Men living with metastatic prostate cancer now have more options available than ever before.
Each year, nearly 240,000 American men are diagnosed with cancer of the prostate gland. It is the most common cancer affecting men, other than skin cancer, and occurs mainly in men aged 65 or older.
Most of the time when prostate cancer is diagnosed and treated, the tumor is still confined to the gland. But prostate cancer can spread to other parts of the body. If that happens, there are treatments available that can stop cancer growth, control pain and other symptoms and extend survival.
If a man has already been treated for prostate cancer with surgery or radiation, rising levels of PSA may mean that his prostate cancer has returned. (PSA refers to “prostate-specific antigen,” a protein produced by the prostate gland.) If the level of PSA rises and tests cannot detect any tumor cells in the bone or other organs, the cancer is considered “micrometastatic.” That is, doctors believe cancer cells are somewhere in the body, even though they cannot be found.
The standard of care for treating metastatic prostate cancer (cancer that has spread from the prostate to other parts of the body) is hormonal therapy. This type of treatment is aimed at stopping the production of testosterone and other male hormones. Testosterone acts like a fuel, encouraging prostate cancer to grow. Without testosterone and other male hormones, prostate cancer goes into remission, often for many years. (Remission is when all signs and symptoms of cancer disappear.)
Testosterone production is usually reduced by:
Injecting medications called LHRH analogs (or antagonists) that block signals from the brain to the testes. Because the testes no longer receive “instructions” from the brain to make testosterone, they shut down production of the hormone. The medications used include triptorelin (Trelstar), leuprolide (Eligard, Lupron, Viadur and others), goserelin (Zoladex) and degarelix (Firmagon). The drugs often are given over several months.
Combining LHRH analogs with antiandrogens. When the signals between the brain and the testes have been blocked by LHRH drugs, men with metastatic prostate cancer may experience a surge of testosterone. This can stimulate the growth of the cancer or cause symptoms. So doctors add antiandrogens to LHRH medications. The antiandrogens prevent testosterone in the bloodstream from attaching to tumor cells and making them grow. Examples of antiandrogens include flutamide (Eulexin and others), bicalutamide (Casodex and others) and nilutamide (Nilandron). These medications are taken daily as pills.
Because one of the liver’s important jobs is to break down medications as well as toxins in the body, the liver’s function needs to be checked with periodic blood tests, especially if you are taking antiandrogens. Tell your doctor immediately if you experience nausea, vomiting, stomach pain, extreme tiredness, loss of appetite, flu-like symptoms, dark yellow or brown urine and/or yellowing of the skin or eyes. It’s crucial to remember that herbal remedies, megadoses of vitamins or excessive amounts of alcohol can prevent the liver from breaking down antiandrogens and can cause abnormal test results.
When first treated with hormonal therapy, metastatic prostate cancer usually responds to the treatments and goes into remission. But sometimes cancer cells can resist treatments. Prostate cancer cells can “learn” how to grow, even without male hormones. Doctors call this condition hormone-resistant prostate cancer.
In some cases of hormone-resistant prostate cancer, simply stopping antiandrogen treatment causes a man’s PSA level to go down and his prostate cancer to shrink or disappear. In other cases, doctors prescribe different antiandrogen drugs to try to slow cancer growth.
Chemotherapy and Other Drugs
Sometimes doctors recommend chemotherapy as a treatment for hormone-resistant prostate cancer. Doctors usually give chemotherapy to men who fall into one of three groups:
• Those with fast-rising PSA levels. When the PSA level begins doubling or tripling so quickly that hormone treatments can’t control it, chemotherapy may be an option.
• Those who are developing symptoms. If a man with metastatic prostate cancer is losing weight, looking pale and experiencing physical distress, chemotherapy should be considered.
• Those who have metastatic disease that is growing quickly. Sometimes, these men are treated with radiation aimed at multiple tumor sites. However, many radiation treatments to the bone can reduce the number of red blood cells in the bone marrow and lead to anemia. (In anemia, a lowered level of red blood cells may result in fatigue and other symptoms such as dizziness or headache.) Using chemotherapy reduces the need for radiation.
The standard chemotherapy used for men with hormone-resistant prostate cancer that has spread is docetaxel (Taxotere and others). It is used in combination with the steroid prednisone.
If docetaxel stops working or does not work, patients may be given cabazitaxel (Jevtana), a newer chemotherapy approved by the U.S. Food and Drug Administration (FDA) for prostate cancer that resists treatment.
A number of other types of drugs have been approved by the FDA for advanced prostate cancer that no longer responds to hormone treatments or chemotherapy. These drugs include:
Sipuleucel-T (Provenge). This medication works by using the body’s own specialized white blood cells, which are important parts of the body’s immune system, to destroy prostate cancer cells. Sipuleucel-T is given as a series of three infusions into a vein, with about two weeks between each infusion. A few days before each treatment, some of the patient’s white blood cells are removed from the blood. The white blood cells are exposed to a protein that trains them to target and destroy prostate tumor cells. These newly trained white blood cells become a personalized dose of sipuleucel-T, which is then returned to the man’s bloodstream.
Abiraterone (Zytiga). Used with prednisone, this hormone therapy can be given before or after chemotherapy. Abiraterone is a tablet, usually taken once a day. It blocks the production of male hormones made in the testes, within prostate tumors and within the adrenal glands. (The adrenal glands sit on top of the kidneys and make various hormones that help control heart rate and blood pressure, among other body functions.)
Enzalutamide (Xtandi). This drug blocks male hormones from attaching to prostate cancer cells and helping them grow. As a result, enzalutamide slows the growth of prostate tumors and destroys them. Right now, this drug is approved for use only in men who have previously received docetaxel.
Radium Ra 223 (Xofigo). Radium Ra 223 is a drug that contains a small amount of radiation and is injected into the bloodstream. The radiation seeks out prostate cancer cells that have spread to the bone and that may cause pain. Radium Ra 223 was approved by the FDA for men whose cancer has spread only to the bones and has not responded to other treatments.
Managing Side Effects
It’s important to talk with your doctor about the possible side effects of prostate cancer and its treatment. Members of your health care team can help you reduce and manage these symptoms to improve your quality of life.
Hot flushes. In most men treated with hormonal therapy for metastatic prostate cancer, hot flushes are fairly limited. If you are especially troubled by hot flushes, ask your doctor about medications that can help, such as low doses of female hormones (estrogen or progesterone) or antidepressants such as venlafaxine (Effexor and others) or sertraline (Zoloft and others).
Osteoporosis (increased risk of bone fractures). Lowered testosterone levels lead to a loss of calcium, which may cause osteoporosis (thinning, brittle bones). Treatment with bisphosphonates, such as zoledronic acid (Zometa), or denosumab (Xgeva) can help reverse the effects of osteoporosis. This is especially important to reduce bone pain as well as the risk of fractures to bones, including the hip and spine.
Bone pain. Prostate cancer that spreads to the bone can lead to pain. Medications such as bisphosphonates help relieve some of this pain. In addition, radiation is often used to manage bone pain. Men with metastatic prostate cancer typically receive 10 radiation treatments over about two weeks. It usually takes a week before the pain and discomfort begin to ease.
Loss of erections (erectile dysfunction). Sometimes men experience erectile dysfunction when being treated for prostate cancer. If you are experiencing this side effect, discuss your concerns with your doctor. He or she can recommend a number of possible treatments. Some approaches used to manage this side effect include:
• A drug such as sildenafil (Revatio, Viagra and others), vardenafil (Levitra, Staxyn and others) or tadalafil (Adcirca, Cialis) can improve erections for some men;
• A penile implant that makes it possible to have and keep an erection. This approach involves surgery;
• Urethral suppositories or injections of prostaglandin E1 (alprostadil [Caverject and others]) to promote erections;
• Vacuum devices that draw blood into the penis for an erection.
Loss of bladder control (incontinence). After radiation treatment, incontinence can occur, but not right away. It could begin as long as 18 months later. After a prostatectomy (surgical removal of the prostate), incontinence often occurs right away, although usually it is temporary and improves with time. Talk with your doctor about what you can expect after treatment and the best way to cope with this side effect. Some ways to manage incontinence include:
• Medications such as solifenacin (VESIcare) or tolterodine (Detrol and others) that can calm the bladder and relieve symptoms;
• Special exercises called Kegel exercises (squeezing specific muscles in the pelvis);
• Drugs such as duloxetine (Cymbalta) that improve the function of the sphincter muscle, which controls the flow of urine;
• Surgical procedures in some cases can benefit men with incontinence. An artificial urinary sphincter has been used successfully since 1980.
Weight gain. When men’s testosterone levels go down, their metabolism can change, causing them to retain fluid and gain weight. Hormone treatments can result in a loss of muscle mass. Stay active by walking, doing chores and engaging in physical activities you enjoy. Weight training can also help build and maintain muscle strength and structure.
Fatigue. Some days you may feel so tired that even simple daily activities leave you exhausted. But over time, light physical activity or gentle exercise—short walks building up to longer walks—go a long way toward helping relieve fatigue. Taking 30-minute “power naps” during the day also can help. These naps give you a boost without disrupting your sleep schedule.
Frequently Asked Questions
Q. I find hormonal therapy very difficult, emotionally. I’ve read that this reaction might be related to a lack of estrogen. If that’s the case, why aren’t estrogen patches used more widely?
A. There is some suggestion that lowered estrogen levels could have something to do with your difficulties. But using a patch could create its own problems. For instance, estrogen can lead to fluid retention, congestive heart failure and an increased risk of blood clots. A lower dose of estrogen would be safer but also less effective. This is why estrogen patches and supplements aren’t used as much as they have been in the past. You might consider individual counseling, which helps many people cope with the emotional challenges raised by cancer and its treatment.
Q. When prostate cancer metastasizes, does the PSA level go up?
A. In general, higher-than-normal PSA levels signal that something has changed in the prostate gland. If a man has been treated for prostate cancer with surgical removal of the gland, most physicians believe that PSA levels should be very low—that is, less than 0.2 nanograms per milliliter (ng/mL) of blood. If the PSA number goes up during two consecutive readings after surgery, it may mean that prostate cancer has returned or spread from its original site to other organs. In men who have been treated with radiation, doctors look for three consecutive rises in the PSA number. They may also order other tests to further evaluate the situation.
Q. Can I continue to do exercise, like brisk walking, when I am treated for metastatic prostate cancer?
A. It’s certainly a good idea to engage in as much physical activity as is comfortable. Exercise helps promote heart health and can relieve stress and fatigue. In general, activities like walking or swimming are preferable to high-impact activities, such as jogging. Men who are having a difficult time finding an exercise routine that works for them should seek the help of a physical therapist or rehabilitation specialist.
Q. Is it appropriate to have radiation treatment for metastatic prostate cancer even though I was already treated with radiation before the cancer spread?
A. In general, if you have already received radiation to the pelvis near the prostate gland, more radiation to that area would not be recommended. But if you develop a problem such as pain in the bones of the arms, legs or spine and those areas have not been exposed to radiation before, you most likely could be treated with radiation to those areas.