Hormonal therapy tries to slow down the prostate cancer cells from increasing by cutting off the supply of male hormones (androgens) such as testosterone that encourage prostate cancer growth. Testosterone primary purpose is to control the development of the sexual organs, including the prostate gland, and many male characteristics such as a deeper voice or muscle strength. Reduction of testosterone production in the body can be achieved by surgery to remove the testicles (the main source of testosterone) or by drugs. Most of the testosterone in your body (90-95 per cent) is produced by the testicles and a small amount comes from the adrenal glands, which sit above your kidneys.
Hormonal therapy focuses on cancer cells which have spread beyond the prostate gland and is thus beyond the reach of local treatments such as surgery or radiation therapy. Hormonal therapy is also helpful in alleviating the painful and distressing symptoms of advanced disease. Further, it is being investigated as a way to stop cancer before it has a chance to metastasize. Although hormonal therapy cannot cure, it will usually shrink or halt the advance of disease, often for years.
Surgery to remove the testicles (orchiectomy or surgical castration) is usually an outpatient procedure. The testicles are removed through a small incision in the scrotum; the scrotum itself is left intact. To help offset the operation’s psychological toll, some men opt for reconstructive surgery in which the surgeon replaces the testicles with prostheses shaped like testicles. Orchiectomies are seldom performed anymore, in most countries.
A variety of hormonal drugs can produce a medical castration by cutting off supplies of male hormones. Female hormones (estrogens) block the release and activity of testosterone. Anti-androgens block the activity of any androgens circulating in the blood. Still another type of hormone, taken as periodic injections, prevents the brain from signaling the testicles to produce androgens.
Possible problems
Either surgical castration (orchiectomy) or medical castration (hormonal drug therapy) can produce a striking response. Both approaches cause tumors and lymph nodes to shrink and PSA levels to fall. However, both castration methods can cause hot flashes, impotence, and a loss of interest in sex. Medical castration by treatment with hormonal drug therapy can cause breast enlargement and can increase a man’s risk of cardiovascular problems, including heart attacks and strokes.
Hormonal therapy has been tried in many different ways. One approach, known as maximum androgen blockade or complete hormonal therapy, combines castration (either surgical or medical) with an anti-androgen pill, taken daily, for months or years. However, studies show that single hormone treatments have similar effectiveness compared to maximum androgen blockade. Combining surgery with hormonal therapy appears to relieve symptoms.
Medical castration by hormonal therapy can be costly, but, unlike surgical castration, its effects can be reversed by stopping the drug. Moreover, halting hormone treatments will sometimes, paradoxically, temporarily interrupt the progress of an advanced and advancing cancer. Some men may benefit from radiotherapy alongside the standard hormone treatment, depending on the stage of their cancer.
Unfortunately, hormonal therapy for metastatic disease works only for a limited time. Remissions typically last 2 to 3 years. Eventually, cancer cells that don’t need testosterone begin to flourish, and cancer growth resumes. When that happens, a variety of other, second-line hormonal-type drugs (for example, hydrocortisone or progesterone) may be tried. There is hope around this problem, too, as some doctors are learning how to make hormone therapy effective longer than 2 to 3 years. Ask your doctor if s/he is familiar with this.
Early hormonal therapy
Early or neoadjuvant hormonal therapy is started as soon as prostate cancer is diagnosed, in hopes of slowing the growth of cancer that has spread into nearby tissues or of cancer that has invaded the lymph nodes. Given prior to surgery, neoadjuvant hormonal therapy often helps to shrink a tumor.
Hormonal therapy is being utilized much earlier in treating prostate cancer than in the past. Work done many years ago by Dr. Fernand LaBrie showed that a combination of two anti-androgenic agents was more effective than any single agent available at that time. This work had been expanded and a number of trials have shown an improvement in disease free and overall survival when an LHRH-Agonist (an injection to deplete the body of testicular male hormone) and an anti-androgen (a pill or pills which block the rest of the male hormone in the prostate cancer cell that is produced by the adrenal gland) are combined. This was first shown to be effective in advanced disease, and now more and more studies are showing that combined hormonal therapy (CHT), when utilized early on, is helpful in better controlling early stage cancer. A number of studies are currently ongoing, showing that patients who receive three months of CHT prior to radical prostatectomy show that about one-third more men have negative surgical margins, compared to patients who go directly to radical, without any hormonal therapy.
At this time, there does not appear to be a difference in recurrence rates at 5 years when PSA is used to indicate recurrence. One of the main criticisms of these studies is that the time these patients were on hormones may have been too short to show a benefit. It will be several years before we know whether or not there is a survival advantage for the hormonal group. Other studies have been done utilizing hormonal therapy before, during and after external beam radiation therapy, and those studies have, thus far, shown an improvement in progression free survival and survival as well in some of the studies.
However, since radical prostatectomies have been done after even six to eight months of hormonal therapy and the vast majority of patients still have prostatic cancer, hormonal therapy is, in my opinion, not sufficient in and of itself.
Metastatic prostate cancer may be either symptomatic or not. The best treatment at present is CHT. It has been clearly shown that CHT improves progression free survival. Patients with metastatic disease who are asymptomatic must consider whether to begin CHT immediately or delay it. A good way to understand these two options is by looking at the data from the NCI Intergroup Trial, which randomized patients with minimal metastatic disease to monotherapy versus CHT. Results show that survival time appears to be much greater with CHT. Furthermore. The survival rate was much greater for the men with widespread metastatic disease using CHT. These two observations and other studies confirming the benefits of the early utilization of hormonal therapy, lead us to conclude that early treatment with CHT in patients with minimal metastatic disease will improve their survival time, compared to waiting until symptomatic metastasis occurs. In fact, there is now a trend in the oncologic and urologic communities to treat patients earlier, before symptoms develop.
See HORMONE TREATMENT and HORMONE THERAPY RISKS
