Introduction

Cancer of the prostate remains the most common cancer in men. It is estimated that this disease will be diagnosed in 198,100 Americans in the year 2001 and will lead to the death of approximately 31,500.

The risk increases with age, beginning to rise by age 50. In white men with a family history of prostate cancer in first-degree relatives and in African-Americans, the increased risk begins at age 40.

African-Americans have the highest incidence. The risk doubles if there is a first-degree relative with prostate cancer. There has been no definite proof of an association between prostate cancer and either fatty diet, vasectomy or sexually-transmitted diseases.

Despite its prevalence, there is no consensus adopted for screening, diagnosis or management of prostate cancer.

Screening and diagnosis

Early-stage disease is usually asymptomatic. In locally advanced disease, bladder outlet obstruction is usually present, often with hematuria and urinary tract infections. Bone metastasis can present with bone pain, spinal cord compression; manifested by lower extremity weakness, and bladder and bowel sphincter dysfunction; which is considered an oncologic emergency.

Prostate cancer screening is very controversial. Supporters for early detection efforts point to data that have shown that 75% of patients with localized prostate cancer will develop local extension within 10 years and of these individuals 65% will die. But those who are against screening assert that (1) early detection has not yet been shown to improve mortality and (2) there is lead-time bias -- indolent tumors detected early that would have not otherwise have changed the natural course of life for that individual. Although not yet conclusive; the emerging data support the concept that early detection can save lives.

The National Comprehensive Cancer Control recommends digital rectal exam (DRE) in all men who are 50 or older, and even younger if they have a high risk. PSA, a serine protease produced by the prostatic epithelium, should also be measured annually. PSA increases from inflammation of the prostate, urinary retention, prostatic infection, benign prostatic hyperplasia, prostate cancer and prostatic manipulation. A normal PSA is considered to be <4 ng/ml. A value between 4-10 ng/ml is classified as borderline and a value above 10 ng/ml is strongly suggestive of prostate cancer. PSA testing misses 18-25% of prostate cancer because of false negatives and produces false positive results approximately 60% of the time.

If DRE is abnormal or PSA is above 4ng/ml, the next step is biopsy guided by transrectal ultrasound. Complications include infection, hematuria and hematochezia.

Course of the disease

Adenocarcinoma is the most common type of prostate cancer, starting most often as a single focus in the peripheral zone of the prostate gland. Autopsy studies demonstrate that prostate cancer has a prolonged natural course, especially in early stages. Gleason's grading system, 1 to 5 with 5 being the most undifferentiated, provides the best prognostic information in addition to clinical stage. The score is the sum of the two most predominant patterns of tumor tissue.

Risk of Metastasis According to Gleason Score in Localized Prostate Cancer

Gleason Score	Risk of Developing Metastasis (%)
2-4	20
5-7	40
8-10	75

The TNM [T: tumor, N: lymph nodes, M: metastasis] system for staging is the one that is most commonly used. Briefly, T1 and T2 tumors are confined to the gland, whereas T3 and T4 tumors have local extension. Accurate staging is essential for establishing a treatment plan. While localized tumors with low Gleason scores are associated with a very small chance of mortality related to prostate cancer, the more advanced and poorly differentiated tumors carry a high chance of dying regardless of age.

Treatment

There is much controversy about treatment options. In clinical stage T1 and T2a, the recommended strategy of treatment for this group is observation with careful follow-up. If life expectancy is more than 20 years, then either radical prostatectomy or external beam radiation are options if the patient wishes to pursue the highest chance of cure. In the intermediate risk group, Gleason score 5-7, the choice is between radical prostatectomy and external radiation. If patient's life expectancy is less than 10 years, then observation alone may be an appropriate option.

When the risk of recurrence is deemed high, based on either a PSA >20 or Gleason score > 8 regardless of the stage, then hormone therapy, hormone therapy plus radiation or, in selected patients, radical prostatectomy (RP) are the treatment options. If life expectancy is <10 years, observation alone can be the appropriate choice. In metastatic disease, hormone therapy is advised.

In clinically localized disease, there is no evidence that RP improves survival in comparison with watchful follow-up. Specific complications are associated with RP: sexual dysfunction occurs in over 80% of patients, urinary incontinence in 30%, urethral stricture in 18%, fecal incontinence in 5% and 1% of patients will have bowel injury requiring repair.

External Beam Radiation (EBR), compared to RP, increases the risk of metastasis. Complications include impotence in 20-30% of patients, bowel dysfunction in 10% and urinary incontinence in 7%. Up to one-third of patients with clinically localized disease who were treated with radiation therapy still have a positive biopsy three years after treatment. Overall survival is estimated to be 85%.

In metastatic disease, the role of EBR may be limited to providing effective pain relief from bony metastases. In patients with node positive prostate cancer, androgen deprivation therapy (ADT), after RP and pelvic lymphadenectomy, has been shown to improve survival and reduce the risk of recurrence. There is no difference in effectiveness among different modes of ADT (orchiectomy, diethylstilbesterol "DES", luteinizing hormone releasing hormone (LHRH) agonists). Complications include vasomotor flushing, loss of libido, gynecomastia, weight gain, osteoporosis and loss of muscle mass. DES carries a risk for cardiovascular events, gastritis and allergic reactions. Orchiectomy has cosmetic and psychological consequences. LHRH agonists may cause initial flare because of transient increases in androgen levels.

Chemotherapy decreases pain and prolongs palliation in some men with symptomatic prostate cancer. It has no survival benefit. The agents that have been studied are mitoxantrone plus prednisone. A few men had febrile neutropenia; cardiac arrhythmia and CHF are two other rare complications.