Cancer-Metastatic prostate

METASTATIC PROSTATE CANCER

Most prostate cancers are stimulated by male hormones, or androgens. Over 95% of the male hormones are produced by the testicles, which send them circulating into the blood stream. The adrenal glands (located above the kidneys) produce the other 5% of the circulating androgens. Treatment for prostate cancer that has spread from the prostate to distant sites (become metastatic) aims to reduce or remove the effect of these male hormones on the cancer cells. Because this can be accomplished in several different ways, physicians don't agree on which is most effective. I am basing my recommendation for you on a number of factors--the amount, location, and histologic appearance (grade) of your cancer, on one hand, and your age and general physical condition on the other. As your physician, however, I want you to understand the treatment options available to you and the reason for my recommendation, because ultimately the final decision will be up to you, the patient.

What is the best way to reduce the effect of the androgens on your prostate cancer if it has spread from the prostate to distant sites? The answer is not clear cut and therefore is controversial. When a patient has no symptoms, some physicians prefer to withhold any treatment--unless and until symptoms develop; others suggest eliminating only the androgens produced by the testicles; still others recommend eliminating all male hormones, those produced by the adrenal glands as well as the testicles. To help you under- stand the reasons behind these options and therefore to make a rational decision about your own treatment, I offer the following background.

Prostate cancer usually metastasizes first to lymph nodes and bones; later it may also involve other organs such as the liver and lungs. The initial treatment for patients with metastatic prostate cancer is directed at lowering the amount of androgens circulating through the blood stream. The basis for this approach goes back to 1940, when Dr. Charles Huggins, working at the University of Chicago, showed for the first time that the prostate is influenced by hormones. The following year he demonstrated that many cases of prostate cancer are likewise under hormonal influence, and patients with metastatic prostate cancer were dramatically improved by surgically removing their testicles (called orchiectomy, or sometimes surgical castration) .This operation eliminated their bone pain and reduced the level of tumor markers in their blood.

For many years thereafter, patients with metastases were treated by orchiectomy, oral estrogens (a female hormone that counteracts the action of androgen), or both. We learned, however, that unfortunately 20% of patients receiving oral estrogens developed a major cardiovascular complication (heart attack, stroke, pulmonary emboli, or phlebitis) during the first 12 months of therapy; as a result, oral estrogens are rarely used. Today we can achieve essentially the same effect using other drugs, called LH-RH agonists (Lupron Depot or Zolodex) , which are not toxic to the cardiovascular system. These drugs, however, need to be administered by a physician every 28 to 30 days.

The immediate results after eliminating testicular androgens from the blood have been good--80% of patients show improvement in their symptoms and in their blood test. The long-range results, however, are not good enough; only one patient in five (20%) is still alive after 5 years, and the median length of survival ranges from 24 to 30 months (2 to 21/2 years).

We have known for many years that androgens are produced not only in the testicles but also in the adrenal glands. Because the adrenal glands produce only about 10% of the total circulating androgens, their activity, until recently, has been considered unimportant. During the last decade, however, studies have shown that after orchiectomy has eliminated the circulating testicular androgens, a 40% concentration of male hormones still remains within prostate cancer cells. It seems, therefore, that adrenal androgens do make an important contribution, at least at the cellular level.

In the early 1980s additional drugs (antiandrogens) were developed, capable of blocking the effect of adrenal androgens in the prostate cancer cell. Dr. Fernand Labrie in Montreal reported longer survival times for patients treated with combination therapy consisting of testicular androgen elimination--by either orchiectomy or an LH-RH agonist--and adrenal androgen elimination using one of these new antiandrogens. As a result of Dr. Labrie's research, the National Cancer Institute (NCI) conducted a large-scale prospective randomized clinical study in 1985 and 1986. This study demonstrated that patients receiving this combination treatment showed significant improvement--in both progression-free survival time and overall survival time--over patients treated by eliminating only testicular androgens.

Since 1987, three additional large-scale clinical studies conducted in Canada and Europe have confirmed these results. In each of these studies, those patients receiving maximum androgen ablation (eliminating both testicular and adrenal androgens) survived 71/2 months longer than those treated only by eliminating testicular androgens. Closer scrutiny of the results from the NCI study performed in this country showed that at least those patients whose disease was less severe (confined to the vertebrae and/or pelvic bones) had a median survival of 61 months (over 5 years), whereas those whose treatment eliminated only testicular androgens survived a median of 41.5 months (31/2 years). Patients with more extensive disease fared less well, but those receiving maximum androgen ablation again survived longer than those whose testicular androgen alone was suppressed (35 months versus 27 months). In spite of these findings, however, many American physicians have not been convinced that this combination drug approach is beneficial and are hesitant to use an antiandrogen. I, however, believe that combination therapy would be preferable and recommend that you consider it.

Finally, in considering treatment options, it's important for you to realize that the results of clinical investigations, especially those conducted by the Veterans Administration Hospitals (VACURG) between 1966 and 1972, suggested that, if the metastatic cancer was not producing symptoms, the patient might do as well by postponing any immediate treatment as by undergoing immediate hormonal ablation. Further analysis of the VACURG results, however, actually provides data in support of early androgen elimination. In addition, a large body of clinical data is beginning to show considerable benefit for early hormonal therapy. I, therefore, believe that immediate therapy will allow you a longer time before you develop symptoms and that you may also live longer as a result of early treatment. You need to be aware, though, that some earlier studies suggested that this may not be the case.

I know that all this information is confusing. It is unfortunate, but true, that the most effective treatment for metastatic prostate cancer is not yet determined. At the present time there is no cure for metastatic prostate cancer, but hormonal therapy will slow the growth and further spread of the cancer and help control symptoms.

I hope this information has been helpful. Remember, I am here to help you understand your own disease, the various treatment options, and why treatment is controversial. I am happy to answer your questions and help you sort out the facts so that, ultimately, you'll be prepared to make a rational decision about what treatment is right for you.