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
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.