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ОглавлениеQuestions and Answers to Start
When a patient is confronted with prostate cancer that is advancing, certain important questions come to mind almost immediately. It seemed to make the most sense to put those questions on the table first and provide some general answers before we get into more depth in upcoming chapters.
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 different options appropriate for your individual situation. In other words, knowing that your cancer may be more aggressive can give you a better indication of how aggressively you want to have your cancer treated.
Prognostic Indicators To Discusss with Your Doctor
Age Age has very little impact by itself on whether or not you would qualify for or respond to an HRPC treatment. Overall, older men tend to respond just as well as younger men to HRPC treatment. However, younger men diagnosed with HRPC tend to have a worse prognosis simply because they have more aggressive tumors in some cases. And, since they are expected to have a longer life span, and since fewer currently have other health issues, HRPC does have a greater chance of eventually impacting them. In other words, older men are more likely to also have other serious diseases (co-morbidities, such as heart disease, diabetes, and other cancers) that could affect their lives during the time they are being treated for HRPC.
Albumin This is an important protein in the blood that is measured by a blood test. It serves as a carrier for all sorts of vital substances in the human body. A normal albumin level is a good indicator that the body is doing well when receiving treatment, but an abnormally low albumin level could be an indicator that the patient is not doing as well.
Alkaline Phosphatase A blood test for alkaline phosphatase measures the quantity of an important enzyme in the body that can help to predict the aggressiveness of your HRPC, as well as what the cancer is doing to your body. An abnormally high level of this enzyme tends to suggest that the cancer is being more aggressive and is not responding as well to treatment.
Asymptomatic or Symptomatic There are two distinctly different clinical stages within HRPC, namely, individuals who are asymptomatic (experiencing no symptoms at all) and symptomatic (experiencing some symptoms). Thanks to the PSA test and better imaging tests, the majority of men currently diagnosed with HRPC are asymptomatic. This is because the disease is being detected earlier and earlier, opening up more treatment options for HRPC patients. Men with asymptomatic HRPC have a better prognosis, in general. However, this may change somewhat in the future as more and more drug treatment options for men with symptomatic HRPC are in clinical trials right now.
Bone Metastasis and Number of Bone Metastases In general, individuals with HRPC who have bone metastasis (cancer that has spread to the bone) have a cancer that has progressed further than that of someone with no bone metastasis. Individuals with more bone metastasis could have a worse prognosis or a more serious HRPC, for the cancer has spread to more places in the body. In addition, when cancer spreads to unusual bone sites, such as the skull, new data suggest that such spread is associated with a more aggressive cancer.
Bone-Protecting Medication There is some preliminary indication in other types of advanced cancer that receiving a bone drug to reduce the risk of bone loss after being diagnosed may also reduce the risk of bone metastasis and improve survival. Studies are preliminary, but it appears that protecting your bones after being diagnosed with HRPC is critical to reducing the risk of bone loss that could delay your cancer treatment.
Circulating Tumor Cells The practice of monitoring circulating tumor cells (CTCs) to assess the effectiveness of a treatment or give some indication of prognosis is starting to get some attention. CTCs are epithelial cells that actually come free or are shed from different tumors. These CTCs can be counted in a new blood test (for example, “cell search”; see www.veridex.com). This test is being used in some clinical trials right now, and there seems to be an indication that when a drug causes a reduction in CTCs during treatment, or when there are fewer CTCs before the treatment, there is an increase in survival rates. This makes sense, because a reduction in tumor cells probably means that some cells have been destroyed. Ask your doctor about this new test if you are interested.
Diet, Lifestyle Changes, and Over-The-Counter Medicines Whether or not any diet or supplements could improve your HRPC prognosis specifically has not been proven, but a man who exercises regularly, eats a moderately healthy diet, and maintains a healthy weight may reduce his risk of getting other diseases that can reduce his life expectancy. A recent study of men diagnosed with HRPC found that a large number of men actually die yearly from other causes, such as cardiovascular disease. In the diet and supplement section of the book, you will find heart-healthy tips that may fight prostate cancer and a list of dietary supplements to consider taking or to avoid based on research on their likely effect on prognosis.
Gleason Total Score and Primary Gleason Score A higher total Gleason score (scores of 8 to 10, for example) indicates a more aggressive cancer. Prognosis or response to a drug could be worse for someone with this type of tumor as compared with someone who has a moderate or low Gleason score (below 8, for example). Most Gleason scores on tumors were established a long time ago for men with more localized disease, but knowing this number is still helpful in making treatment decisions. Some researchers believe that the first number in your Gleason score, called the primary Gleason score, is as important as the total Gleason score. For example, a primary Gleason score of 4 or 5 suggests a worse prognosis as compared to a primary score of 3. A man with a Gleason total score of 5 + 3 = 8 may have a worse prognosis as compared to someone with a score of 4 + 4 = 8.
Hemoglobin A hemoglobin count is a measure of the oxygen-carrying protein in your red blood cells. If hemoglobin is very low (a situation called anemia), a person may feel tired, and it will be more difficult for him to receive treatment. It is not unusual to be slightly anemic due to testosterone-lowering treatments, but an abnormally low hemoglobin level that causes a variety of symptoms (fatigue, breathing problems, etc.) may need to be treated. It can make the prognosis slightly worse by causing a delay in cancer treatments.
Hormone Treatment (LHRH, ADT, or Surgical Castration) As we discussed earlier, maintaining a castrate level of testosterone is recommended for most HRPC patients. This may provide both quality- and quantity-of-life benefits. But is it better to reduce testosterone by using regular LHRH injections, or just to have the testicles surgically removed? There has been no strong research to show that there is a survival or prognostic advantage of one method over the other. However, in some surveys of patients there seems to be a quality-of-life benefit for those who receive regular LHRH injections. Patients visit their doctors frequently to receive the injection, and that may be a positive thing. The injection may provide the patient with a feeling of control over the process and allow him to avoid surgery to permanently remove the testicles. It is worth noting that most patients who take LHRH injections for a period of time will not start to produce testosterone again, even if the injections are stopped. A patient who has to travel long distances to receive the injections may benefit from surgery.
Imaging Test Results X-rays, bone scans, CT scans, MRIs, or any other imaging tests that show that the cancer is spreading to more body sites tend to indicate that the cancer is more aggressive and not responding to treatment. Cancer that is not spreading or tumors that are shrinking in size are both good indicators that the patient is responding to treatment. (More information on imaging tests can be found at the end of this chapter.)
Lactate Dehydrogenase Also known as LDH, this is an important enzyme in the body that can be measured in a blood test and can help to predict the aggressiveness of your HRPC or what the cancer will do to your body. An abnormally high level of this enzyme tends to suggest that the cancer is more aggressive and is not responding as well to treatment.
Medical History and Co-morbidities It makes sense that your general health and any other diagnosed diseases (co-morbidities) can have an impact on your prognosis. Not surprisingly, individuals with other serious disease besides prostate cancer have a greater chance of dying younger. Individuals who are healthier in general and who have few to no co-morbidities tend to live longer. For example, obesity does not seem to impact HRPC prognosis, but it does increase the risk of dying younger from other causes, such as cardiovascular disease. Keeping other disease states under control, as much as possible, and maintaining general health through exercise and proper diet make a lot of sense.
Pain Men with HRPC and different pain levels tend to have different prognoses. The worse the pain caused by the cancer itself, the worse the prognosis or the more serious the situation. This makes sense because tumors that have grown large enough to cause pain are more troubling than smaller tumors not causing pain. Pain caused by other chronic conditions, such as arthritis, does not play a role in this consideration.
Performance Status Performance status is a scale that attempts to quantify the general well-being or quality of life of a patient. Healthcare professionals use the scale to determine whether someone should receive chemotherapy treatment, whether a dosage change is needed, or if therapy should even be continued for a particular patient. Two commonly used scales are the ECOG (Eastern Cooperative Oncology Group, one of the largest clinical cancer research organizations in the United States) test and the Karnofsky Performance Status test (named for Dr. David A. Karnofsky). A brief description of each follows. Overall, a poor performance status indicates a worse prognosis as compared to someone with a better performance status.
ECOG Performance Status
Numerous clinical trials require an ECOG performance status of 0 to 2 in order to be allowed to participate in clinical trials. Scores of 3 or 4 usually do not receive chemotherapy because the possibility of benefit is outweighed by the potential of negative side effects (of course, there are exceptions).
0 Asymptomatic (fully active, no restrictions)
1 Symptomatic and fully able to walk (can perform light work, such as household or office tasks, but cannot do strenuous activity)
2 Symptomatic and spends less than 50 percent of time in bed (can walk and provide self-care, but unable to do work activities)
3 Symptomatic and spends more than 50 percent of time in bed or chair (not bedbound, capable of limited self-care)
4 Bedbound (cannot provide for self-care, completely confined to bed or chair)
Karnofsky Performance Status
Can be expressed as a range (90–100) or a specific number (92).
100 Normal, no complaints or signs of disease
90 Normal activity, few symptoms or signs of disease
80 Normal activity, some symptoms or signs of disease
70 Caring for self, not capable of normal activity or work
60 Needs some help, can take care of personal requirements
50 Needs help often, requires frequent medical care
40 Disabled, needs special help and care
30 Severely disabled, hospital admission indicated but no danger of death
20 Very ill, urgently needing admission, needs supportive measures of treatment
10 Rapidly progressive
Previous Response To Treatment(s) Response to previous HRPC treatments is a good indicator of prognosis or the aggressiveness of your tumor. For example, someone who responded well to several cycles of Taxotere chemotherapy has a better prognosis as compared to someone who responded for a short time or not at all. A patient who had a positive PSA response to several anti-androgens or secondary hormonal therapies has a better prognosis in general than someone who did not respond to any of them. Positive response to one drug treatment for HRPC is a good indicator that this same individual could respond favorably to other treatments.
Primary Tumor Site Status or Debulking This is a very controversial prognostic indicator. A number of opinions exist, and there are no clear answers as of this time, but it is a topic you may want to discuss with your doctor. In some other tumor types, such as colon and ovarian, a person with advanced cancer may have a better prognosis when the primary tumor or the location where the tumor initially began to grow is removed (debulked). It appears that removing the ovaries or part of the colon even though a patient has cancer that has spread far beyond these areas could still provide a benefit. How? Simply removing part of the primary tumor may make it less able to send out more cancer cells into the rest of the body or even communicate with other tumor cells in the body. Does this mean that men with HRPC should get their prostate removed or get radiation to the prostate again? While there is no definitive answer at this time, it may be worth discussing with your doctor.
Prostatic Acid Phosphatase (PAP) Historically, this blood test was used before the PSA test was invented to determine whether someone had prostate cancer. However, the prostatic acid phosphatase (PAP) number only increased to large values when the disease had already spread to different areas of the body, making early detection difficult. Some doctors still use this test once in a while to determine if HRPC is more extensive when they cannot find any tumors on the imaging devices. While this test may complement the prognostic value of the PSA in some rare situations, it does not tell the doctor more than what the other tests are showing for most patients.
PSA and PSA Kinetics Increasing PSA, rapidly increasing PSA, or a PSA that does not respond to a treatment could all be indicators of a worse prognosis, but keep in mind that there are exceptions to this rule. For example, Provenge treatment for HRPC does not necessarily reduce PSA levels, but it is associated with a greater survival rate. On the other hand, Taxotere chemotherapy tends to lower PSA or slow the rise in PSA in many men, and it is also associated with an improved survival for HRPC. There are also cases where very aggressive tumors don’t produce PSA, and where less aggressive tumors create a higher PSA. Considering both your PSA before treatment and location of the tumor in the body may provide some guidance.
PSA kinetics (doubling time, velocity) may also be useful. For example, the longer it takes for PSA to double after treatment, the more likely it is to be a favorable prognostic sign.
Race and Ethnicity may have an impact on prognosis for many reasons. Past studies have indicated that non-Caucasian men or minorities tend to have less access to healthcare or are more likely to have their treatment delayed. Improved education and healthcare access may resolve this factor in the future.
Staging of Cancer Staging is a system used to identify where a cancer is located and how far it has spread. The TNM staging system is the most common one used for prostate cancer. The acronym stands for primary tumor location (T), lymph nodes (N), and metastases (M). The tumor location is based on the results of a clinical examination, imaging tests, a biopsy, and blood tests. The node assessment is generally based on a clinical examination, imaging, or lymph node removal. The assessment of metastases utilizes clinical examination, imaging, specific bone or skeletal studies, and blood tests. Every prostate cancer should be given a T, N, and M assessment. An “x” or “0” score for the T, N, or M indicator usually means that either the location of the tumor cannot be determined currently (for example, Tx, Nx, or Mx), or there is no evidence of cancer in that area after evaluation (for example, T0, N0, or M0). Subcategories can be used to provide a more exact tumor location, but those subcategories won’t be covered here because in treating hormone-refractory cancer patients more emphasis is placed on the N and M staging. Not surprisingly, patients with a higher TNM stage have a worse prognosis than patients with a low TNM stage.
Testosterone Levels There is some preliminary research to suggest that a patient who had an abnormally low testosterone level before receiving an LHRH medication or surgical removal of the testicles could have a more aggressive prostate cancer, and that it may be more difficult to treat. This is preliminary, but it does make some sense that such a cancer would be able to grow with less testosterone available, making LHRH medication possibly less effective. In other words, some of these cells may have found a way to survive without much testosterone.
Time from Initial Treatment to CRPC Diagnosis If you were treated for localized prostate cancer, and then it rapidly progressed to become HRPC, this could indicate a more aggressive cancer. However, if you were diagnosed and treated for localized prostate cancer, and many years later the disease came back, and several years after that it became HRPC, it would imply a slow, steady cancer that may have a better prognosis.
PELVIC NODES
The pelvic lymph nodes are the first set of nodes in the human body where prostate cancer usually goes after growing beyond the prostate area.
Visceral Disease or Soft-Tissue Disease The literal meaning of visceral is “of the internal organs,” and this has come to mean cancer that has spread to locations apart from the prostate or bones, such as the liver, lungs, or other areas far from the prostate. Individuals who have visceral disease or cancer in multiple areas of the body and around the prostate tend to have a worse prognosis than those without disease in these areas. This is because the disease has advanced further. The situation is similar with what is called “soft-tissue disease,” where the cancer has gone to non-bony areas such as organs and/or regional or non-regional lymph nodes.
ABDOMINAL NODES
The abdominal pelvic lymph nodes are the second set of nodes where cancer may typically spread.
Volume or Amount of Cancer In general, the greater the amount of cancer in your body, the more aggressive the tumor, and the more serious the situation. For example, someone with cancer in the lymph nodes, in some organs, and in many bones tends to have a more aggressive cancer as compared to someone with just a few tumors located on a single bone. This is why working with your doctor to find the location of your tumor sites as early as possible is an important tool in planning treatment.
PERI HILAR/SUPRACLAVICULAR NODES
The Peri Hilar/Supraclavicular lymph nodes, located generally speaking in the chest and neck area, are usually the third set of nodes where prostate cancer spreads.
Weight Loss When the cancer itself is impacting a variety of areas of the body and causing extreme weight loss, this usually means that the cancer has become more aggressive and occupies more of the body as compared to someone without weight loss. In general, when men have castrate levels of testosterone because of LHRH treatment or surgery, there is usually some weight gain, or it is at least difficult to lose a lot of weight, even with exercise and diet. Therefore, when a patient begins to lose weight, this is often associated with a worse prognosis. Exceptions include when a chemotherapy drug causes nausea, resulting in weight loss due to a lack of appetite and not because the cancer is progressing. Weight loss due to cancer spread is more troubling.
Question 5: What treatments are available for my HRPC right now?
Many options currently exist, including:
• Anti-androgen addition or withdrawal
• Secondary hormonal therapies
• FDA-approved therapies
• “Off-Label” use of a drug already approved for a different type of cancer
• Enrolling in a phase-1, -2, -3, or -4 research study
• Find a drug in a phase-3 clinical trial that is available for an Early/Expanded Access Program (EAP) or Compassionate Use Program
As this book was being written, it became apparent that we would need to do a quick review of the process that drugs go through before they are readily available for use on patients. After some initial laboratory testing, it may be determined that a drug is ready for human testing. Before it receives a final approval from the FDA, it will go through several phases of testing. In the following section you’ll find more information on what happens in each phase of testing and who is eligible to participate. In considering any trials, first check to see if you will be required to pay for anything for the trial. One advantage of being in such a trial, in addition to receiving a potentially exciting new treatment and contributing to research knowledge that could help you and others, is that there should be little to no cost for you. Patients also participate in clinical trials to try therapies for which they do not technically qualify under FDA guidelines. For example, a patient who does not have metastatic disease may join a trial for a drug only FDA-approved for metastatic patients thus far. Here, quickly, are the differences among phase-1, -2, -3, and -4 trials:
Phase-1 Clinical Trial
Who are the best candidates? Individuals with limited, minimal, or no treatment options.
Description:
• Generally enroll fewer than 100 patients.
• May test different types of cancers or a single type of cancer.
• Enroll a small number of participants to generally determine how a new treatment should be delivered in terms of the most effective maximum dosage, safest dosage, how often the drug should be given, and in what form the drug should be given (IV, pill, injection, patch, gel). It is not unusual for a new drug to be tested at several doses, monitoring efficacy and all side effects.
What is the catch? Drugs that have not gone beyond phase-1 testing still have many years of testing before they may be approved. The exception to this rule is a drug being tested in phase 1 that is already approved for another cancer. It then is possible to get it off-label, meaning you may have access to this drug immediately if you qualify (for financial reasons, clinical reasons, specific doctor choice, etc.), so you do not need to be in a clinical trial.
Phase-2 Clinical Trial
Who are the best candidates? Individuals who have minimal to moderate options, but who want to test a new and exciting emerging treatment.
Description:
• May enroll fewer than 100 to several hundred patients.
• Enroll a higher number of patients to begin to test the safety and efficacy of a specific dosage.
• These trials usually enroll participants with a specific type of cancer and generally test against the standard of care for an experimental treatment.
What is the catch? Drugs that have not gone beyond phase-2 testing still have several years of testing before they may be approved. The exception to this rule is a drug being tested in phase 2 that is already approved for another cancer. It then is possible to get it off-label, meaning you may have access to this drug immediately if you qualify (for financial reasons, clinical reasons, specific doctor choice, etc.), so you do not need to be in a clinical trial.
Phase-3 Clinical Trial
Who are the best candidates? All types of HRPC patients may qualify because they should (make sure you check) get the standard currently available approved treatment or one of the most promising treatments available (but not approved), involving a drug that has already done so well in phase-1 and -2 testing that it is ready to be tested in phase 3.
Description:
• Determines whether or not the promising drug will get FDA approval.
• Generally enrolls hundreds to over a thousand patients at many different locations.
• A participant is randomly assigned to the current approved treatment or the new potential treatment (a process called randomization). In other words, every participant gets the standard-of-care/approved treatment for this condition, or else gets the new and emerging potential treatment.
• “Crossover” is also usually available in a phase-3 trial. This means if you stop responding to the treatment that you are initially assigned (either the standard of care or potential drug), then you will be allowed to get the other treatment in the trial if you want it. Ask about this possibility in any clinical trial.
What is the catch? Drugs that have not completed phase-3 testing still have at least one to a few more years to be tested before they can get approved. The exception to this rule is a drug being tested in phase 3 that is already approved for another cancer. It then is possible to get it off-label, meaning you may have access to this drug immediately if you qualify (financial reasons, clinical reasons, specific doctor choice, etc.), so you do not need to be in a clinical trial.
Phase-4 Clinical Trial
Who are the best candidates? All type of HRPC patients who qualify because they should receive an approved treatment for HRPC.
Description: Involves further testing of a treatment after it has been approved in order to further investigate how best to continue to use this treatment.
What is the catch? Drugs that have completed successful phase-3 testing and are entering phase-4 testing have been approved, so why enter a clinical trial for a drug that is already available and probably covered by insurance? A few possible reasons are that the drug may be provided at a lower cost to you in terms of out-of-pocket expense, or that you may want to continue to support research and knowledge on an available drug, or because the new protocol with the drug being tested is one that may have a better response potential as compared to the standard of care. There are some phase-4 tests that involve getting more frequent treatments or more potentially potent dosages, and for someone with more aggressive HRPC this may be an attractive option.
Question 6: What is “early/expanded access” or “compassionate use,” and why is it important to some men with HRPC?
Answer: Individuals with few or no remaining treatment options or those who are no longer responding to any of the currently available treatment options for HRPC may be given access to phase-3 drugs at little to no cost. Efforts are currently underway to expand the number of drugs available to patients through this valuable program. Always be sure to ask to see if a drug is available for an interesting new treatment if you have limited options or do not qualify for the study. The potential downside is that just because a drug becomes available for EAP or Compassionate Use does not mean that it will be effective.
IMAGING TESTS USED IN PROSTATE CANCER
A variety of imaging tests are used to give physicians a reliable analysis of the location and possible spread of your cancer. Many of these tests are used to provide a baseline when compared to the same test at a later date. For example, comparing a recent bone scan to a bone scan from months or years ago can help determine if bone metastasis or further spread of the cancer has occurred. These tests may lead to further tests or treatments, such as a biopsy, the removal of a lymph node, or the treatment of an area of the body to eliminate tumor cells. Most of these imaging procedures are painless, with the possible exception of a needle stick to inject dye to improve readability of results.
Bone Scan
Advantage A bone scan, also called a “radionuclide bone scan” or “bone scintigraphy,” is the gold standard test for determining if a patient has prostate cancer that has spread to any of the bones.
The catch The test exposes the patient to radiation and may not be able to pick up very tiny bone metastasis. It can appear falsely positive for cancer if the patient has arthritis, degenerative bone disease, infection, or fracture.
Computed Tomography (CT scan)
Advantage A CT scan can find cancer in the regional and non-regional lymph nodes, especially when the nodes become large in size because the test detects this size change. It is a good complementary test to investigate a suspicious region found on bone scan or plain X-ray.
The catch The test exposes the patient to radiation and until the lymph node becomes larger in size it cannot detect a possible cancer in that location.
Intravenous Pyelogram (IVP)
Advantage An IVP is used to provide an image of the kidneys, ureters, and bladder.
The catch The test exposes the patient to radiation. It is rarely used any more because newer devices are preferred.
Magnetic Resonance Imaging (MRI)
Advantage An MRI does not involve exposure to radiation. It may be able to find cancer in and around the prostate, such as the seminal vesicles or regional lymph nodes (stage N1). MRI can even find tumors in the spine, especially some high-grade tumors. The catch MRI is not good at detecting cancer in the lymph nodes unless a special iron oxide dye is used. It is not as useful as a bone scan for finding cancer in bony areas. Because the test utilizes a strong magnet, it cannot be used on individuals with metal in their bodies, such as from past medical procedures.
PET/CT Scan
Advantage This technology is rapidly developing. It may be able to pick up cancer in the organs, bone, or non-regional and regional lymph node metastasis very early when the nodes are still not large enough to be picked up by CT scan or MRI. It can sometimes detect cancer when a bone scan did not find cancer in the bones because it relies on a tracer compound to find even tiny tumors.
The catch The patient is exposed to radiation. Finding the right tracer marker (carbon-11, choline, glucose, NaF) to be used with the test is challenging because the technology is developing so quickly. In some cases, patients have problems with insurance coverage for this test.
ProstaScint Scan
Advantage The ProstaScint scan can suggest whether or not cancer has returned after localized treatment for prostate cancer, especially in the areas around the prostate.
The catch This test is of little value for a man with HRPC. Also, the accuracy of this test has been questioned.
Transrectal Ultrasonography (TRUS)
Advantage A TRUS involves no radiation exposure. It is the gold standard device to obtain prostate tissue biopsy samples.
The catch The TRUS is not a good test by itself for detecting a tumor in or near the prostate.
X-ray
Advantage In traditional X-ray procedures, the patient receives a low amount of radiation exposure. The tests can be done quickly.
The catch X-rays only show something when it is more obvious and takes up a lot of space, such as an infection, fracture, or cancer in the lungs or the ribs. They are not as good at finding small-to-moderate amounts of cancer or bone loss.
In upcoming chapters, we’ll consider a number of currently recognized FDA-approved treatments for HRPC and drugs that are in phase-3 testing. As you read those chapters, you will get more detailed information on the full scope of possible therapies to discuss with your physician to determine the best course of action for your individual situation. Following the sections on treatment, we’ll spend some time discussing side effects and offer suggestions on preventing and mitigating them. Remember, an informed patient can better weigh his options and make an educated choice on treatment plans.
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