Treatment for advanced prostate cancer

Treatment for advanced prostate cancer

Author
Nancy A Dawson, MD
Section Editors
Nicholas Vogelzang, MD
W Robert Lee, MD, MS, MEd
Jerome P Richie, MD, FACS
Deputy Editor
Michael E Ross, MD

Disclosures

INTRODUCTION — 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.

Some men with newly diagnosed prostate cancer have advanced, or stage IV, prostate cancer. Prostate cancer is advanced if it has spread beyond the prostate gland and the area around the prostate. It is usually treated with a combination of treatments, such as radiation therapy and hormone therapy. 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”.)

More detailed information about prostate cancer is available by subscription. (See “Overview of treatment for advanced 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”, section on ‘Treatment of rising PSA’.)

STAGE IV (METASTATIC) PROSTATE CANCER TREATMENT — Androgen deprivation therapy (ADT) is usually recommended as the first treatment for men with metastatic prostate cancer.

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. (See “Initial hormone therapy for metastatic prostate cancer”.) The medicines used in this context have the same effect as surgery, as they are a form of “chemical castration”.

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 six 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 (Eulexin) and bicalutamide (Casodex).
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)
Hot flashes
Enlargement of the breasts (called gynecomastia) (see “Patient information: Gynecomastia (breast enlargement in men)”)
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”)
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 “Managing the 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 “Second-line hormone therapy for metastatic 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 (flutamide, nilutamide, bicalutamide) 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.
Chemotherapy — Eventually, most men with advanced prostate cancer stop responding to all forms of hormone treatment. The next step in treatment depends on your situation and your preferences and 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). 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
Abiraterone — Abiraterone (Zytiga) is a new 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 patients who have had progressive disease after treatment 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 “Abiraterone and newer antiandrogen compounds for castrate resistant metastatic prostate cancer”, section on ‘Abiraterone’.)

Immunotherapy — A newer approach to treat advanced prostate cancer uses a cancer vaccine (sipuleucel-T; 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 metastatic prostate cancer”, section on ‘Sipuleucel-T’.)

Side effects with this cancer vaccine have generally been mild and include chills, fever, fatigue, nausea, and headache.

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 “Assessment and management of bone metastases in advanced prostate cancer”.)

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.

CLINICAL TRIALS — 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:

www.cancer.gov/clinicaltrials/learning/
www.cancer.gov/clinicaltrials/
file://clinicaltrials.gov/
WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem.

 

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:

Patient information: Prostate cancer treatment; stage I to III cancer
Patient information: Gynecomastia (breast enlargement in men)
Patient information: Osteoporosis prevention and treatment

Professional Level Information:

Clinical presentation, diagnosis, and staging of prostate cancer
Cryotherapy for prostate cancer
Management of prostate cancer patients with positive regional lymph nodes
Overview of treatment for advanced prostate cancer
Overview of treatment for clinically localized prostate cancer
Radical prostatectomy for localized prostate cancer
Rising serum PSA after radiation therapy for localized prostate cancer: Salvage local therapy
Rising serum PSA after treatment for localized prostate cancer: Systemic therapy
Rising serum PSA following local therapy for prostate cancer: Definition, natural history, and risk stratification
Rising serum PSA following local therapy for prostate cancer: Diagnostic evaluation
Initial hormone therapy for metastatic prostate cancer
Managing the side effects of androgen deprivation therapy
Second-line hormone therapy for metastatic prostate cancer
Chemotherapy in castrate-resistant prostate cancer
Assessment and management of bone metastases in advanced prostate cancer

The following organizations also provide reliable health information.

National Cancer Institute
1-800-4-CANCER
(www.cancer.gov/cancertopics/types/prostate)

National Comprehensive Cancer Network
(file://www.nccn.org/index.asp)

National Library of Medicine
(www.nlm.nih.gov/medlineplus/prostatecancer.html)

Patient support — There are a number of online forums where patients can find information and support from other people with similar conditions.

About.com Cancer Forum
(file://cancer.about.com/forum)

REFERENCES
Loblaw DA, Virgo KS, Nam R, et al. Initial hormonal management of androgen-sensitive metastatic, recurrent, or progressive prostate cancer: 2006 update of an American Society of Clinical Oncology practice guideline. J Clin Oncol 2007; 25:1596.
Winquist E, Waldron T, Berry S, et al. Nonhormonal systemic therapy in men with hormone-refractory prostate cancer: A Clinical Practice Guideline, 2005 www.cancercare.on.ca/pdf/pebc3-15s.pdf (Accessed on April 18, 2011).
Basch EM, Somerfield MR, Beer TM, et al. American Society of Clinical Oncology endorsement of the Cancer Care Ontario Practice Guideline on nonhormonal therapy for men with metastatic hormone-refractory (castration-resistant) prostate cancer. J Clin Oncol 2007; 25:5313.
Chang SS, Benson MC, Campbell SC, et al. Society of Urologic Oncology position statement: redefining the management of hormone-refractory prostate carcinoma. Cancer 2005; 103:11.