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The Treatment of Advanced Disease

Last Revised November 25, 1995
[advances since 1995 may change the information on this page]

What is advanced disease? | Warning to patients | The role of testosterone | How can we stop synthesis of testosterone? | An historical appreciation of treatment for advanced prostate cancer | Current treatment of stage M+ disease: an introduction

What is advanced disease?

Traditionally, advanced prostate cancer was considered to be disease which had metastasized to areas of the body beyond the immediate area of the prostate and surrounding tissues. Its most common symptom was bone pain, which was the symptom causing physicians to seek a truly effective therapy for this form of the disease. The usual identifying tests were phosphatic acid phosphatase tests and bone scans. Today, the definition of "advanced" prostate cancer is open to more question.

In the strictest sense, advanced prostate cancer is defined as stage M+ disease, in which there is clear evidence that metastatic sites of prostate cancer can be clinically identified beyond the pelvic lymph nodes. However, some physicians have argued that we need to rethink this definition. We now have tests which make it possible (albeit not with great accuracy) to identify micrometastatic groups of prostatic cancer cells outside the prostate (stage T4/M0 disease). Such sites are identifiable in patients who might not provide more traditional signs of stage M+ disease for months or years. How to best treat these patients is becoming an issue of intense discussion among specialists. In addition, another group of specialists have argued that any patient with cancer which has escaped from the prostate capsule clearly has "advanced" prostate cancer since it is no longer localized to the prostate. Such a definition of "advanced" prostate cancer encompasses patients with disease stages as low as T3/N0/M0, which have been traditionally defined as "locally advanced".

For the purposes of this discussion, we are going to continue to consider "advanced" prostate cancer to be cancer in which there is any clear indication that cancer has escaped from the prostate such that there are either definitive signs or symptoms of metastatic disease (e.g., visible metastatic sites on a bone scan and/or prostate cancer-related bone pain) or clear indications of metastatic prostate cancer resulting from tests carried out with such prognostic indicators as PSA tests, RTPCR tests, immunoscintigraphy tests, and other developing molecular indicators of disease progression. We will continue to consider that a patient with positive lymph nodes (stage N+ disease) has a form of "locally advanced" disease unless that patient meets one or more of the other criteria for classification as having "advanced" disease.

Warning to patients

Regrettably, at this time, no form of advanced prostate cancer is curable. All the available forms of therapy are palliative, which means that they can be used only to slow the progression of the disease and to relieve symptoms. In recent years, however, there have been major advances in our understanding of the progression of prostate cancer and our abilities to manage this process. It is now relatively common for some people to live for 10 years and more with advanced prostate cancer, and for much of that time they may not even have evident symptoms of the disease. (The longest period which we have heard of a patient surviving with advanced prostate cancer is 26 years. However, this length of survival with advanced disease is most unusual.)

The role of testosterone

The predominant male hormone is known as testosterone. About 90-95% of it is produced in the male testicles, and it is involved in a wide variety of essentially "masculine" characteristics. One of these characteristics is the development and function of the prostate gland. However, humans are unusual because they also have a secondary source of testosterone. The adrenal gland produces a variety of other male hormones which can be converted into testosterone in the body, and conversion of these other male hormones accounts for the other 5-10% of the total amount of testosterone in the average human male.

In prostate cells (and prostate cancer cells) , testosterone is converted to a product known as dihydrotestosterone or DHT. DHT is a chemical which has profound effects on the growth of prostate (and prostate cancer cells). If you take away a man's testosterone-making ability, you take away the source of DHT, and so you take away much of the ability to stimulate the growth of prostate cells. Of course, this also means that, in patients with prostate cancer, you take away much of the ability for the body to make more prostate cancer cells -- so you slow down the development of prostate cancer!

How can we stop synthesis of testosterone?

There are two basic ways in which doctors can stop a man's body from making ("synthesizing") testosterone: by surgical methods and by pharmaceutical methods. We will deal with the most important of these in some detail.

An historical appreciation of the treatment of advanced prostate cancer

There have been great advances in the treatment of advanced prostate cancer over the past 50 years. At least some users of The Prostate Cancer InfoLink may interested in such an historical perspective because it may help them to understand the continuing problems in finding the best method for treatment of this disease.

Current treatment of stage M+ disease: an introduction

The earliest stage of "advanced" prostate cancer is stage T4/M0 disease, in which there are clear indications of metastatic prostate cancer outside the pelvic area, but there are still no symptoms of the disease which are unrelated to urinary function. In stage M1 disease there is clear evidence of metastatic prostate cancer in other major organs (e.g., the skeleton, the kidneys, the liver, and other soft tissues). M1 disease is often associated with bone pain, which is a consequence of the growth of metastatic prostate cancer in the bone, placing pressure on the nerves. These stages of disease would most commonly be discovered by the use of a bone scan or magnetic resonance imaging (MRI). Some physicians will still use the prostatic acid phosphatase or PAP test as a definitive indicator for stage M1 prostate cancer; however, the use of this test is rapidly declining.

Newer techniques such as the RTPCR test, immunoscintigraphy studies, and analysis of free and bound levels of PSA may increase the likelihood of a diagnosis of stage M+ disease. However, they are not sufficient on their own to provide definitive evidence of stage M+ disease.

There are several different schools of thought when it comes to the treatment of stage M+ prostate cancer. Below there is a list of these schools of thought with links to more extensive discussions of the theories and practices which make up each type of therapy.

We wish to emphasize again that there is insufficient evidence to absolutely state that any one of these options is any better than the others. On the other hand, watchful waiting is certainly the least expensive and combined hormonal therapy the most expensive. Many people have noted the fact that cost can have considerable impact on the types of therapy which are available to different men with different types of health care system and health care insurance in different societies.

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The content in this section of the Phoenix 5 site was originally developed by CoMed Communications (a Vox Medica company) as part of The Prostate Cancer InfoLink. It is reproduced here with the permission of Vox Medica.

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