Anatomy

The prostate lies below the bladder and encompasses the prostatic urethra. It is surrounded by a capsule and is separated from the rectum by a layer of fascia termed the Denonvilliers aponeurosis. (See the image below.)

Management of localized prostate cancer. This diagram depicts the relevant anatomy of the male pelvis and genitourinary tract.

The inferior vesical artery, which is derived from the internal iliac artery, supplies blood to the base of the bladder and prostate. The capsular branches of the inferior vesical artery help identify the pelvic plexus arising from the S2-4 and T10-12 nerve roots. The neurovascular bundle lies on either side of the prostate on the rectum. It is derived from the pelvic plexus and is important for erectile function.
Diagnosis
With the introduction of PSA into clinical practice in the late 1980s and the subsequent influential recommendations of the American Urological Society and the American Cancer Society, prostate cancer screening (PSA plus digital rectal examination [DRE]) has become widely used in the United States. Prostate cancer screening remains controversial, as evidenced by the wide array of screening recommendations (Box 1), because there is no prospective evidence demonstrating a decrease in prostate cancer-specific mortality.
2

Box 1: Summary of Current Prostate Cancer Guidelines From Selected Organizations

American College of PhysiciansAmerican Society of Internal Medicine

Physicians should describe potential benefits and known harms of screening, diagnosis, and treatment, listen to the patient's concerns, and then individualize the decision to screen.

American Cancer Society and American Urological Association

Physicians should offer annual DRE and PSA screening, beginning at age 50 years, to men who have at least a 10-year life expectancy and to younger men at high risk.

Canadian Task Force on Preventive Health Care and U.S. Preventive Services Task Force

DRE and PSA tests are not recommended for the general population.

American Academy of Family Physicians

No published standards or guidelines are available for low-risk patients.

American Medical Association

Physicians should provide information regarding the risks and potential benefits of prostate screening.

DRE, digital rectal examination; PSA, prostate-specific antigen.

Several prospective screening trials are ongoing in the United States and worldwide. Among the largest are the European Randomized Screening for Prostate Cancer (ERSPC) trial, with more than 160,000 men, and the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO), sponsored by the National Cancer Institute, which completed enrolment of more than 154,000 participants, including 75,000 men, in the summer of 2001. It is hoped that the results of these trials will provide more definitive guidance to patients and clinicians about the impact of screening. Until more definitive data are available, many major medical societies have recommended a careful discussion with individual patients, before screening, regarding the potential risks and benefits. Patients with significant comorbid conditions and those with life expectancies of less than 10 years are much less likely to benefit from therapeutic intervention and therefore should not be considered for screening. Alternatively, patients at potentially high risk, such as African Americans and those with one or more affected first-degree relatives, might be appropriate candidates for screening at an earlier age, 40 to 50 years.

Over the last decade, the penetration of PSA-based screening has caused a stage migration, with an increasing percentage of patients with normal rectal examination findings receiving a diagnosis on the basis of an elevated PSA level (clinical stage T1c in the tumor, node, metastasis [TNM] staging classification). There has also been a concomitant dramatic decrease in the number of patients who present initially with evidence of metastatic disease.

Following a biopsy-proven diagnosis of prostate cancer, patients are clinically staged using the TNM system (Table 1) based on the extent of local tumor on rectal examination and the presence or absence of metastatic disease. In the last several years, a series of outcomes-based nomograms have been developed to improve the clinician's ability to predict the patient's pathologic stage (http://urology.jhu.edu/prostate/partintables.php) and his response to therapy (http://www.mskcc.org/mskcc/html/10088.cfm). These nomograms use clinically available parameters such as PSA, Gleason scores obtained from prostate biopsies or surgery, and other known prognostic factors, such as prostate capsule penetration, margin status, involvement of the seminal vesicles, and node status.

Table 1: TNM Clinical Stages of Prostate Cancer

Stage Features

T1a

Nonpalpable, with %5% of tissue with cancer, low grade (diagnosed by transurethral resection of the prostate)

T1b

Nonpalpable, with >5% of tissue with cancer, high grade (diagnosed by transurethral resection of the prostate), or both

T1c

Nonpalpable, but prostate-specific antigen level elevated

T2a

Palpable, one half of one lobe or less

T2b

Palpable, more than one half of one lobe, not both lobes

T2c

Palpable, involves both lobes

T3a

Palpable, unilateral capsular penetration

TNM, tumor, node, metastasis.

Signs and symptoms

The clinical manifestations of prostate cancer result from the effects of local growth of the tumor, the spread to regional lymph nodes via the lymphatics, and the hematogenous dissemination to distant metastatic sites.

Although most patients with early-stage prostate cancer are asymptomatic, locally advanced disease can lead to obstructive or irritative voiding symptoms that result from local tumor growth into the urethra or bladder neck, extension into the trigone of the bladder, or both.

Prostate cancer most often spreads to bone, commonly leading to bone pain. A small but important subset of patients develop spinal cord impingement from the epidural spread of disease, resulting in pain and neurologic compromise that, depending on the location of the spinal lesion, could include the irreversible loss of bowel and bladder function and the ability to walk. Other common sites of metastatic spread include lymph nodes, with some patients presenting with progressive lymphedema, renal insufficiency, or both as a consequence of obstruction of pelvic lymphatics and ureteral outlet obstruction.

Symptoms
By Mayo Clinic staff Living With Cancer E-newsletter
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Sign up now Prostate cancer may not cause signs or symptoms in its early stages. Prostate cancer that is more advanced may cause signs and symptoms such as:

Trouble urinating Decreased force in the stream of urine

Blood in the urine Blood in the semen Swelling in the legs Discomfort in the pelvic area Bone pain
Definition
Prostate cancer has evolved from a relatively common but infrequently discussed neoplasm to a major clinical entity with significant public health and economic ramifications. The widespread application of prostate-specific antigen (PSA) into clinical practice in the late 1980s has had a paradigm-shifting impact on the management of prostate cancer. Among the most visible consequences of PSA-based screening is the substantial increase in the percentage of patients who are believed to have clinically localized disease. This, in turn, has translated into a significant increase in the number of patients undergoing curative-intent surgery and radiotherapy. Additional prostate cancer subsets have been created, including patients with PSA-only evidence of disease following curative-intent therapy, termed biochemical failure, and patients with rising PSA levels following androgen-deprivation therapy, termed castrate progressive prostate cancer, biochemically defined.

Prostate Cancer Causes

The cause of prostate cancer is unknown, but hormonal, genetic, environmental, and dietary factors are thought to play roles. The following risk factors have been linked with development of this condition:

Age: There is a strong correlation between increasing age and developing prostate cancer. The incidence of prostate cancer increases steadily from fewer than one in 100,000 for men 40 years of age to 1,146 per 100,000 in men 85 years of age. The median age at diagnosis of prostate cancer is 70.5 years of age. More than 80% of prostate cancers are diagnosed in men older than 65 years of age. Autopsyrecords indicate that 70% of men older than 90 years of age have at least one region of cancer in their prostate.

Race: African American men are 1.6 times more likely than white men to develop prostate cancer. They are also 2.4 times more likely to die from their disease as compared to white men of a similar age. Asian Americans, on the other hand, have a much lower chance of getting prostate cancer as compared to whites or African Americans. Although, these racial criteria have been used to study and describe the disease in the past, there is no defined biologic basis for this

classification. In other words, these differences in diagnosis and death rates are more likely to reflect a difference in factors like environmental exposure, diet, lifestyle, and health-seeking behavior rather than any racial susceptibility to prostate cancer. Recent evidence, however, suggests that this disparity is progressively decreasing with high chances of complete cure in men undergoing treatment for organ-confined prostate cancer (cancer that is limited to within the prostate without spread outside the confines of the prostate gland) irrespective of race.

Genetic factors: Men who have a history of prostate cancer in their family, especially if it was a first-degree relative such as a father or brother, are at an increased risk. This risk may be two to three times greater than the risk for men without a family history of the disease. Earlier age at diagnosis (<60 years of age) in a first-degree relative and disease affecting more than one relative also increases the risk for developing prostate cancer.

Infection: Recent evidence has suggested the role of sexually transmitted infections as one of the causative factors for prostate cancer. People who have had sexually transmitted infections are reported as having 1.4 times greater chance of developing the disease as compared to the general population.

Diet: A diet high in fat has been associated with an increased risk of prostate cancer.

Chemical agents: Exposure to chemicals such as cadmium has been implicated in the development of prostate cancer. There is also some evidence to suggest that obesity leads to an increased risk of having more aggressive, larger prostate cancer, which results in a poorer outcome after treatment.

There is no proven link between frequency of sexual activity and prostate cancer risk.