adrenal gland.

Clinical Findings SYMPTOMS Most patients with early-stage CaP are asymptomatic. The presence of symptoms often suggests locally advanced or metastatic disease. Obstructive or irritative voiding complaints can result from local growth of the tumor into the urethra or bladder neck or from its direct extension into the trigone of the bladder. Metastatic disease to the bones may cause bone pain. Metastatic disease to the vertebral column with impingement on the spinal cord may be associated with symptoms of cord compression, including paresthesias and weakness of the lower extremities and urinary or fecal incontinence.

A physical examination, including a DRE, is needed. Induration, if detected, must alert the physician to the possibility of cancer and the need for further evaluation Locally advanced disease with bulky regional lymphadenopathy may lead to lymphedema of the lower extremities. Specific signs of cord compression relate to the level of the compression and may include weakness or spasticity of the lower extremities and a hyperreflexic bulbocavernosus reflex.

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.

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.

PSA velocity PSA density Age-adjusted reference ranges for PSA Molecular forms of PSA

PROSTATE BIOPSY Prostate biopsy is best performed under TRUS guidance using a spring-loaded biopsy device coupled to the imaging probe.

IMAGING TRUS Endorectal magnetic resonance imaging (MRI) Axial imaging (CT, MRI) Bone scan Antibody imaging

Treatment LOCALIZED DISEASE Watchful waiting and active surveillance Radical prostatectomy Radiation therapy (Brachytherapy- external beam therapy) Cryosurgery and high-intensity focused ultrasound (HIFU)

METASTATIC DISEASE Initial endocrine therapy