Prostate Cancer Diagnosis

  • Diagnosis

    Prostate cancer is a very common problem as men age Figure 01. It has been estimated that 234,460 men would be diagnosed with the disease in 2006. The prostate is a walnut-sized gland that produces a thick fluid that forms the major part of semen. It is located below the bladder, in front of the rectum, and surrounds the upper part of the urethra (the tube that delivers urine from the bladder to the tip of the penis). Under the influence of the male hormone testosterone, prostate cells sometimes become cancerous and undergo unregulated growth. These cancer cells may spread beyond the prostate gland and invade (metastasize to) other parts of the body.

    Click to enlarge: The Prostate Gland

    Figure 01. The Prostate Gland

    Although it may be fatal, prostate cancer is usually so slow-growing that most men do not die from it. Prostate cancer is the most common cancer in males. It is second only to lung cancer as a cause of death for men in the U.S. Because prostate cancer incidence is highest in males in their seventies and eighties, and because prostate cancer is relatively slow-growing, many men with prostate cancer die from other causes. Therefore, considerable controversy exists about treatment options for prostate cancer that may cause impotence or incontinence.

    Cancer involves a process of abnormal cell growth. When cells become cancerous, their appearance changes and they undergo rapid growth and division. The resulting increase in tissue mass can press on surrounding areas. When the growth occurs on the prostate, it may constrict the urethra and cause urinary symptoms. The cancerous cells can also spread out of the prostate gland and travel to other parts of body. The cancerous cells travel via the bloodstream and lymphatic system in a process known as metastasis. Prostate cancer commonly metastasizes to the bones and lymph nodes. Cancer that has metastasized has a poor chance of cure.

    While no one knows why some men develop the disease, dietary factors seem to play a part. Because so many American men develop prostate cancer, some doctors regard prostate cancer as almost a normal process of aging. However, rates differ between countries, with the highest rates in North America, Western Europe, and Australia, and the lowest rates in the Far East and the Indian subcontinent. Racial groups within the U.S. also differ significantly, with African-Americans having the highest rates, followed by European-Americans. After one to two generations, the incidence of prostate cancer in Asian-Americans rises to a rate similar to that of Caucasians in the U.S. Population studies have shown rates of prostate cancer to be increased in those with a high-fat diet and with high dairy and calcium consumption, and to be reduced in those with a high intake of tomato products, vitamin E, and selenium. Cigarette smoking is associated with more aggressive disease.

    Prostate cancer usually causes no symptoms until it is quite advanced. Some men notice difficulties with urinating Table 01. Most men with prostate cancer notice no symptoms. Usually the extra tissue growth is small, or does not impinge on other structures, and therefore causes no symptoms. If the extra growth presses on the urethra, men typically experience difficulty urinating. This may involve a sense of urgency, difficulty starting the flow of urine, a slow or intermittent stream, or painful or burning sensations while urinating. Many men notice that they must get up several times during the night to urinate. These symptoms can also be caused by benign prostatic hyperplasia, or BPH, a non-cancerous enlargement of the prostate. Prostate cancer may also occasionally involve painful ejaculation, and blood may be evident in urine or semen.

    In cases of advanced cancer that has metastasized, bone pain and symptoms of generalized ill health may be apparent. Once cancer has metastasized to bone, it typically causes progressive back pain or sciatica (nerve pain or tingling in the legs). Cancer that has spread also leads to weight loss, fatigue, and weakness.

    Table 1.   Symptoms of Prostate Cancer

    Difficulties with urination Difficulties with ejaculation Advanced (metastasized) disease
    UrgencyDifficulty initiating flowSlow or intermittent streamPainful or burning sensationsFrequency, especially at nightBlood in urine Painful ejaculationBlood in ejaculate Bone painNerve pain or tingling in legsWeight lossFatigueWeakness

    Prostate cancer is common in American men; African-Americans have an especially high risk. Latent prostate cancer cells are found in a majority of men who are over the age of 65 at autopsy. These cells, however, do not cause disease. Latent prostate cancer is present in a significant number of Asians as well as Europeans, although the incidence is lower in Asians. It is felt that an additional genetic event is required to activate latent prostate cancer to become clinical prostate cancer. Prostate cancer was estimated to cause 27,350 deaths in 2006.

    The risk of prostate cancer increases with age; usually men are between the ages of 60 and 70 when diagnosed. African-Americans are more likely to get the disease at a younger age, and to have a more virulent course. Prostate cancer also seems to run in some families.

    To detect prostate cancer during a physical examination, a doctor will perform a digital rectal exam (DRE). Wearing a glove, the doctor coats his index finger with lubricating jelly before inserting it into the patient's rectum. The tip of his finger can then palpate the prostate, which should feel uniformly firm and about the size of a walnut. The doctor suspects prostate cancer if the gland feels enlarged, if it is asymmetric, if it has nodules, or if it has a uneven texture. The exam is somewhat uncomfortable, but takes less than a minute.

    A prostate-specific antigen (PSA) blood test can also detect evidence of prostate cancer. A prostate-specific antigen (PSA) blood test measures a protein called prostate-specific antigen, which is made only by prostate cells. The amount is proportional to the total volume of prostate epithelial cells, and also increases with the presence of an irritation, such as cancer or an inflammation. PSA is normally found in men at low levels, with less than 4.0 ng/mL considered normal. Higher levels or an increase of 0.7 ng/mL or more in one year is suggestive of the development of prostate cancer. Also, the level of PSA rises with aging, probably related to the increase in prostate size with aging.

    The PSA test does not detect all cases of prostate cancer, as 20% of men with prostate cancer have a “normal” PSA. It also is not specific: only one-fourth of men with an abnormal PSA actually have cancer. PSA levels can be elevated by factors other than cancer, including:

    • Ejaculation within 48 hours before the test
    • DRE within 24 hours of test
    • An enlarged prostate that does not contain cancer (benign prostatic hypertrophy). This is by far the most common cause of an elevated PSA not due to cancer
    • Inflammation of the prostate

    To increase the specificity of the PSA test, a free/total PSA ratio can be measured. PSA exists in blood in a free form as well as bound to proteins. Recent studies have shown that men with PSAs in the 4-10 ng/mL range, a free/total PSA of greater than 25%, indicates a high probability of the presence of benign disease; usually BPH rather than cancer. Such patients can be followed with repeat PSAs rather than biopsied.

    If cancer is suspected by DRE or PSA, a urologist will perform a biopsy. An abnormal DRE or PSA warrants a referral to a urologist, who performs a surgical removal of a small sample of prostate tissue (biopsy). This is accomplished by inserting a needle through the rectum, guided by a special ultrasound device inserted in the rectum. This outpatient procedure is performed in the doctor's office and does not require anesthesia. Most patients tolerate the procedure well, with possible mild rectal spotting or blood in the urine or sperm following the test. Antibiotics are given to prevent infection.

    A pathologist examines the tissue samples under a microscope. If cancer cells are found, they are “graded” by how similar they look to normal prostate. This grading process is called the “Gleason score”. More atypical, or “high-grade,” cells indicate a cancer more likely to grow quickly and spread. Pathologists commonly grade the tumor by giving it a Gleason score. With this system, a score of 2 to 4 indicates low aggressiveness; 5 to 6 indicates moderate aggressiveness; and 7 to10, an aggressive tumor with the poorest prognosis.

    If cancer cells are detected, further tests are done to determine whether the disease has spread beyond the prostate gland. This is called staging. Tests to determine if the cancer has spread may include a thorough physical exam, a CT scan or MRI, a bone scan, and a chest x-ray.

    The physical exam and associated tests will help determine the stage of your cancer Table 02. Prostate cancer is staged by its severity. Stages A and B represent localized cancer; that is, cancer that is limited to the prostate. Stage C represents cancer that has begun to spread locally outside the prostate, and stage D refers to cancer that has spread beyond the gland.

    Table 2.   Staging of Prostate Cancer

    European and International Staging U.S. Staging Disease Involvement
    T-1a A1 Nonpalpable upon digital rectal examination; disease is focal and limited to the prostate
    T-1b A2 Nonpalpable; disease is diffuse but confined to the prostate gland
    T-1c T-1c Nonpalpable; disease is diffuse but not confined to the prostate gland. Picked up on screening test for PSA is high?diagnosed and biopsied as cancer
    T-2a B1 Palpable, focal, and limited to one lobe
    T-2b B2 Palpable, diffuse (both lobes), but confined to the prostate
    T-3T-4T-4 C Palpable; extends outside of the prostate; may be fixed and have seminal vescicle involvement
    N D1 Usually palpable, evidence of regional (pelvic) node involvement
    M D2 Evidence of distant metastasis, usually to bone

    Early detection and treatment reduces death rates of prostate cancer. However, experts are divided over whether healthy men should be routinely screened. Detection of prostate cancer has increased in the U.S. since the widespread use of the DRE exam and the PSA blood test. Cancer can now be found in earlier stages, when the possibility of a cure is greater. For these reasons, the American Cancer Society and the American Urological Association recommends an annual prostate cancer DRE and PSA test to men who:

    • Are over age 50,
    • Are over age 40 if there is a family history of disease,
    • Are over age 40 if African-American,
    • Have warning signs: difficulty urinating, frequent trips to bathroom at night, pelvic discomfort, weight loss, persistent back pain.

    However, the U.S. Preventive Services Task Force, which also issues guidelines concerning screening procedures, recommends against the use of routine prostate cancer screening in men who have no symptoms of the disease. Experts who share this point of view argue that early detection in such cases has little or no proven benefit, because most men with prostate cancer do not die from their disease. Screening will therefore most frequently identify a cancer that may never cause symptoms or may not decrease a man's life expectancy. Because potential side effects of treatments can seriously compromise a man's quality of life, the benefits do not justify the costs, both in terms of resource expenditure and human suffering.

    An NIH-sponsored 15-year controlled trial is currently under way to determine who should be screened and when.

  • Prevention and Screening

    Early detection and treatment reduces death rates of prostate cancer. However, experts are divided over whether healthy men should be routinely screened. Detection of prostate cancer has increased in the U.S. since the widespread use of the DRE exam and the PSA blood test. Cancer can now be found in earlier stages, when the possibility of a cure is greater. For these reasons, the American Cancer Society and the American Urological Association recommends an annual prostate cancer DRE and PSA test to men who:

    • Are over age 50,
    • Are over age 40 if there is a family history of disease,
    • Are over age 40 if African-American,
    • Have warning signs: difficulty urinating, frequent trips to bathroom at night, pelvic discomfort, weight loss, persistent back pain.

    However, the U.S. Preventive Services Task Force, which also issues guidelines concerning screening procedures, recommends against the use of routine prostate cancer screening in men who have no symptoms of the disease. Experts who share this point of view argue that early detection in such cases has little or no proven benefit, because most men with prostate cancer do not die from their disease. Screening will therefore most frequently identify a cancer that may never cause symptoms or may not decrease a man's life expectancy. Because potential side effects of treatments can seriously compromise a man's quality of life, the benefits do not justify the costs, both in terms of resource expenditure and human suffering.

    An NIH-sponsored 15-year controlled trial is currently under way to determine who should be screened and when.

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