TREATMENT OF PROSTATE CANCER WITH HORMONE THERAPY?

The prostate gland is an organ that makes nutrient fluid (seminal fluid) to nourish the sperm. The prostate increases in size with age. As the prostate gland grows, it can cause urinary symptoms of decreased stream, hesitancy, frequency, urgency to void, and frequent urination at night. Islands of the prostate gland can also form cancer cells. The prostate tissue is very sensitive to the male hormone testosterone, causing normal prostate cells and prostate cancer cells to grow.

This observation led urologists to the use of hormone reduction to treat prostate cancer in the 1940s and except for newer drugs, the principle of hormone reduction still stands today. Today the most common ways of effecting male hormone reduction is surgical removal of the testicles (orchiectomy), or shots every 1 to 4 months of Lupron (TAP Pharmaceutical) or Zoladex (AstraZeneca) which cause the testicles to stop producing the male hormone, testosterone.

In patients, where the prostate cancer has spread outside of the gland into other parts of the body such as lymph nodes, bone, lung, or liver, hormone treatments are frequently recommended. When spread of the cancer has occurred, the disease can not usually be cured with surgical removal or with radiation treatments. This is because the cancer is almost always more widespread and all of the cancer cell can not be treated or removed. Since hormone therapy treats the entire body, cancer cells too small to see can be treated, no matter where they are.

Occasionally, patients with localized prostate cancer are treated with hormones as well:

1. One circumstance is where patients, for varied reasons, cannot undergo surgery or radiation immediately and the hormone treatment allows us to delay treatment.
   
2. Another situation is when doctors may wish to shrink the prostate cancer to allow surgery or radiation to possibly be more effective. This is especially true for patients with large glands that may be opting for brachytherapy, or seed implantation. The prostate needs to be less than 50 grams in most cases, and the hormones will shrink the prostate. This process takes about 3-6 months in most cases.
3. Adjuvant therapy is where Lupron or Zoladex is given to help improve the results of standard radiation therapy or surgery.

WAYS TO DECREASE THE MALE HORMONE, TESTOSTERONE:

1. Orchiectomy - The testicles manufacture almost all of the male hormones. Therefore, removal of both testicles lowers the hormone levels sufficiently to often achieve an excellent response against the prostate cancer. The procedure requires a brief anesthetic (general, spinal or local) and usually requires less than 30 minutes to perform. In most instances, the patient goes home from the hospital on the same day. There is some discomfort that is usually treated with a mild pain medication and a few days of restricted activity. A small chance of infection exists, along with the risks associated with the anesthesia.

   The side effects of removal of the testicles are mild in most cases. The most problematic are 'hot flashes'. Because of the abruptness of the hormone changes, some men will have 'hot flashes', which consist of brief episodes of feeling of warmth, sweating and redness, especially of the face. Rarely, these can come so often that we need to offer medication to try to reduce their effects. Usually the flashes decrease with time.

2. Hormonal Injections (Lupron or Zoladex) - These are long-acting medications that are injected into the buttocks or subcutaneously under the skin, These medicines are able to stop the testicle from producing testosterone. The action of the drug is actually on the pituitary gland in the brain, which makes, LH (Leutenizing Hormone), a special hormone that stimulates the testicles to release testosterone. Without LH, the testicle does not make any significant amount of testosterone. The effect is the same as orchiectomy. Testosterone production by the testicles is stopped.

   The injections have no direct effect on the cancer, only an effect on the testicles. The lack of male hormone circulating in the blood kills the prostate cancer cells. The major advantage is no need for surgical removal of the testicles. Most patients prefer the injections instead of having their testicles removed.

   The disadvantages are the need for an injection every 1 to 4 months, but most men are willing to exchange the effort to spare their testicles. There is a high to cost of the medication; however, this treatment is standard and is covered by almost every insurance company, HMO, and by Medicare. Allergic reactions have been reported and can result in a rare case of arthritis.

3. Intermittent Hormone Therapy is currently being investigated. Intermittent hormone therapy is a treatment regimen where hormone therapy is started and when the cancer shrinks to a certain level as measured by the PSA, we stop the hormone therapy. Treatment is re-started when the cancer grows again (as measured by PSA). The advantage of intermittent hormone therapy is a reduction in the side effects of the hormone therapy during the periods that the patient is off treatment and reduced overall costs. Early studies have suggested that success in treating the cancer is not hurt by using intermittent therapy. Intermittent therapy is still investigational.

4. Female Hormones - Until the mid-1980s, female hormones in pill form, particularly Stilbesterol, were used to treat prostate cancer. Female hormones act on the male pituitary gland in the brain to reduce the release of a special pituitary hormone that stimulates the testicles to release testosterone. Female hormones had the advantage of requiring only a daily pill to take, but has the disadvantage of increased risks of heart attack and stroke and also caused painful breast enlargement in many men. We still use female hormones to reduce the effects of hot flashes in some men, and occasionally in men whose tumors have started to grow again despite the hormone treatments.

5. Additional Hormone Therapy - Many studies have suggested that the addition of another type of medicine called anti-androgens, may help potentiate the effectiveness of either hormone injections or removal of the testicles. The most common ones used are called flutamide (Eulexin) or bicalutamide (Casodex). These drugs, taken in pill form, further reduce the hormone levels by blocking the action of remaining male hormones (mostly made in the adrenal glands). Some controversy still exists as to the effectiveness of this additional treatment and the cost is about $300 per month. Many insurance companies pay for this medicine, while other companies, including Medicare do not cover this prescription.

   A certain percentage of men will have some reaction to the medication, particularly diarrhea (more common in flutamide than bicalutamide). The symptoms resolve in time or the dosage can be reduced. At this time, doctors may suggest that flutamide or bicalutamide be used if the cost of the medicine will not be a burden and the side effects are minimal. The usefulness of these medications is still not a certainty to all investigators. So that if you do not use antiandrogens, you shouldn't feel that you are getting inferior or substandard treatment.

1. The cancer has spread to other areas of the body away from the prostate, such as bone, lung, liver, lymph nodes (otherwise known as metastasis or metastatic cancer). The exact time to start treatment varies with each patient. In some patients treatment is started when the diagnosis of metastatic disease is made, in others, we may wait for symptoms, such as pain, before starting treatment. The major advantages of delaying treatment are the lack of side effects from the hormone therapy and the reduced cost. Overall survival time may be improved by starting earlier.

2. As preparation for radical surgery or radiation therapy to cure the cancer. Some studies have shown that hormone therapy can be used to make radical prostate surgery or radiation therapy more successful. The treated cancer shrinks before and during hormone therapy, thereby possibly increasing chances for successful curative therapy. The hormone therapy is stopped after surgery or radiation. This is investigational for now.

   How long is hormone therapy used?
   For patients with metastatic cancer, the therapy is used indefinitely as long as the therapy is successful in controlling or stopping the growth of cancer.

   As preparation for radical surgery, external beam X-radiation, and brachytherapy (seed implantation), the therapy is usually given for three to four months. Surgery is then performed and the medication is stopped.

Summary

Hormone treatments for prostate cancer have been used successfully for over 50 years. The overall success rate or chances of the cancer shrinking is greater than 70%. In those that respond, the length of time that the tumor remains under control is variable, but can be many, many years. Doctors will continue to follow your cancer with examinations, blood tests (particularly PSA) and other scans, depending on your circumstances.

by
by Stephen M. Auerbach, MD
Board Certified Urologist
Medical Director for California Professional Research
HHH education information staff member , HisandHersHealth.com