Prostate cancer is a cancer of the prostate gland, an organ that forms a ring around the urethra, near its connection to the bladder (figure 1). The urethra is the tube that carries urine from the bladder to the outside of the body.
Prostate cancer is advanced if it has spread beyond the prostate gland and the area around the prostate. Some men with newly diagnosed prostate cancer have advanced, or stage IV, prostate cancer. In other men, advanced prostate cancer will develop after they were originally treated for localized disease.
Advanced prostate cancer is usually treated with a combination of treatments, which may include hormone therapy, chemotherapy, immunotherapy, or radiation. Although advanced prostate cancer is not curable, treatment can often help to control the cancer for prolonged periods of time. This can help to reduce symptoms and improve the quality of life.
This article will discuss the treatment of men with advanced prostate cancer. A separate article discusses the treatment of stage I to III prostate cancer. (See "Patient information: Prostate cancer treatment; stage I to III cancer (Beyond the Basics)".)
More detailed information about prostate cancer is available by subscription. (See "Overview of the treatment of disseminated prostate cancer".)
PROSTATE CANCER STAGING
Staging is a system used to describe the size, aggressiveness, and spread of a cancer. A cancer's stage helps to guide treatment and can help predict the chance of curing the cancer.
Stage IV prostate cancer (also called metastatic prostate cancer) has spread outside the prostate (beyond the seminal vesicles, to areas like the bladder or rectum) (figure 1). Stage IV cancer can also spread to the lymph nodes or other more distant areas, like the bones.
Some men with a rising serum prostate specific antigen (PSA) are treated similarly to men with stage IV prostate cancer. (See "Patient information: Prostate cancer treatment; stage I to III cancer (Beyond the Basics)", section on 'Treatment of rising PSA'.)
STAGE IV (METASTATIC) PROSTATE CANCER TREATMENT
Androgen deprivation therapy (ADT) is usually recommended as the initial treatment for men with metastatic prostate cancer. In cases where disease is advanced (high volume) at the time of initial treatment, ADT is often combined with chemotherapy.
Androgen deprivation therapy — Male hormones (androgens, the most common of which is testosterone) fuel the growth of prostate cancer. Treatments that decrease the body's levels of androgens (called androgen deprivation therapy, or ADT) decrease the size of prostate cancer.
ADT can be done by taking medicines that interfere with androgens or by having surgery to remove the testicles (called an orchiectomy). In the United States, the use of medicines is usually preferred over surgery. The medicines used in this context have the same effect as surgery, as they are a form of “chemical castration”. (See "Initial therapy for castration sensitive metastatic prostate cancer".)
Examples of the medicines used in ADT include:
●GnRH agonists — GnRH agonists are medicines that temporarily "turn off" the testicles' production of male hormones (androgens). This starves the cancer cells, causing the prostate to shrink. GnRH agonists are given as a shot every three to twelve months and include leuprolide (sample brand name: Lupron) and goserelin (brand name: Zoladex).
●Combined androgen blockade (CAB) — Some doctors recommend a second medicine, called an antiandrogen, in addition to the GnRH agonist. Examples of antiandrogens include flutamide (sample brand name: Eulexin) and bicalutamide (brand name: Casodex). These medicines are especially helpful when GnRH agonists are being started. That’s because GnRH agonists actually boost androgen production for a short time at the beginning – before they shut down its production.
Men taking a GnRH agonist generally take this medicine continuously. Although some doctors have suggested taking breaks by being off treatment (“intermittent ADT”), this approach has not been shown to be fully equivalent.
Side effects of ADT — The side effects of ADT are related to the lowered levels of male hormones and include:
●Decreased libido (sex drive) and difficulties with erection (erectile dysfunction)
●Enlargement of the breasts (called gynecomastia) (see "Patient information: Gynecomastia (breast enlargement in men) (Beyond the Basics)")
●Loss of muscle and an increase in body fat
●Thinning and weakening of the bones (called osteoporosis), which can increase the risk of bone fractures (see "Patient information: Osteoporosis prevention and treatment (Beyond the Basics)")
●An increased risk of developing type 2 diabetes
●An increased risk of developing or worsening coronary heart disease, which can lead to heart attack
Many of these side effects are serious, and they might seem frightening. Not all men have these side effects. In addition, it is important to balance the risk of side effects with the risk of not using androgen deprivation, which could allow your cancer to grow or spread. In most men, the risk of the cancer growing or spreading outweighs the possible risk of side effects. In addition, there are ways to prevent or treat many of these side effects. (See "Side effects of androgen deprivation therapy".)
When to start ADT — Experts disagree about the best time to start ADT.
●Many doctors recommend starting ADT when metastatic prostate cancer is first diagnosed; the hope is that treatment will slow the growth of the cancer and possibly prolong survival.
●Others believe that early ADT is not curative and can cause bothersome side effects. Doctors in this group recommend delaying the start of treatment until symptoms of cancer (like bone pain) develop.
Discuss the benefits and risks of each approach with your doctor.
Secondary hormone therapy — Most men with advanced prostate cancer initially respond well to ADT, but then prostate cancer comes back within two years. At this point, the cancer is termed “castration-resistant” or “castrate resistant”, meaning that ADT alone is no longer effective. Once this occurs, secondary hormone therapy is usually considered. (See "Secondary endocrine therapies for castration resistant prostate cancer".)
Even when prostate cancer becomes castration-resistant, some form of ADT is usually continued because at least a portion of the cancer cells might still respond.
Secondary hormone therapy can include:
●Adding an antiandrogen (such as bicalutamide, nilutamide, or flutamide) in men who have thus far been treated only with GnRH agonists.
●Stopping the antiandrogen in men who were treated with complete androgen blockade.
●Trying a different type of antiandrogen. Cancer that is resistant to one antiandrogen treatment may not be resistant to another.
●Trying another medicine that blocks the activity of androgen in the body, including estrogen, steroids, or the antifungal medication ketoconazole.
Abiraterone — Abiraterone (brand name: Zytiga) is a medication drug that blocks the production of androgens by the prostate cancer itself, as well as in the testes and adrenal glands. Abiraterone has been shown to improve survival in men with advanced prostate cancer – whether or not they have already been treated with chemotherapy. Abiraterone must be taken with prednisone to avoid a serious complication. Abiraterone’s side effects can include fluid retention and a drop in potassium levels. (See "Castration resistant prostate cancer: Treatments targeting the androgen pathway", section on 'Abiraterone'.)
Enzalutamide — Enzalutamide (brand name: Xtandi) is another new agent that blocks the effects of androgens in stimulating the growth of the prostate cancer cells. Enzalutamide has been shown to increase survival in men who have been treated with chemotherapy. It has also been shown to increase survival in men who have not yet received chemotherapy, and to delay both the progression of the disease and the need for chemotherapy in men who have not yet had chemotherapy.
Radium-223 — Radium-223 is a radioactive element that localizes in bone. For men whose advanced prostate cancer consists almost exclusively of extensive bone metastases, treatment with radium-223 may be effective at relieving bone pain, preventing complications (broken bones, need for radiation therapy), and prolonging life.
Immunotherapy — A newer approach to treating advanced prostate cancer involves harnessing or strengthening the body’s own immune response to attack the cancer.
Cancer vaccine — One form of immunotherapy involves the use of a cancer vaccine called sipuleucel-T (brand name: Provenge). This vaccine is made by isolating white blood cells (dendritic cells) from the patient’s blood and stimulating them outside the body with various chemicals to build the body’s immunity against the cancer. These cells are then reinjected into the patient three times, at intervals of two weeks. (See "Immunotherapy for castration-resistant prostate cancer", section on 'Sipuleucel-T'.)
Side effects with this cancer vaccine have generally been mild and include chills, fever, fatigue, nausea, and headache.
Monoclonal antibodies — Another form of immunotherapy that involves the use of so-called monoclonal antibodies is under investigation. One such antibody, called ipilimumab (brand name: Yervoy), works by stimulating the actions of immune cells that attack the cancer called T cells. It has shown promise and is already being used to treat advanced melanoma, but has not yet been approved to treat prostate cancer.
Chemotherapy — Eventually, most men with advanced prostate cancer stop responding to all forms of hormone treatment. The next step in treatment depends on each individual’s situation and his preferences, but often includes chemotherapy. (See "Chemotherapy in castrate-resistant prostate cancer".)
Chemotherapy is a treatment given to slow or stop the growth of cancer cells. Most treatments involve a combination of several chemotherapy drugs (called regimens), which in the case of prostate cancer usually includes an agent called docetaxel (brand names: Docefrez, Taxotere) or one called cabazitaxel (brand name: Jevtana). Most of the drugs are given into the vein (intravenous, IV).
Chemotherapy is not given every day but instead is given in cycles. A cycle of chemotherapy (which is typically 21 or 28 days) refers to the time it takes to give the treatment and then allow the body to recover from the side effects of the medicines.
Side effects of chemotherapy can include:
●Temporary hair loss
●Nausea and vomiting
●A decrease in the number blood cells that fight infection (white blood cells), which increases the risk of developing an infection
BONE PAIN TREATMENT
The bones are a common place for prostate cancer to spread. Androgen deprivation therapy can often control the cancer that has spread to bones.
Men who develop bone pain in one or a few bones as a result of the cancer can be treated with radiation therapy to relieve their pain. The radiation is usually given in one or a few visits, similar to having an X-ray. (See "Bone metastases in advanced prostate cancer: Clinical manifestations and diagnosis".)
Some people have worsened pain for one to two days immediately after the radiation treatment. However, most people feel partial or complete improvement of pain within a week after treatment.
Men with bone metastases can also benefit from medicines called osteoclast inhibitors, such as denosumab (brand names: Prolia, Xgeva) or zoledronic acid (brand names: Reclast, Zometa). These medicines can help prevent fractures, the need for bone surgery, spinal cord compression, and the need for radiation therapy to treat pain.
Progress in treating cancer requires that better treatments be identified through clinical trials, which are conducted all over the world. A clinical trial is a carefully controlled way to study the effectiveness of new treatments or new combinations of known therapies. Ask for more information about clinical trials or read about clinical trials at:
WHERE TO GET MORE INFORMATION
Your healthcare provider is the best source of information for questions and concerns related to your medical problem.
This article will be updated as needed on our web site (www.uptodate.com/patients). Related topics for patients, as well as selected articles written for healthcare professionals, are also available. Some of the most relevant are listed below.
Patient level information — UpToDate offers two types of patient education materials.
The Basics — The Basics patient education pieces answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials.
Beyond the Basics — Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are best for patients who want in-depth information and are comfortable with some medical jargon.
Professional level information — Professional level articles are designed to keep doctors and other health professionals up-to-date on the latest medical findings. These articles are thorough, long, and complex, and they contain multiple references to the research on which they are based. Professional level articles are best for people who are comfortable with a lot of medical terminology and who want to read the same materials their doctors are reading.
The following organizations also provide reliable health information.
●National Cancer Institute
●National Comprehensive Cancer Network
●National Library of Medicine