Treatment of Distant (Metastatic) Disease

Hormone Therapy
Ninety-five percent of prostate cancer cells are hormonally sensitive. For this reason, if a patient’s source of testosterone is removed or blocked, the vast majority of prostate cancer cells will slow significantly in their growth. This is best accomplished either with drugs that alter the way hormones work or with surgery that removes the testicles (testes). This treatment is often used for patients whose prostate cancer has spread to other parts of the body or has recurred despite treatment. Hormone therapy also is used in combination with radiation therapy for intermediate or high-risk localized prostate cancer because it enhances the effects of radiation on prostate cancer cells. Hormone therapy by itself does not cure prostate cancer. Hormone therapy does slow the growth of the disease and lengthen the time before prostate symptoms become severe.

Orchiectomy
This operation removes the testicles. Although it is a surgical treatment, orchiectomy is considered a hormonal therapy because it works by removing the main source of male hormones. Orchiectomy temporarily prevents or reduces the growth of most prostate cancers.

Side Effects
Ninety percent of men who have had this operation have reduced or absent libido and impotence. Many men have hot flashes after surgery but these usually go away with time. Breast tenderness and growth of breast tissue may occur. The disadvantage of an orchiectomy is that the therapy is not reversible.

Luteinizing Hormone-releasing Hormone (LHRH) Analogs (Zoladex®, Lupron® or Viadur®)
These drugs decrease the amount of testosterone produced by a male's testicles. This medication, like an orchiectomy, is injected every one to four months or once per year at the doctor’s office. The drugs lower the level of testosterone as effectively as surgical removal of the testicles and are not permanent. The effects are reversible, but it will take six months or more for the effects to fade from the body.

Side Effects
Side effects include reduced or absent sexual desire and impotence. Some men also have hot flashes, breast tenderness and growth of breast tissue. Long-term use of these medications also can cause osteoporosis, lowering of the red blood cell count (anemia), muscle atrophy or wasting, and fatigue.

Anti-androgens (Casodex® or Flutamide®)
Even after orchiectomy or during treatment with LHRH analogs, a small amount of androgen is still produced by the adrenal glands. Anti-androgens block the body’s ability to use androgens. Drugs of this type are taken as pills, once or three times a day. Anti-androgens are often used in combination with orchiectomy or LHRH analogs. This combination is called total or combined androgen blockade. A doctor may give an anti-androgen to block the temporary increase in testosterone “flare” with LHRH analogs.

Side Effects
Side effects of anti-androgens in patients already treated by orchiectomy or with LHRH agonists include diarrhea, loss of energy and nausea. Anti-androgens can cause inflammation of the liver. Physicians need to know what medicines their patients are taking with anti-androgens and will check liver function tests.

Intermittent Hormonal Therapy
All prostate cancer treated with hormonal therapy eventually becomes resistant to this treatment over a period of months or years. Some physicians believe that constant exposure to hormonal drugs might promote resistance, and recommend intermittent treatment with these drugs. There is currently a clinical research study to evaluate which method is more effective. With intermittent therapy, hormonal agents are discontinued when a man’s PSA drops to a low level and remains stable. If the PSA begins to rise, the drugs are restarted. One advantage of intermittent treatment is that the side effects of hormonal therapy are potentially minimized.

Chemotherapy
Chemotherapy destroys cells by inhibiting and interfering with the quantity of cancer cells. The role of chemotherapy is evolving as newer medicines are being developed. Traditionally, chemotherapy is used for patients who have prostate cancer cells that have spread and after hormonal therapy has failed. However, chemotherapy is being evaluated in research settings for earlier-stage disease to see if it can be effective for patients at high risk for spread outside the prostate.

Side Effects
The side effects of chemotherapy depend on the type of drugs used, the amount taken and the length of treatment. Temporary side effects include nausea, vomiting, loss of appetite, loss of hair and mouth sores. Because chemotherapy inhibits the bone marrow, patients may have low blood cell counts. This can result in an increased chance of infection, bleeding, bruising and fatigue. Most side effects disappear once treatment is stopped.