Advanced Prostate Cancer
Read Recent Breakthroughs in Advanced Prostate Cancer from UrologyHealth extra Winter 2014
Over 200,000 men are newly diagnosed with prostate cancer annually in the United States. With the likelihood of getting prostate cancer increasing with age, the advent of prostate cancer screening means cancer is being detected and treated earlier; however, approximately 5-10% of newly diagnosed prostate cancer cases involve advanced disease. In addition, some men may develop a recurrence of their cancer despite initial attempts at curative therapy such as surgery or radiation therapy. For more resources on prostate cancer visit our Know Your Stats ® site for the most up-to-date information.
Ideally, doctors prefer to find the disease in its earliest and most treatable stages. But for men diagnosed with advanced prostate cancer, the prognosis is getting better all the time. There are a number of effective treatments available. The information presented is a resource for physicians, patients, and caregivers on advanced prostate cancer and the current available treatment options.
However, before deciding on any treatment options it is important to understand that advanced prostate cancer is a very complex disease. While the following treatment options are available it does not mean they are the best option for you. It is critical that patients and physicians come together to map out a treatment solution that works well for a man’s over health and lifestyle. Prostate cancer and specifically advanced prostate cancer is a very individual disease and before deciding to take any treatment action is important to have a very open and honest discussion with your provider. If you need help finding a physician please use our Find a Urologist feature.
What is cancer?
Cells normally grow and divide in an orderly fashion, with old cells constantly being replaced with new cells. However, in cancer cells, this normally ordered process is interrupted and cells grow and are replaced in a completely unstructured way.
The extra cells form a mass called a growth or tumor. Tumors can be either benign (not cancerous) or malignant (cancerous). Benign tumors do not spread to other parts of the body, and are rarely a threat to life. Malignant tumors can spread (metastasize) and become life threatening.
What is primary cancer?
Cancer can begin in any organ or tissue and the original tumor site is called the primary cancer or primary tumor. It is usually named for the part of the body or the type of cell in which it begins.
What is metastasis, and how does it happen?
Metastasis means the spread of cancer. Cancer cells break away from the primary tumor and enter the bloodstream or lymphatic system (the system that produces, stores, and carries the cells that fight infections).
When cancer cells spread and form a new tumor in a different location, the new tumor is called a metastatic tumor. For example, if prostate cancer spreads to the bones, the metastatic tumor in the bone is made up of cancerous prostate cells (not bone cells). In this case, the disease in the bone is metastatic prostate cancer (not bone cancer).
What are the symptoms of metastatic cancer?
There are no distinct symptoms of metastatic cancer, often metastatic cancer is found through x-rays and additional tests performed for other medical reasons.
When symptoms of metastatic cancer occur, the type and frequency of the symptoms will depend on the size and location of the new growth. For example, a man whose prostate cancer has spread to the bones in his pelvis may have lower back or hip pain before he experiences any symptoms from the primary tumor in his prostate.
How does a doctor know whether a cancer is a primary or a metastatic tumor?
A pathologist examines a sample of the tumor under a microscope to determine whether the tumor is primary or metastatic. Cancer cells look like abnormal versions of cells in the tissue where the cancer began. Using specialized diagnostic tests, a pathologist is often able to tell where the cancer cells came from.
Metastatic cancers may be found before or at the same time as the primary tumor, or months or years later. When a new tumor is found in a patient who has been treated for cancer in the past, it is more often a metastasis than another primary tumor.
What are the types of advanced prostate cancer?
The commonly encountered disease categories of prostate cancer are summarized below. They range from prostate cancer that is confined to the prostate gland to prostate cancer that has spread outside of the prostate to the lymph nodes and bone. For more information on general prostate cancer please refer to our A to Z list
- Locally Advanced Prostate Cancer:
Cancer that has grown to fill the prostate or has grown through the prostate and may extend into the glands that help produce semen (seminal vesicles), or the bladder..
- Biochemically Recurrent Prostate Cancer (Rising PSA):
Patients who have a rising PSA after treatment, but do not show any evidence that the disease has spread to bone or other organs. This can occur after local treatment, or after hormone therapy. The management of such patients is controversial, and may include investigational treatments, radiation therapy, salvage surgery, hormone therapy, or chemotherapy.
- Metastatic Prostate Cancer (Hormone Sensitive):
Cancer that has spread (metastasized) to the bone, lymph nodes or other parts of the body. Through the depletion of the male sex hormone, testosterone or medications, improvement in the patient’s urinary function and pain control can be achieved.
- What is Castrate Resistant Prostate Cancer (CRPC):
Castrate Resistant Prostate Cancer (CRPC) is prostate cancer that continues to grow despite the suppression of male hormones that fuel the growth of prostate cancer cells.
What are Hormones and Androgens and their relationship to advanced prostate cancer?
Hormones are chemical messengers that are produced by the body’s glands and cause or control a particular bodily function. The human body produces and uses millions of hormones. In men, a critical class of hormones is called “androgens” and they have a wide range of functions.
Androgens are responsible for many uniquely male features including: lower voice, male hair patterns and the male libido, or sexual drive. In addition, androgens are extremely important in building muscle mass, increasing bone formation and stimulating red blood cell production. In essence, androgens affect every major tissue in the male body.
The two major androgens involved in prostate cancer are:
- dihydrotestosterone (DHT)
Testosterone, which is produced in the testicles, is often referred to as “the male sex hormone.” The male androgens have been shown to stimulate prostate cancer growth. DHT, the androgen that is created due to the metabolism of testosterone, is five times as potent a growth stimulator of prostate cancer when compared to testosterone.
What are the current treatments options for advanced prostate cancer?
It is important to know there is no cure for advanced prostate cancer. However, with advances in science men can control their cancer by slowing its growth and reducing the cancer related symptoms. Due to the lack of effective treatment options, intense efforts are under way to develop more specific, targeted therapies designed to improve the prognosis and quality of life of patients with advanced or recurrent prostate cancer, particularly those without cancer-related pain.
The most common types of therapy are described below:
- Hormonal Therapy/ Androgen Deprivation Therapy (ADT)
- LHRH (luteinizing-hormone releasing hormone) Antagonists /Gonadotropin releasing hormone (GnRH)
- LHRH (luteinizing-hormone releasing hormone) Agonists /Gonadotropin releasing hormone (GnRH)
- Anti-Androgen Therapy
- Combined Androgen Blockade (CAB)
- Estrogen Hormones
What is androgen deprivation therapy (ADT)?
Androgen deprivation therapy (ADT) refers to any treatment that lowers the body’s amount of androgen. Hormonal therapy or ADT for a prostate cancer patient is simply any method to deprive the man’s body of testosterone as a way to treat his prostate cancer. Because the hormone testosterone serves as the main fuel for prostate cancer cell growth, it’s a common target for therapeutic intervention in men with the disease. Studies suggest ADT started after prostate cancer has spread or metastasized to lymph nodes, the bones, or to other tissues provides a longer survival.
Traditionally, hormonal/ADT therapy has been used to treat men with prostate cancer that has spread beyond the confines of the prostate or for prostate cancer that is in an advanced/metastatic stage. Some doctors may prescribe ADT therapy even for earlier staged prostate cancer because it can shrink the local tumor and allow for more effective radiation treatment, especially for men with more aggressive localized disease. The use of this therapy is that it could potentially kill any cancer cell that could have escaped the prostate prior to, or during, other treatments and it may sensitize the tumor to radiation therapy.
Hormone therapy typically is effective for only a few years because as time progresses the cancer can grow in spite of the patients hormonal level being low. For this reason, hormone therapy is not a perfect strategy in the fight against prostate cancer, since it does not cure the disease. It also carries some unwanted toxicities. But it remains an important step in the process of managing advancing disease, and it will likely be a part of every man’s therapeutic regimen at some point during his fight against recurrent or advanced prostate cancer. Thus additional treatments are often needed to manage the cancer.
Who is a good candidate for ADT therapy?
Patients to be treated with ADT include men with regional spread of prostate cancer, men with early recurrence of prostate cancer (after prior treatments such as surgery or radiation), and men with metastatic prostate cancer.
What are the Side effects of using ADT for treatment?
The list of potential effects of testosterone loss is long:
- Diminished libido (sexual desire) occurs in 90 percent of men;
- Erectile dysfunction (inability to achieve or maintain an erection adequate for intercourse);
- Hot flashes similar to those experienced by women during menopause. They are characterized by a sudden spread of warmth to the face, neck and upper torso, usually followed by profuse sweating. Although uncomfortable, hot flashes pose no health risk and the effects may be controlled with medication;
- Weight gain of 10 to 15 pounds is a common;
- Mood swings;
- Depression which may be attributed to a variety of causes, including the treatment itself, reaction to side effects, or other cancer-related issues. Symptoms of depression include feelings of hopelessness, loss of interest in usually enjoyable activities, inability to concentrate and changes in appetite and sleeping patterns. Men experiencing depression are advised to speak to their physician or other member of their health care team about available resources;
- Fatigue is a feeling of extreme tiredness that may not be alleviated by rest or sleep. It is caused by decreased testosterone production;
- Anemia is a deficiency of red blood cells in the bloodstream, resulting in reduced oxygen to tissues and organs and feelings of tiredness or weakness. Anemia can be treated with medications, vitamins and minerals. Loss of muscle mass may manifest as decreased strength or weakness. A careful exercise program with progressive weight-bearing activities will improve strength.
- Osteoporosis, a long-term effect of hormone therapy is a loss of bone mineral density where the bones become thinner, more brittle and at increased risk for breaking. It is the same condition experienced by women in menopause. Osteoporosis can be treated with medications, calcium and vitamin D. An exercise program with progressive weight-bearing activities will also help strengthen bones. Since anemia is a common side effect of long-term androgen deprivation, blood tests are taken periodically after surgery.
- memory loss
- Cholesterol, especially the LDL cholesterol, tends to rise
- breast nipple tenderness
Long term ADT treatment often results in anemia, which is often mild but on occasion may be moderate to severe. Periodic monitoring of the routine blood count (CBC) while on ADT is advised. Other side effects of ADT include decreased muscle mass and strength, and bone loss that can result in osteoporosis. Studies have been published that indicate that bone loss is common in men with prostate cancer, even prior to starting ADT.
Since androgen deprivation will increase bone loss, attention should be given to approaches that focus on bone health (bone integrity). Low dose or intermittent hormonal therapy use may lessen these side effects. Weight gain is common in men on ADT. Therefore, caloric restriction, attention to carbohydrate intake and the need for a realistic exercise program are part of the supportive care for men on ADT.
Before beginning hormone therapy, every man should discuss the effects of testosterone loss with his doctor and alter his lifestyle in order to have better treatment outcomes.
What is Orchiectomy?
Orchiectomy is the surgical removal of the testicles, which produces the majority of the body’s testosterone. Although a surgical procedure, orchiectomy is considered hormone therapy because its purpose is to stop testosterone production.
Orchiectomy is a relatively simple surgery that is usually performed as an outpatient procedure. The operation may be performed under local or general anesthetic. A small incision is made in the scrotum, the sac that contains the testicles. The testicles are detached from blood vessels and the vas deferens (the tube that carries sperm to the prostate before ejaculation) and the sac is sewn back up.
What are the advantages of orchiectomy?
The procedure is relatively inexpensive, simple and has few risks. It needs to be performed only once and is effective almost immediately. Testosterone levels drop dramatically and the patient often has rapid relief from cancer symptoms.
What are the risks associated with orchiectomy?
The primary risks of orchiectomy are infection and bleeding. Death is a risk of all surgery involving general anesthesia, but is an extremely rare occurrence with this procedure. Many men are very uncomfortable with the idea of this kind of surgery since it is an irreversible operation. Concerns about body image or self-image may lead men to choose a non-surgical option.
What are the side effects of orchiectomy?
The removal of testosterone from the body may have many side effects some of which are similar to that seen in menopausal women. In addition, another major problem with orchiectomy is it can have a psychological impact upon a man. The look of the genital area and the effect of having the testicles removed may impact how a man feels about himself. However, this side effect can be managed with the use of a testicular prosthesis. Some men opt to have a testicular prosthesis, or artificial testicles, placed inside the scrotum to replace the testicles removed during surgery. The prosthesis makes the scrotum look much as it did before surgery. Also another option to maintain the look of the area is to have a subcapsular orchiectomy.
What is subcapsular orchiectomy?
An alternative to the standard orchiectomy procedure is that of subcapsular orchiectomy. In this technique the glands around the testicles that produce testosterone are removed but the testicles remain. Therefore the subcapsular orchiectomy procedure leaves the appearance of a near normal scrotum. This helps to prevent reported psychological effects associated with the removal of the testicles; another way around this is to insert saline implants.
What is luteinizing-hormone releasing hormone and how does it work to treat advanced prostate cancer?
This treatment options is often referred to as “medical orchiectomy” or “medical castration” because they are equivalent to the effect produced by orchiectomy (removal of the testicles). The important difference is that the medication can be stopped so the effects are reversible. These drugs act like a natural hormone by signaling the body to turn off testosterone production in the testicles.
The terms “luteinizing hormone” (LH) and “gonadatropin” (Gn) are variously used by different authorities. Thus, LHRH and GnRH are also interchangeable terms in the medical literature.
What are the two types of LHRH treatments?
LHRH (luteinizing-hormone releasing hormone) Antagonists/ Gonadotropin (GnRH): In this treatment, the drug interferes with brains signals, and blocks the luteinizing hormone-releasing hormone activity. In other words, LHRH is blocked from stimulating production ofluteinizing hormone (LH) and with no luteinizing hormone available, testosterone production is stopped. The most common LHRH antagonist treatment drugs are:
LHRH or GnRH antagonists generally do not produce the hormonal flare up seen often in the other ADT treatment. In other words, there is no short-term boost to testosterone production when a patient starts this therapy. This also reduces the need for short-term use of nonsteroidal anti-androgen therapy at the beginning of treatment. Some men have a severe allergic reaction to the LHRH antagonist drug therapy. Because of this risk, LHRH antagonists are used only for patients with advanced prostate cancer or who refuse any other type of hormone therapy due to preference or other side effects.
LHRH antagonists are injected through the buttocks at a doctor’s office. The injection will be made by either a doctor or a nurse on a weekly basis for an entire month. After the first month, the patient receives the antagonist only once a month. Patients are strongly encouraged not to miss appointments, and to schedule those appointments as close to exactly four weeks later as they can. After an injection, a patient will also wait at his doctor’s office for a period of time to ensure there is no allergic reaction.
LHRH antagonists are usually not recommended for patients who have irregular heartbeats, liver problems, or osteoporosis. Patients who are overweight are not recommended for this procedure. Patients with some of this conditions should speak with their doctors about whether LHRH antagonists are right for them. LHRH antagonists could exacerbate irregular heart beat and liver problems in addition to risking decreasing bone density. Researchers have found being over a particular weight could dramatically decrease the effectiveness of the drug.
After the first injection, patients should receive a blood test once every 8 weeks to ensure that his levels of testosterone have dropped to castrate level. Patients should also consider tests to monitor the functioning of the liver and their bone density.
LHRH (luteinizing-hormone releasing hormone) Agonists/Gonadotropin releasing hormone(GnRH):
LHRH agonists are synthetic analogs of the normal human hormone luteinizing hormone-releasing hormone, which is produced in the human hypothalamus. LHRH stimulates the production of a second hormone known as luteinizing hormone (LH which, under normal circumstances, stimulates testosterone production.
All LHRH agonists are small synthetic proteins and are structurally similar to normal human LHRH. However, they are much more powerful than the normal form. When a man with prostate cancer is first given an LHRH agonist, it has several effects:
- First, it stimulates production of LH, which then stimulates production of testosterone. This means that for a couple of weeks the patient’s testosterone level will usually rise instead of falling. This increase in the patient’s testosterone level can briefly stimulate increased growth of prostate and prostate cancer cells (with associated symptoms, such as increased bone pain, if the patient already has metastases to the bone). This has become known as the “flare response.” This response is short-lived in most patients, lasting for perhaps 7-10 days.
- Second, because the patient now has elevated levels of an LHRH agonist, the body stops producing any new normal LHRH. As a consequence, there is no further production of LH or testosterone. The level of hormone then drops by 90 to 95 percent, which is similar to castration levels. “Castrate level” is equivalent to the testosterone level of a man who has been surgically castrated by an orchiectomy.
- Third, because the testosterone level has dropped to castrate level, growth of prostate cells and prostate cancer cells is slowed to very low levels because there is very little testosterone to stimulate growth.
Thus injection of LHRH agonists can be used to manage the growth and spread of prostate cancer by largely shutting down certain normal hormonal functions in the male.
What are the advantages and disadvantages of using LHRH for treatment?
With this treatment men regularly see their physician not only to monitor for potential side-effects from the treatment but also to measure the levels of testosterone in the body. Some men like the idea of seeing their physician regularly because they feel like they are being active in the treatment of the disease. However, other men find the very same visits a disadvantage because of time and schedule requirements.
Another advantage of LHRH therapy is the elimination of the need for an orchiectomy in those men preferring not to have the surgery. Furthermore, an advantage to LHRH therapy is that the side effects associated with the disease are potentially reversible depending on the length of time that a man has been on treatment.
The main disadvantage to LHRH is the costs associated with the treatment. The injections are cumulatively more expensive than a one-time surgical procedure. This cost factor becomes a major financial burden if a man’s health insurance does not cover the treatment.
What is Anti-Androgen Therapy?
An additional medical therapy to inhibit testosterone involves blocking the site of interaction of testosterone with cells normally stimulated by testosterone.
Anti - androgens work by blocking the testosterone receptors in the prostate cells. Normally, testosterone would bind with these receptors and fuel the growth of prostate cancer cells. With the receptors blocked, testosterone cannot “feed” the prostate. Anti - androgen therapy does not eliminate testosterone and therefore may have fewer or less severe side effects than those associated with surgical and medical castration.
The three most common anti - androgen drugs are
These drugs are taken orally as either a tablet or a pill. A single dose usually contains between 50 mg and 150 mg, depending on the patient’s needs and doctor’s prescription. Doctors encourage their patients to take the drug around the same time everyday to ensure a steady stream of therapy. Patients who forget to take a dose and are close to a time where they usually take the next dose, should not take a double dose. Taking a dose around the same time each day will decrease the incidence of some side effects, such as nausea or vomiting.
What are the advantages and disadvantages of Anti-Androgen therapy?
The main advantage of anti-androgens is that they do indeed block testosterone from binding to its receptor, as well as any residual testosterone that may not be blocked by LHRH therapy.
The main disadvantages include cost and compliance as well as drug-related side effects. Some of these medicines must be taken several times per day and men may forget to take all the needed medicine. It is important to take all the prescribed doses of these medicines so that they have their maximal benefit. Like the LHRH agents, these medicines are expensive and may be a burden for those men whose insurance does not cover oral anti-cancer medicines.
What are the side effects of Anti-Androgen therapy?
All three FDA-approved anti-androgens may cause liver dysfunction. Typically, your doctor will monitor your liver with blood tests periodically and will discontinue the anti-androgen if liver abnormalities occur.
The anti-androgen flutamide may cause diarrhea and nilutamide may cause a delayed adaptation to darkness, which may affect nighttime driving. In rare cases the drug has been known to cause lung fibrosis.
What is Combined Androgen Blockade (CAB)?
The use of castration in addition to anti - androgens is called combined androgen blockade (CAB). The use of anti - androgens a few weeks before LHRH agonists are started has been shown to significantly reduce the incidence of hormone flare that can be painful dangerous for patients with distant bone metastasis. Anti – androgens can also be used after surgical or medical castration stops being effective. There are a few studies that indicate using anti - androgens as monotherapy may be slightly less effective than medical or surgical castration as monotherapy. Other studies found no difference in the survival rates of people who had used only one form of treatment.
What is chemotherapy?
Chemotherapy is a treatment in which drugs circulate throughout the body and bloodstream and can kill any rapidly growing cells, including both cancerous and non-cancerous ones. Often, chemotherapy is not the primary therapy for prostate cancer patients, but it is for men with advanced stages of prostate cancer, or whose cancer has metastasized, or spread from the prostate gland to other parts of the body and has become resistant to hormone therapy.
Currently, the standard of care for men with metastatic prostate cancer that has spread and is progressing despite low levels of testosterone is treatment with a form of chemotherapy drug regimen. The decision on when to start chemotherapy is difficult and highly individualized based on several factors:
- What other treatment options or clinical trials are available.
- How well chemotherapy is likely to be tolerated.
- What prior therapies you have received.
- If radiation is needed prior to chemotherapy to relieve pain quickly.
Often chemotherapy is given before pain starts, with the goal of preventing the pain from cancer spreading to bones and other sites.
What are the side effects of chemotherapy treatment?
The most common side effects of chemotherapy are:
- nausea and vomiting,
- hair loss,
- taste changes,
- decrease in blood cell counts that result in an increased risk of infections.
To minimize the side effects, chemotherapy drugs are carefully monitored according to the amount and number of times they are administered. Supportive medication is also given to offset the side effects caused by the drugs. Most side effects disappear once chemotherapy is stopped.
Are there new chemotherapy treatment options that I may benefit from?
In 2004, data was presented from two scientific studies demonstrating for the first time that chemotherapy treatment could extend the survival of patients with advanced prostate cancer.
Data demonstrated that treatment regimens including docetaxel chemotherapy extended median survival more than two months in patients with CRPC no longer responsive to hormone therapy.
Based upon the data and other scientific studies, the FDA has approved docetaxel for use in combination with prednisone as the first registered treatment for patients with castrate resistant, metastatic prostate cancer. When taken with the steroid prednisone, the combination therapy has proven to extend survival by several months. In addition two new chemotherapy drugs have been approved for the treatment of CRPC they are called cabazitaxel and abiraterone acetate. Cabazitazel is the first drug to show a survival benefit in patients whose disease has progressed after standard chemotherapy and for whom there are currently no approved treatment options.
What is Immunotherapy?
Immunotherapy exploits the immune system to delay or halt malignant growth either by targeting tumor-associated antigens (TAAs) or by disrupting molecular pathways that promote tumor growth. The underlying mechanism making vaccines so successful is the stimulation of protective immune responses directed against target antigens that are expressed by the infectious agent but not by the host’s own cells. The application of therapeutic cancer vaccines differs fundamentally from these preventative approaches because they are applied in patients with existing disease, predominantly advanced or metastatic carcinomas.
In addition, a new immunotherapy for the treatment of advanced prostate cancer, called Provenge has been approved by the FDA and does appear to extend the survival by several months for patients.
Provenge is an immune therapy created by harvesting immune cells from a patient, genetically engineering them to fight prostate cancer, and then infusing them back into the patient. It is approved only for treatment of patients with few or no symptoms and have prostate cancer that has spread outside the prostate and have become resistant to hormone therapy.
Can female hormones be used to treat advanced prostate cancer?
Yes, as a final option, estrogen therapy can be added to the mix because estrogen also decreases male hormone levels. Although the drug has proved to be effective in counteracting the effects of testosterone and in slowing the growth of prostate cancer, continuous estrogen therapy has been associated with increased cardiovascular side effects including blood clots and strokes, and is therefore often administered along with an anticoagulant drug.
Because estrogen is one of the main hormones that affect female characteristics, other side effects of its use include, increased breast size and tenderness. As a result, estrogen treatment is usually not given unless other ways of reducing testosterone levels are no longer effective.
Frequently Asked Questions
What is Intermittent Therapy?
Over the years, researchers have explored different ways to minimize the side effects of testosterone loss while maximizing the therapeutic effect of hormone therapy. The most commonly explored strategy is known as intermittent therapy.
This strategy takes advantage of the fact that once LHRH agonists are removed it takes a while for testosterone to begin circulating in the body again.
With intermittent hormone therapy, the LHRH agonist is used for six to twelve months, during which time a low PSA level is maintained. The drug is stopped until the PSA rises to a predetermined level, at which point the drug is restarted. The "drug holidays" in between cycles allow men to return to nearly normal levels of testosterone, potentially enabling sexual function and other important quality of life measures to return before the next cycle begins again.
At this time, however, the true benefits of this approach remain unclear, and large clinical trials are currently underway to evaluate its use in men with advanced prostate cancer. If the approach proves to be as effective as continuous therapy in suppressing tumor growth, intermittent therapy will likely become popular because of potential for an improved side effect profile.
What is Castrate Resistant Prostate Cancer (CRPC)?
If a patient has a rising PSA while on androgen deprivation therapy, that is referred to as castrate resistant prostate cancer. When first treated, advanced prostate cancer usually responds to hormone treatments and the disease progression is stabilized. However, stabilization of the disease depends heavily on where the patient is in the disease process. Sometimes cancer cells can outsmart the treatments and learn how to thrive, even without male hormones. Doctors call this condition castrate resistant prostate cancer. They treat this type of prostate cancer with chemotherapy
How accurate is the PSA test when it comes to remission? Can I trust that low PSA values means I am disease-free?
Having a low PSA value does not mean that you are disease free but it also does not mean you have recurrent prostate cancer. Generally, if a patient has recovered gonadal function (normal testosterone) then an undetectable (after surgery) or low and stable (after radiation) is consistent with no evidence of progression. However, if a patient has a rising PSA, it depends on the clinical situation, the nuances of how significant the cancer was prior to treatment, and the specific treatment and the pattern of PSA recurrence.
PSA is produced by all prostate cells, not just prostate cancer cells. At this point your cancer cells have either been removed or effectively killed. Some cells might have spread outside the treatment areas before they could be removed or killed and it is these cells that can begin to multiply and produce enough PSA that can become detectable by lab tests.
Therefore, PSA is not really a marker for disease progression, but a marker for prostate cell activity. Doctors don’t usually look at only one PSA reading, they review and watch and see how the numbers progress. In general, after surgical removal of the prostate, most physicians believe the PSA level should be undetectable. There are a couple of ways that the PSA is used to determine recurrence of disease:
- Defined by a rise above PSA 0.2 ng/ml.
- Defined by three consecutive PSA rises above the lowest PSA level. For example, consider a man’s PSA is 0.2 ng/ml after treatment and then rises to 0.7 ng/ml, then 1.8 ng/ml, is held at 1.8 ng/ml, then goes to 2.9 ng/ml and finally reaches 4.4 ng/ml. Since there were not three consecutive PSA rises, this patient would still be considered free of prostate cancer, even though his PSA went from 0.2 to 4.4 ng/ml. If his PSA were to go to 7.3 ng/ml, he would experience three consecutive rises and would be considered as having recurrent prostate cancer.
- Defined by a rise of 2.0 ng/ml above the lowest level achieved. If a man’s PSA fell to 0.2 ng/ml, then to 0.7 ng/ml, followed by 1.1 ng/ml, then 1.4 ng/ml, then 1.6 ng/ml, and finally 1.9 ng/ml, this man would still be classified as prostate cancer free even though his PSA is rising. To be classified as having recurrent cancer, the PSA would have to have risen to 2.2 ng/ml.
The reason that doctors look for confirmation from multiple tests following radiation is that the PSA can "bounce" or jump up for a short period after radiation therapy, and will then come back down to its normal level. If they relied only on the one elevated PSA, it’s possible that they could have tested during a bounce phase, and the results will therefore be misleading. This PSA bounce typically occurs between 12 months and 2 years following the end of initial therapy.
If your PSA is rising but doesn’t quite reach these definitions, your doctor might be tempted to start initiating further therapy anyway. Remember that PSA is only one of many factors that help to determine your prognosis after treatment. The original clinical stage of disease, your pre-diagnostic PSA, and your overall health and life expectancy are also key factors in assessing the aggressiveness of your disease, so be prepared to discuss treatment options even if you don’t fit the classical categories for PSA rise after initial therapy.
On the other hand, if your PSA is rising and you do fit the categories defined above, that doesn’t necessarily mean that your situation is dire. What researchers have been finding over the past few years is that universal PSA cut-offs might not be sufficient for truly understanding how prostate cancer grows.
Where can I go for more information?
Hormone Health Network's Osteoporosis and Men's Health Fact Sheet.
Hormone Health Network's Prostate Cancer and Bone Loss Fact Sheet.
Reviewed: January 2011
Last updated: May 2014
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