Patient education: Treatment for advanced prostate cancer (Beyond the Basics)
- Nancy A Dawson, MD
Nancy A Dawson, MD
- Professor of Medicine
- Lombardi Comprehensive Cancer Center
- Georgetown University
- Section Editors
- Nicholas Vogelzang, MD
Nicholas Vogelzang, MD
- Section Editor — Prostate Cancer
- Professor of Medicine
- University of Nevada School of Medicine
- US Oncology Research
- W Robert Lee, MD, MS, MEd
W Robert Lee, MD, MS, MEd
- Section Editor — Prostate Cancer
- Professor of Radiation Oncology
- Duke University Medical Center
- Jerome P Richie, MD, FACS
Jerome P Richie, MD, FACS
- Section Editor — Cancer of the Urethra, Penis, and Ureter; Urologic Surgery; Prostate Cancer
- Elliott Carr Cutler Professor of Surgery
- Harvard Medical School
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 are 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 education: Prostate cancer treatment; stage I to III cancer (Beyond the Basics)".)
More detailed information about prostate cancer, written for health care providers, is available by subscription. (See 'Professional level information' below.)
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.
Men who have been treated for stage I or II ("localized") prostate cancer should be monitored with regular blood tests to check their prostate-specific antigen (PSA) level. If the PSA level rises, it suggests that the cancer has returned and possibly spread. Some men in this situation are treated similarly to men with stage IV (metastatic) prostate cancer. The decision of how to treat a man with a rising PSA is based on several different factors, including which treatments he has already had (and how the cancer responded), how quickly the PSA level is rising, and the likelihood that the cancer has started to spread to other parts of the body. (See "Patient education: 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. ADT is often combined with chemotherapy or abiraterone. (See 'Chemotherapy' below and 'Abiraterone' below.)
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 can also decrease the size of the cancer in the prostate as well as other areas (metastases). These treatments are called androgen deprivation therapy or ADT.
ADT can be done by taking medicines that interfere with androgens or by having surgery to remove the testicles (called an orchiectomy). In many countries, including 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" (meaning that they stop the production of androgens even though the testicles are not removed).
Examples of the medicines used in ADT include:
●GnRH agonists – Gonadotropin-releasing hormone (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 one to six months or as a depot that lasts 12 months, and they include leuprolide (sample brand name: Lupron) and goserelin (brand name: Zoladex).
●GnRH antagonist – Degarelix (brand name: Firmagon) is a GnRH antagonist that temporarily "turns off" the testicles' production of male hormones (androgens). This medicine is more rapidly acting than a GnRH agonist and may be useful for situations where there is major concern about the disease temporarily progressing before treatment becomes effective.
●Combined androgen blockade – 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. This boost can temporarily cause the cancer to flare (get worse). The antiandrogen blocks that flare.
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.
As mentioned, in many places, medication is preferred over surgery for ADT. However, in some countries, surgical castration is performed more frequently. There are also some situations in which surgery is done in order to decrease the testosterone level immediately, rather than waiting for medications to take effect. Some men may also choose to have surgery rather than take medication regularly for cost or convenience reasons. Men who do have surgery can get artificial (prosthetic) testicles implanted in order to preserve a normal appearance.
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 education: 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 education: 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 ADT, 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.
When to start treatment — Different doctors have different approaches for when to start treatment for advanced prostate cancer:
●Many doctors recommend starting treatment that includes 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 treatment 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.
Since everyone's situation is different, it's important to discuss the benefits and risks of each approach with your doctor in order to decide what treatments to have and when.
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. It is often given in combination with ADT as this can improve survival (how long a man will live).
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 a steroid to avoid a serious complication. Abiraterone's side effects can include fluid retention and a drop in potassium levels.
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.
Chemotherapy — Chemotherapy is a treatment given to slow or stop the growth of cancer cells. Chemotherapy is now often recommended in combination with ADT as the initial treatment for men whose cancer has already spread outside of the prostate, typically to bone or other organs. Chemotherapy given when treatment is first started may improve survival.
Chemotherapy is also commonly given to men with advanced prostate cancer who have stopped responding to their initial therapy, including all forms of hormone therapy.
The most commonly used chemotherapy agents are docetaxel (brand names: Docefrez, Taxotere) and cabazitaxel (brand name: Jevtana). Most of the drugs are given into the vein (intravenous [IV]).
The next steps in treatment depend on each individual's situation and his or her preferences, but they often include other hormonal therapies or more chemotherapy.
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 of blood cells that fight infection (white blood cells), which increases the risk of developing an infection
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 is often effective at relieving bone pain and preventing complications (broken bones, need for radiation therapy). In this setting, radium-223 has been shown to prolong life.
Secondary hormone therapy — Most men with advanced prostate cancer initially respond well to treatment that includes ADT, which is often given in combination with chemotherapy or abiraterone, but then their prostate cancer comes back, often within a few years. At this point, the cancer is termed "castration resistant" or "castrate resistant," meaning that ADT is no longer effective. Once this occurs, secondary hormone therapy is usually considered.
Even when prostate cancer becomes castration resistant, some form of ADT is 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 combined 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.
Immunotherapy — A newer approach to treating advanced prostate cancer involves immunotherapy. This is a type of treatment that uses the body's immune system to help slow or stop cancer growth.
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.
Side effects with this cancer vaccine have generally been mild and include chills, fever, fatigue, nausea, and headache.
Checkpoint inhibitor immunotherapy — Another immunotherapy approach is use of a group of medications called checkpoint inhibitors. "Checkpoints" are a built-in part of the immune system intended to prevent it from attacking healthy cells. Checkpoint inhibitors act on certain checkpoints in order to identify and destroy cancer cells. Several checkpoint inhibitors are used to treat other types of cancer; these work by stimulating cells called "T cells" in order to attack the cancer. These medications are not yet approved for use in people with prostate cancer, but they are being studied.
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 bone. Men whose metastases are mostly in their bones may also be treated with radium-233. (See 'Radium-223' above.)
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. 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 name: Xgeva) or zoledronic acid (brand name: 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:
Videos addressing common questions about clinical trials are available from the American Society of Clinical Oncology (http://www.cancer.net/pre-act).
WHERE TO GET MORE INFORMATION
Your health care 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 health care 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.
Patient education: Prostate cancer treatment; stage I to III cancer (Beyond the Basics)
Patient education: Gynecomastia (breast enlargement in men) (Beyond the Basics)
Patient education: Osteoporosis prevention and treatment (Beyond the Basics)
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.
Initial systemic therapy for castration-sensitive prostate cancer
Side effects of androgen deprivation therapy
Overview of the treatment of disseminated castration-sensitive prostate cancer
Bone metastases in advanced prostate cancer: Management
Castration-resistant prostate cancer: Treatments targeting the androgen pathway
Chemotherapy in castration-resistant prostate cancer
Immunotherapy for castration-resistant prostate cancer
Alternative endocrine therapies for castration-resistant prostate cancer
Bone metastases in advanced prostate cancer: Clinical manifestations and diagnosis
Prostate cancer: Risk stratification and choice of initial treatment
Rising serum PSA after treatment for localized prostate cancer: Systemic therapy
The following organizations also provide reliable health information.
●National Cancer Institute
●National Comprehensive Cancer Network
All topics are updated as new information becomes available. Our peer review process typically takes one to six weeks depending on the issue.