Before reading the text below, you may find it helpful to watch a brief video on the management of metastatic prostate cancer. You can then come back to read the full information on this page.
The Management of “Classic” Metastatic Disease
Historically, metastatic prostate cancer (Jewett-Whitmore stage D2, equivalent to TxNxM1 disease) referred to prostate cancer in which there were clear signs of metastatic disease, evident on bone scans of patients. Customarily, the early signs of such disease were metastases to the spine and the pelvis. Later on bone metastases could be seen throughout the patient’s ribcage and long bones too.
Figure 1: Bone scan of a patient with clear signs of prostate cancer
metastasis in the pelvic area and throughout the spine.
Hormone therapy has long been the classic form of treatment for patients with this form of metastatic prostate cancer. Hormone therapy in such patients is not curative. The intent of hormone therapy in such patients was first to delay the onset of the side effects of metastasis to the bones (pain, fractures, and other severe effects on quality of life) and only secondarily to delay the progression of the cancer and increase the patient’s survival — if at all possible.
In the past (only as long ago as the mid 1980s) it was common for patients to be first diagnosed with Jewett-Whitmore stage D2 disease. Their life expectancy, even with hormonal treatment, was relatively short, and many patients would suffer for long periods of time with excruciating bone pain once the hormonal therapy was no longer effective.
This form of prostate cancer, diagnosed as the initial presentation of the disease, is still widespread in developing parts of the world among older males, and even in some of the developed areas. These men do not receive regular PSA tests and, if they survive other forms of disease (AIDS, malaria, cholera, yellow fever, etc.), then prostate cancer is still a significant risk in their old age. If patients diagnosed initially with this stage of prostate cancer are given PSA tests, it is not unusual for them to have PSA levels well over 500 or 1000 ng/mL.
“Modern” Metastatic Prostate Cancer
Today, in America and most of the developed world, an initial diagnosis of evident metastatic prostate cancer would be relatively rare. The vast majority of prostate cancer patients are diagnosed much earlier in the course of their disease as a consequence of PSA testing.
Most patients who are not cured of their disease by treatment when it is still localized to the prostate and/or the surrounding tissues will, over time, progress (some very quickly; some much more slowly) to metastatic disease. However, the course of this metatstatic disease will normally be very different to the classical situation.
In the first place, we will know they have metastatic disease early on, despite prior therapies. However, the initial presentation of metastatic disease will not involve any visible signs of metastasis. The only sign will be a constantly rising PSA that gradually starts to rise beyond (say) 20-30 ng/mL if some form of hormone therapy is not initiated. This form of metastatic disease is defined as stage TxNxM0 disease
The critical and much disputed issue with these patients is when hormone therapy should be started and what form it should take (or indeed whether other forms of investigational therapy should take priority). These patients have what is customarily referred to as micrometastatic disease, where there are tiny tumors starting to form outside the prostate but they are so small that they can’t even be seen on a CT scan or an MRI scan (let alone a bone scan). There is no definitive guidance regarding any of the following:
When such patients should start to receive hormone therapy
What type of therapy to give them, or
Whether their therapy should be continuous or intermittent
Furthermore, with the evidence now available that at least one form of chemotherapy (docetaxel/Taxotere) is effective in the treatment of patients who have failed hormone therapy, there are now clinical trials exploring the earlier use of chemotherapy, either before or in combination with hormone therapy, as treatment for patients with micrometastatic disease.
Basically, the management of metastatic prostate cancer is in a state of major evolution. There are many forms of treatment under investigation, ranging from newer forms of hormone therapy to chemotherapies and immunotherapeutics (the so-called prostate cancer “vaccines”). Within a decade we may have much clearer ideas of what can most effectively be done to prevent the progression of micrometastatic disease. Today, however, it is very much a matter for individual discussion between a patient and his doctor, and a critical question that will drive the decision process is going to be, “Just how fast is your cancer progressing, and how accurately can we tell?”
Types of Hormone Therapy Available
A significant number of options are now available as methods of implementing hormone therapy. However, they all fall into one of the following groups:
- Surgical removal of the testes to prevent synthesis of testosterone at the source (orchiectomy)
- The use of various hormonally active drugs called luteinizing hormone releasing hormone agonists (LHRH agonists) to lower the levels of testosterone in the bloodstream
- The projected future use of luteinizing hormone releasing hormone antagonists (LHRH antagonists) such a degarelix to lower the levels of testosterone in the bloodstream
- The use of “nonsteroidal antiandrogens” to suppress the activity of a male hormone known as dihydrotestosterone (DHT)
- Cessation of antiandrogen therapy, which commonly results in what is known as an “antiandrogen withrawal effect” and a short-term lowering of PSA levels
- The use of a technique known as combined hormonal therapy or maximal androgen deprivation, which combines suppression of testosterone production and suppression of adrenal androgen production
- The use of a technique known as intermittent hormonal therapy, in which hormones are given and then stopped according to a predetermined regimen so that the patient’s testosterone levels are not permanently suppressed.
- The use of other techniques or pharmaceuticals to suppress the biosynthesis of the small proportion of male hormones made by the adrenal gland (adrenal androgens).
Patients who fail first line hormonal therapy may also be appropriate for second line hormonal manipulation prior to chemotherapy.
The critical factors in choosing a particular form of hormone therapy can include the cost of the treatment (and who is paying for it), the effectiveness and safety of the various treatment options, and the effects of the different forms of treatment on the patient’s quality of life. It is common for different forms of hormone therapy to be combined with each other, and it is increasingly common to find hormone therapies and chemotherapies being combined with each other.