phoenix5 logo This is an archived copy of an original page from The Prostate Cancer InfoLink site that went off-line in February, 2001. It is reproduced at Phoenix5 with the permission of Vox Medica.
More Prostate Cancer Pages at Phoenix5             About this archive

The Prostate Cancer InfoLink

The Management of
Hormone-Refractory Prostate Cancer:
An Overview

Last Revised March 18, 1996
[Note: Treatment may have evolved since this was written. For education only.]

Introduction | Warning to patients | First considerations | Secondary forms of hormonal therapy | Radiation therapy | Suramin therapy | Chemotherapy | Newer experimental approaches


Many women who have breast cancer receive hormonal therapy with an estrogen known as tamoxifen. Tamoxifen can induce a prolonged response (several years), and should it cease to be effective there are then other forms of hormonal therapy which can be initiated and to which prolonged responses are also common. Unfortunately this is not the case in the management of most men with prostate cancer.

This section of The Prostate Cancer InfoLink will attempt to summarize the major options which are currently available to the hormone-refactory prostate cancer patient. It should be recognized that this, like therapy of other stages of prostate cancer, is an situation in which there are multiple avenues of ongoing basic and clinical research. The options which are listed in this section should not be considered to be exclusive. Your physician may well offer you any one of several other therapeutic possibilities (either as a part of a clinical trial or otherwise) which are not mentioned below.

Warning to patients

Regrettably, at this time, no form of hormone-refractory 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.

Regardless of the type of hormonal therapy which the patient has previously received (e.g., orchiectomy, combined hormone therapy, or others), once a patient begins to fail hormone therapy his options are limited. Unfortunately, at the present time, there are no forms of therapy available which can offer prolonged responses to the hormone-refractory prostate cancer patient.

The wise patient will listen carefully to his physician if he wishes to participate in one or more of the many clinical trials which open for enrollment regarding the treatment of hormone-refractory prostate cancer. A wide range of these trials should be properly categorized as pilot trials. This means that the trial is being carried out to see whether there is enough evidence of clinical response in a small number of patients to justify a larger and more elaborate trial. Pilot trials are not usually carried out with great hopes of prolonged clinical responses in the majority of patients, and, because they are often carried out on patients who have exhausted the known effective therapeutic options, it should be understood that there are significant risks involved in such clinical trials.

First considerations

It is generally considered that for the patient who begins to fail hormonal therapy there are two immediate possible opportunities, depending upon the form of therapy he has previously been receiving:

  • For the patient who has received combined hormonal therapy with an LHRH agonist and an antiandrogen or with an orchiectomy and an antiandrogen, there is the option of antiandrogen withdrawal (stopping the antiandrogen). In many patients this action will result in a short-term decrease in PSA level (usually of the order of weeks or months). This so-called "antiandrogen withdrawal effect" is discussed in more detail elsewhere. The precise nature of the response to antiandrogen withdrawal appears to be related to the form of antiandrogen used.

  • For the patient who has received an LHRH agonist (with or without an antiandrogen) to suppress his testosterone level, this primary suppression of testosterone should be maintained. This can be achieved either by maintaining the patient on the LHRH agonist or by giving the patient an orchiectomy.

The patient who has already received an orchiectomy will clearly continue to have a suppressed testosterone level regardless of other forms of therapy which may be considered.

Secondary forms of hormonal therapy

Secondary hormonal therapy has traditionally been used in a variety of attempts to minimize the rising levels of circulating androgens or to block the effects of those androgens on prostate cancer cells and thus limit growth of prostate cancer cells.

The variety of secondary forms of hormonal manipulation is considerable and they have been addressed in detail in a separate section. Currently available classes of secondary hormonal manipulation include:

  • Forms of testicular androgen suppression
  • Forms of adrenal androgen suppression
  • Additional androgen receptor blockade
  • Cellular receptor activation
  • The use of estrogens and progestins.

The Prostate Cancer InfoLink wishes patients to be very clear that secondary forms of hormonal manipulation are generally of limited benefit. To quote from a recent major text:
Responses are primarily subjective in nature, and there is no evidence that any of these therapies increase patient survival or have consistent palliative effects. ... In those patients who are ineligible or unwilling to consider [participating in clinical trials of invetigational agents], a second hormonal intervention is not unreasonable. The choice of therapy is dependent upon numerous factors, including the performance status of the patients, intercurrent illnesses, and prior hormonal therapy. Treatment must be individualized based on these factors, and it must be emphasized to the patient and family that this approach is purely palliative.

[From Smith DC, Bahnson RR, Trump DL. Secondary hormonal manipulation. In Vogelzang NJ, et al., eds, Comprehensive Textbook of Genitourinary Oncology, Williams and Wilkins, Baltimore, MD, 1995; 885-890.]

Radiation therapy

Radiation therapy is used extensively in the management of hormone-refractory prostate cancer in order to help manage pain associated with the growth of bone metastases. There are two basic forms of radiation therapy available to assist patients with such problems:

  • External beam radiation therapy directed to alleviate pain at specific sites of growth of bone metastases (e.g., the spine, the long bones)
  • Injectable radiotherapeutic agents such as strontium-89 (radionuclides) which tend to be absorbed into growing areas of bone (such as bone metastases) and therefore are able to give relief by slowing the growth of bone metastases.

It is not uncommon for these two form of radiation to be used in combination.

Suramin therapy

In the late 1980s it was discovered that a very old pharmaceutical known as suramin had activity in the treatment of patients with hormone-refractory prostate cancer. For the past few years a number of clinical research groups have been attempting to define the precise value of suramin in the treatment of hormone-refractory prostate cancer.

There are significant problems related to the widespread use of suramin, and these problems still have to be resolved. We do not completely understand how it works. If improperly used it has a range of severe potential toxicities. It induces adrenal insufficiency and patients are therefore likely to require permanent glucocorticoid and mineralocorticoid replacement therapy following suramin therapy.


Cytotoxic chemotherapy, one of the commonest forms of therapy for the majority of cancers, has been relatively unsuccessful in the treatment of hormone-refractory prostate cancer. Quite why this is the case we still do not know. However, it probably has something to do with the fact that, by comparison with other cancers, prostate cancer is a very slowly growing disease.

A detailed discussion of cytotoxic chemotherapy in hormone-refractory prostate cancer is available. The basic content of this section includes:

  • Discussion of the use of single chemotherapeutic agents
  • The potential role of combination chemohormonal therapies.

Other forms of treatment for hormone-refractory disease can be learned about in the section on experimental therapies (see below).

Newer experimental approaches

In the past there were a limited range of methods available for attempting to kill metastatic cancer cells. However, the vast increase in our knowledge of molecular biology and biochemistry in the past 20 years has led to a whole series of potential new therapeutic strategies for the management of hormone-refractory prostate cancer.

It is extremely important for patients to recognize, however, that the majority of these new therapeutic stategies are in early experimental stages of their evolution. It is always possible that a piece of outstanding research will lead to a sudden advance in knowledge and, consequently, a sudden evolution in the treatment of hormone-refractory prostate cancer. At the present time, however, The Prostate Cancer InfoLink strongly advises patients to understand that the types of therapy which will be discussed in this section are unlikely to offer major clinical benfits to patients who are already afflicted with hormone-refractory disease. Regrettably, we still have too much to learn about the biology of prostate cancer and how it can be transformed.

The section on emerging and experimental approaches to the treatment of hormone-refractory prostate cancer includes information on

  • Gene therapy
  • Immunotherapeutics
  • Differentiation therapies
  • Induction of apoptosis (programmed cell death)
  • Regulation of cell signalling systems


Where to Begin?    |    Diagnosis    |    Treatment    |    Support    |    Home Page

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.

Go to Phoenix5 Main Menu