Question 1: What is hormone-refractory prostate cancer (HRPC)?
Men most commonly are considered to have hormone-refractory prostate cancer when their prostate specific antigen level, or PSA, starts to rise while on hormone therapy (also called androgen deprivation therapy [ADT] or luteinizing hormone-releasing hormone therapy [LHRH]). However, a small number of men are diagnosed with an advanced stage of prostate cancer prior to receiving any treatment. They are offered ADT the moment the physician finds prostate cancer well beyond the prostate—for example, in the bones.
Over the years, several names have been given to the advanced cancer condition involving a rising PSA after hormone therapy, but in reality all of the names represent somewhat similar stages of prostate cancer. You may hear any of the terms below used:
Androgen-Independent Prostate Cancer (AIPC) The cancer no longer depends on the androgen receptor or androgen signaling for growth and survival.
Castrate-Resistant Prostate Cancer (CRPC) The cancer continues to grow and progress even though a man has only castrate levels of testosterone or male hormone (less than 50 ng/dL [1.7 nmol/L]).
Hormone-Refractory Prostate Cancer (HRPC) The cancer no longer responds to hormone therapy (LHRH, for example). For simplicity, we will use HRPC throughout this book.
Question 2: How did my cancer become “hormone-refractory”?
Unfortunately, despite hormone therapy, some prostate cancers continue to progress, and more treatment is needed. Those treatments might include options such as second- and third-line hormone therapies, chemotherapy, or, perhaps, even an immune therapy approved by the FDA.
So what actually happens when prostate cancer that responded to ADT turns into HRPC? Why does this occur? Several things can bring about this change:
• There may be increases in the expression of a gene that can keep the tumor alive (known as up-regulation of survival genes), or an increase in the amount (amplification) or the appearance of different types (mutations) of the androgen receptors expressed by the tumor. As a result, the tumor can survive on less testosterone.
• Other unique compounds are activated, accepted, or even produced by the tumor to keep the cancer alive.
• The tumor acquires the ability to create its own concentration of testosterone, bypassing the ADT treatment.
• The cancer alters the body’s control panels and acquires the ability to “feed” itself, so to speak, by creating a blood supply directly into the tumor (a process called angiogenesis). In this process, the tumor may become resistant to specific drugs or even use these drugs as its own fuel.
• The cancer becomes able to evade the body’s immune system and the body no longer recognizes that it has a tumor growing. The tumor can do this by causing changes that keep the immune cells in an immature state, allowing the tumor to move throughout the body without detection.
HRPC patients wage a battle against regular adaptations to the tumor that may occur during the course of treatment. The tumor’s ability to use all or some of these adaptations is what has made it challenging to develop effective treatments for this stage of the disease. Researchers are always working to stay one step ahead of this sequence of events. In the following chapters, we’ll focus much more on treatment options. However, the good news is that more effective treatment options are available now.
Question 3: Should I continue ADT or hormone deprivation treatment going forward?
ADT or hormone therapy works by shutting off most of the testosterone production in the testicles, either through the use of drug treatments or by surgically removing the testicles. Since testosterone has a role in tumor growth, removing testosterone can slow or stop the tumor growth in many cases. Let’s consider for a moment how that process works.
Most prostate cancers have an androgen receptor (AR), a place where testosterone is accepted or recognized by the tumor so that it can grow. One primary way to contain the tumor is by simply removing the testosterone that can fit the AR. It is well established that the growth and survival of prostate tumors, at least for a certain period of time, are dependent on the continued stimulation of the androgen receptor by testosterone. This is why ADT, which eliminates testosterone, has been one of the most successful treatments for more than twenty years.
The initial goal with ADT is to reach castrate levels of testosterone, or less than 50 ng/dL (1.7 nmol/L). However, some experts believe the desired level should be less than 20 ng/dL (0.7 nmol/L). ADT is one of the primary treatments against metastatic prostate cancer and is used along with radiation for more aggressive (high-risk) or locally advanced prostate cancer (cancer that has gone beyond the prostate). Unfortunately, when patients have metastatic disease, the primary response to ADT alone can be temporary. Some men respond for years and years, and others respond for a shorter time.
When patients ask about remaining on ADT after the primary response fails, it is worth pointing out that remaining on hormone therapy can increase the chances of living longer. A study has shown an increased and significant survival advantage for men who did remain on hormone therapy despite having a rising PSA. Also, most clinical trials of new drug treatments require patients to stay on hormone therapy if they want to participate in the trial. Lastly, many leading cancer doctors believe that hormone therapy, despite a rising PSA, continues to provide benefits such as immunity-boosting and the continuous killing of hormone-sensitive cells. In summary, it is worth considering three points:
• Research has shown that, even if the PSA is rising, there are still cancer cells that may respond to testosterone produced by the body. ADT can help kill those cells on a regular basis.
• Research also shows that there may be a slight reduction in symptoms and a greater survival benefit if a man stays on ADT.
• Most clinical trials require men to stay on ADT to enroll, so remaining on hormone therapy keeps options open for your treatment.
Question 4: What is my prognosis right now?
Certainly, one of the most common questions after being diagnosed with HRPC relates to how long you can be expected to live with the disease. The answer is that no one really knows for sure. We do know, however, that this is the most optimistic research period for HRPC in history. Just since the writing of this book was first started, the U.S. Food and Drug Administration has approved six new drugs for HRPC, and five have the potential of extending patients’ lives.
Some individuals call advanced prostate cancer “stage 4” cancer. This is both inaccurate and misleading for it implies that there is a lack of options and that your quality and quantity of life will be very poor. In fact, most men at this stage of the disease can still respond very well to a whole range of options currently available, such as secondary hormonal therapies, immune therapy, chemotherapy, or a clinical trial of a promising therapy.
The various factors listed below all play roles in determining how well someone with HRPC will do. Some men have very aggressive HRPC, while other cancers are not as aggressive. Some patients respond very well to treatment, and others do not respond so well. Generally, the following factors are considered in determining a treatment course for a patient. Bear in mind that no single factor is a clear indicator of success or failure. Just because one or more of the factors below may be associated with a worse prognosis does not indicate a shorter life span, but it may mean that discussions with your doctor will involve
