What is Advanced Prostate Cancer?

People can mean a lot of different things when they say they have "advanced" prostate cancer. They can mean that their prostate cancer has spread outside of the prostate but only to tissue near the prostate (like seminal vesicles). Prostate cancer that has not spread far can be called "locally advanced prostate cancer."

If you have localized or "locally advanced" prostate cancer, there are other treatments available.

This article is not for you if you want to learn about initial treatments for men with "locally advanced" cancer. These men may be offered therapies that are not covered in this article such as:

•    Surgery to remove the prostate (prostatectomy) and nearby tissue,
•    Cryotherapy
•    Brachytherapy

Please visit our Prostate Cancer article to learn about these types of treatments.

This article is for men with metastatic and castrate-resistant prostate cancer.

The focus of this article is on treatments for prostate cancer that has:

•    Spread far from the prostate (metastatic prostate cancer)
•    Shown signs of growing after using hormone therapy (castrate-resistant prostate cancer or CRPC)

Metastatic prostate cancer

Prostate cancer is metastatic if it has spread to: 

•    Bones 
•    Lungs
•    Liver
•    Brain 
•    Lymph nodes outside the pelvis
•    Other organs

You may be diagnosed with metastatic prostate cancer when you are first diagnosed, after having completed your first treatment or even many years later. It is uncommon to be diagnosed with metastatic prostate cancer on first diagnosis, but it does happen.

Castrate-resistant prostate cancer (CRPC)

Castrate-resistant prostate cancer (CRPC) is when your PSA has risen or your cancer has shown other signs of growing after using hormone therapy. At first, prostate cancer usually responds to hormone treatments. But eventually cancer cells "outsmart" the treatment. They learn how to grow even without testosterone to fuel its growth.

Metastatic castrate-resistant prostate cancer (mCRPC)

If your PSA has risen while on hormone therapy and your cancer has spread far from the prostate, you have metastatic castrate-resistant prostate cancer or mCRPC. Many of the newest treatments available are for men with mCRPC.

Biochemical recurrence

If your PSA has risen after initial treatment but you have no other sign of cancer, you have "biochemical recurrence." The hormone therapy section of this article will help you understand treatments available to you.

Treatment offers hope for extending the quality and length of life

Metastatic prostate cancer, CRPC and mCRPC are not "curable." However, recent treatment advances offer new hope. New treatments can extend the quality and length of life for men with these kinds of advanced prostate cancer.



What are the Symptoms of Advanced Prostate Cancer?

Men with advanced prostate cancer often have no symptoms. Advanced prostate cancer can be found by x-rays or tests done for other medical reasons. When there are symptoms, they depend on the size of the new growth and where the cancer has spread. For example, when prostate cancer has spread to the pelvic bones, you may feel lower back or hip pain. You may have no symptoms from cancer in the prostate. Or you may have problems urinating or see blood in your urine. When men do have symptoms, they often feel tired or weak, have lost weight, feel pain or have shortness of breath.

How can advanced cancer affect your life?

Cancer that has spread far from the prostate cannot be cured. Treatment slows the cancer's growth and controls symptoms. This can help you feel good, extend your life and enjoy life for as long as possible.



What Causes Advanced Prostate Cancer?

Prostate cancer spreads when cancer cells break free from the prostate. These cells enter the blood or lymph nodes. Most cancer cells that break free from the prostate die. But sometimes they spread to other organs and start new tumors. Advanced prostate cancer often moves into the bones before spreading to other organs. Sometimes it spreads to the lungs or liver. It can also spread to the brain.



How is Advanced Prostate Cancer Diagnosed?

To diagnose advanced cancer, your health care provider looks for cancer outside the prostate. Blood and imaging tests may show where the cancer has spread. Your health care provider will want to know how much cancer there is and how it is affecting you. That way they can offer treatment that is best for you.

Advanced cancer may be found before, at the same time, or later than the main tumor. Most men diagnosed with advanced prostate cancer have had biopsy and treatment in the past. When a new tumor is found in someone who has been treated for cancer in the past, it is usually cancer that has spread. Rarely, a bone marrow test, spinal tap or fluid test may also show cancer cells.

If you need a prostate biopsy

Men diagnosed with advanced prostate cancer from the beginning may start with a prostate biopsy. This is a tissue sample taken from your prostate. The biopsy removes small pieces of prostate tissue to look for cancer.

Prostate biopsy is best done with ultrasound and a probe. Before the biopsy, you will have an enema to clean out your bowels and take an antibiotic. During the biopsy, you lie on your side and the probe goes into the rectum.

First, your health care provider takes a picture of the prostate using ultrasound. The prostate gland size, shape and any abnormalities are noted. Shadows are a common abnormality. Shadows might be prostate cancer. But not all shadows are cancer. And not all cancers can be seen.

Prostate biopsy

Prostate biopsy
© 2005 Terese Winslow, U.S. Govt. has certain rights

The prostate gland is then numbed through the probe. Then 10 or more samples of prostate tissue about 3/4 inch long and 1/16 inch wide are removed. The number depends on the size of the prostate gland, PSA test results, and past biopsies.

The biopsy takes 10 to 20 minutes. A pathologist (a doctor who identifies diseases by looking at them under a microscope) looks at the prostate tissue to see if cancer is there. If cancer is seen, the pathologist will also "grade" the tumor.

After a biopsy, you may have blood in your ejaculate and urine. This stops within a few days for urine and a few weeks for semen. About 1 or 2 in 100 men have high fever after biopsy. You will need to take antibiotics for at least 48 hours after the biopsy.

 



How is Advanced Prostate Cancer Staged?

Grading

If the biopsy finds cancer, the pathologist gives it a grade. The grade is a measure of how quickly the tumor is likely to grow and spread. The most common grading system is called the Gleason score. Scores go from 2 to 10. To find a tumor's grade, the pathologist scores each bit of tissue from the biopsy. The pathologist then adds the two most common scores together. This is the Gleason score. A score of 2 to 4 shows low aggressiveness. But scores these low are almost never seen.

The lowest score found is usually 5. That is the least aggressive score most men can get. A Gleason score of 6 is more aggressive. Gleason 7 tumors show even higher aggressiveness. There are two types of these scores. A 4+3 tumor is more aggressive than a 3+4 tumor. That's because more of the higher aggressive grade tumor was found. Gleason 8, 9 and 10 tumors are the most aggressive. They usually have already spread by the time they are found. Talk to your health care provider about your Gleason score.

The Gleason Scale

Staging

Tumor stage shows the size and spread of the cancer. Cancer in only a small part of the prostate is more treatable than cancer that has spread all through it. Tumors found only in the prostate are more successfully treated than those that have metastasized (spread) outside the prostate. Tumors that have spread to places far from the prostate, like to lymph nodes or bone, have the poorest results.

Tumor, Nodes and Metastasis (TNM) is the system used for tumor staging.

Tumor, Nodes and Metastasis (TNM)

Using the "T" part of the system, prostate cancer is staged as:

  • T1: Health care provider cannot feel the tumor
  • T1a: Cancer present in less than 5% of the tissue removed and low grade (Gleason < 6)
  • T1b: Cancer present in more than 5% of the tissue removed or is of a higher grade (Gleason > 6)
  • T1c: Cancer found by needle biopsy done because of a high PSA
  • T2: Health care provider can feel the tumor with a DRE but the tumor is confined to prostate
  • T2a: Cancer found in one half or less of one side (left or right) of the prostate
  • T2b: Cancer found in more than half of one side (left or right) of the prostate
  • T2c: Cancer found in both sides of the prostate
  • T3: Cancer has begun to spread outside the prostate and may involve the seminal vesicles
  • T3a: Cancer extends outside the prostate but not to the seminal vesicles
  • T3b: Cancer has spread to the seminal vesicles
  • T4: Cancer has spread to nearby organs such as the urethral sphincter, rectum, bladder, or pelvis wall
  • N0 stage, there is no sign of the cancer moving to the lymph nodes in the area of the prostate.
  • M0 stage, there is no sign of tumor metastasis.
  • If the cancer is spreading to the lymph node or if the tumor has spread to other parts of the body, the stage is changed. It becomes either N1, for node, and/or M1, for metastasis.

Prostate Cancer Stage Groupings

Imaging Tests

Prostate cancer staging
Prostate cancer staging
© 2010 Terese Winslow, U.S. Govt. has certain rights

Prostate cancer usually spreads from the prostate into nearby tissues. Then it can spread to the seminal vesicles, lymph nodes, bones, lungs, and other organs. Your doctor may want imaging tests to see how far your cancer has spread. These include a pelvic CT, MRI or a bone scan.

Hope for advanced prostate cancer?

There is no cure for advanced prostate cancer. About 27,500 deaths from prostate cancer are predicted in the U.S. this year. But advances in science mean cancer growth can be slowed. Treatment can also reduce cancer-related symptoms so you feel better. New therapies are improving survival and quality of life, especially for men with no cancer-related pain.



What are the Treatments for Advanced Prostate Cancer?

The goal of treatment depends on how far the cancer has spread. With advanced cancer, the goal is to relieve symptoms and help you live longer. The most common types of therapy are:



Hormone Therapy

What is hormone therapy?

Hormone therapy is any treatment that lowers the man's androgen (male sex hormone) levels. For prostate cancer, it is any method to block testosterone. Because testosterone is the main fuel for prostate cancer cells, blocking it may slow the cancer.

There are several types of hormone therapy. Some treat prostate cancer that has spread beyond the prostate or is advanced.

Some health care providers may use other types of hormone therapy for earlier stage prostate cancer. Hormone therapy can shrink a local tumor to allow more effective radiation treatment. This helps with more aggressive localized cancer. Types of hormone therapy include:

  • Surgery to remove the testicles (Orchiectomy)
  • LHRH or GnRH agonists
  • LHRH or GnRH antagonists
  • CAB/anti-androgens
  • Estrogen therapy

Who are good candidates for hormone therapy?

Men whose prostate cancer has metastasized (spread) outside the prostate are good candidates for hormone therapy. It is also used when prostate cancer has come back after surgery or radiation treatments.

What are the benefits, risks and side effects of hormone therapy?

Because hormone therapy can be used as cancer advances, this therapy is useful for cancer that has returned. But hormone therapy usually works for only a few years. Over time, the cancer can grow in spite of the low hormone level. Hormone therapy does not cure the cancer. It has side effects. And other treatments are often needed to manage the cancer.

Before starting any type of hormone therapy, talk with your health care provider. Learn about the effects of testosterone loss. Low dose or intermittent (not constant) hormone therapy may lessen side effects.

Possible side effects include:

  • Lower libido (sexual desire) in 90% of men

  • Erectile dysfunction (inability to have or keep a strong enough erection for sex)

  • Hot flashes (sudden spread of warmth to the face, neck and upper body, heavy sweating). Hot flashes are not a health risk. Medicines can control them.

  • Weight gain of 10 to 15 pounds. Diet, lower carbohydrate intake and exercise can help.

  • Mood swings

  • Depression caused by the treatment, reaction to side effects, or other cancer-related issues. Symptoms include loss of hope and loss of interest in usually enjoyable activities. Other symptoms include not being able to concentrate and changes in appetite and sleeping.

  • Fatigue (tiredness) that doesn't go away with rest or sleep, caused by lower testosterone

  • Anemia (low red blood cell count). Less oxygen gets to tissues and organs, causing tiredness or weakness. It can be treated with medicines, vitamins and minerals.

  • Loss of muscle mass. This may cause weakness or low strength. Progressive weight-bearing exercise help improve strength.

  • Osteoporosis (loss of bone mineral density). This means bones become thinner, brittle and break easier. It can be treated with medicines, calcium and vitamin D. Progressive weight-bearing exercise help strengthen bones.

  • Memory loss

  • High cholesterol, especially LDL ("bad") cholesterol

  • Breast nipple tenderness

  • Increased risk of diabetes, 40% higher compared to men not on ADT

  • Heart disease. Some studies show men on ADT are at higher risk for heart problems. Others have not shown this. The effect of ADT on the heart is still unknown.

What is orchiectomy?

Orchiectomy Orchiectomy is surgery to remove the testicles. It is also called castration. The testicles make most of the body's testosterone. Orchiectomy is a type of hormone therapy because removing the testicles stops the body from making the male hormone, testosterone.

Orchiectomy is surgery to remove the testicles. It is also called castration. The testicles make most of the body's testosterone. Orchiectomy is a type of hormone therapy because removing the testicles stops the body from making the male hormone, testosterone.

Orchiectomy is fairly simple surgery. It is usually done as an outpatient. It may be done with local or general anesthetic. The surgeon makes a small cut in the scrotum (sac that holds the testicles). The testicles are detached from blood vessels and removed. The vas deferens (tube that carries sperm to the prostate before ejaculation) is removed. Then the sac is sewn up.

What are the benefits, risks and side effects of orchiectomy?

It is not expensive. It is simple and has few risks. It only needs to be performed once. It is effective right away. Testosterone levels drop dramatically. There is often fast relief from cancer symptoms.

The main risks are infection and bleeding. Death is a risk of all surgery with general anesthesia. But death is extremely rare with castration. Many men are very uncomfortable with this surgery because it is not reversible. Concerns about body image or self-image may lead men to choose another treatment.

Removing the testicles means the body stops making testosterone. This causes the side effects listed above for hormone therapy. Castration may also have a psychological effect. The look of the genital area and lack of testicles may affect self-image. Some men choose to have artificial testicles or saline implants placed in the scrotum. This makes the scrotum look the same as before surgery.

Another surgery choice is subcapsular orchiectomy. This removes the glands around the testicles. But it leaves the testicles themselves. The scrotum looks normal.

Who are good candidates for orchiectomy?

Men who choose this therapy want a one-time surgical treatment. They must be healthy enough to have surgery. And they must be willing to have their testicles permanently removed.

LHRH or GnRH agonists and antagonists

These are the first and second treatment choices for localized cancer and cancer that has come back.

LHRH or GnRH agonists

This hormone therapy is usually the first treatment for localized cancer. It is also used for cancer that has come back, whether or not it has spread. Possible agonists used include:

  • Lupron (Leuprolide)
  • Zoladex (Goserelin)
  • Trelstar (Triptorelin)
  • Vantas (Histrelin)

LHRH or GnRH agonists are man-made, powerful versions of natural LHRH hormone. Your body makes natural LHRH in your hypothalamus. LHRH causes your body to make luteinizing hormone (LH). LH then causes your body to make testosterone.

With LHRH therapy, you are given man-made LHRH. Your body then makes more LH. Testosterone levels rise. Your prostate and prostate cancer cells grow, causing bone pain. This is called a "flare up." It lasts 7-10 days. Your body then stops making any new natural LHRH. That causes your body to stop making new LH and testosterone.

Your testosterone levels drop by 90-95%. This is called the "castrate level." It's the same as if your testicles were gone. Once testosterone levels drop, prostate cells and cancer cells stop growing. This is because testosterone is not fueling their growth.

LHRH or GnRH antagonists

This is the second line of treatment for localized cancer or cancer that has come back. LHRH or GnRH antagonists interfere with brain signals. This blocks the release of natural LH. When LH isn't released, your body stops making testosterone. The drug used is Firmagon (degarelix).

Antagonists usually do not produce the hormonal "flare up" seen often with agonists. There is no short-term testosterone boost when you begin this therapy.

Antagonists are injected (shot) in the buttocks every month. It is done in the health care provider's office. You will stay in the office awhile after the shot. This is to make sure there is no allergic reaction. After the first shot, a blood test makes sure testosterone levels have dropped. You may also have tests to monitor bone density.

What are the benefits, risks and side effects of LHRH or GnRH treatment?

With LHRH treatment you must go to your health care provider every month or two for injections. Your health care provider will also need to check side effects and PSA levels. The PSA test will tell if the cancer has slowed.

With LHRH treatment there is no need for an orchiectomy (surgery). Side effects may be reversible. This depends on the length of time you are on treatment.

The main disadvantage to LHRH treatment is the cost. The injections together are more expensive than a one-time surgery. The cost may be a burden if health insurance does not cover the treatment.

Side effects include the "flare up" from the agonist treatment, bone pain and possible irreversible loss of the body's ability to make testosterone.

Who are good candidates for LHRH treatment?

Men who cannot or do not wish to have surgical removal of the testicles are good candidates for these treatments.

Combined androgen blockade (CAB)/anti-androgen therapy

This treatment is only used when first line LHRH agonist and LHRH antagonist treatment did not work. Or the drugs are not working by themselves. It is used for castrate resistant prostate cancer that is non-metastatic (is not spreading).

What is combined androgen blockade (CAB)/anti-androgen therapy?

This treatment combines castration and anti-androgen therapy. Castration is either by surgery or by using hormones to stop your body from making testosterone.

The treatment stops testosterone by blocking the androgen receptors in the prostate cells. Normally, testosterone would bind with these receptors. This fuels growth of prostate cancer cells. With the receptors blocked, testosterone cannot "feed" the prostate. Anti-androgen therapy does not lower testosterone. So it may have fewer or milder side effects than surgery and medical hormone treatment.

These are the three most common anti-androgen drugs used as second line treatment for non-metastatic prostate cancer growth:

  • Flutamide (Eulexin)

  • Bicalutamide (Casodex)

  • Nilutamide (Nilandvon)

The drug is taken as a tablet or pill. A single dose usually has 50 mg to 150 mg. You should take the drug around the same time every day. This keeps a steady level of the drug in your body. If you forget to take a dose you should not take a double dose. Taking a dose the same time each day also lowers side effects like nausea or vomiting.

What are the benefits, risks and side effects of CAB/anti-androgen therapy?

Using anti-androgens a few weeks before LHRH therapy reduces painful and potentially dangerous "flare up." Anti-androgens are also used after surgery or castration when hormones stops working. A few studies show anti-androgens alone may not work as well as medical or surgical castration alone. Other studies found no difference in survival rates of people who used only one form of treatment.

Who are good candidates for CAB/anti-androgen therapy?

You and your doctor will weigh the benefits and risks of this therapy against other treatments. Whether this therapy is a good choice for you depends partly on where the cancer has spread and its effects.

What is estrogen hormone therapy?

Estrogens are female sex hormones. They can be used to block testosterone production in the testicles.

What are the risks, benefits and side effects of estrogen hormones?

Estrogen hormone therapy has side effects similar to androgen hormone therapy. But the use of estrogens may cause female sex characteristics to develop. This may include breast tenderness and swelling and other changes.

Who are good candidates for estrogen hormone therapy?

Because of the side effects of estrogen hormone therapy, it is not often used today.

New hormone therapies for mCPRC, advanced prostate cancer that has metastasized (spread)

Scientists have made new discoveries in how to treat metastatic CRPC (mCRPC). There are new treatments for mCRPC. And changes are being made to make existing treatments work better.

If you are diagnosed with mCRPC, your health care provider may prescribe one of these treatments to help you. Treatments may help you delay symptoms and live longer:

Androgen synthesis inhibitors

Abiraterone acetate (Zytiga®) is a drug you take as a pill. It stops your body and the cancer from making steroids (including testosterone). Because of the way it works, this drug must be taken with an oral steroid called Prednisone. Abiraterone may be used before or after chemotherapy in men with mCRPC.

Androgen receptor binding inhibitors

Enzalutamide (Xtandi®) is a drug that blocks testosterone from binding to the prostate cancer cells. Because it works differently than Abiraterone , you do not need to take a steroid with this drug. It is taken as a pill. Enzalutamide (Xtandi®) may be used in men with mCRPC before or after chemotherapy.



Immunotherapy

This therapy is for those with metastatic prostate cancer (mCRPC) and no symptoms.

What is immunotherapy?

Researchers are now using the body's own immune system to treat mCPRC. If prostate cancer returns despite hormone therapy and is metastatic, your health care provider may offer Sipuleucel-T (Provenge®).

Sipuleucel-T works by boosting your immune system so it attacks cancer cells. Other prostate cancer immunotherapies are also being studied.

What are the benefits, risks and side effects of immunotherapy?

Immunotherapy boosts the immune system. It may extend survival by months for some patients. This is the first immunotherapy that has been shown to help men with prostate cancer live longer.

Side effects may include fever, chills, weakness, headache, nausea, vomiting and diarrhea. The patient may also have low blood pressure and rashes.

Who are good candidates for immunotherapy?

Immunotherapy is given to mCRPC patients before chemotherapy. There may also be patients who get chemotherapy and immunotherapy together. For immunotherapy, the patient needs to have no or mild symptoms. If chemotherapy was started before symptoms or chemotherapy causes symptoms to go away, immunotherapy is a possible choice.



Bone-targeted Therapy

If you have advanced prostate cancer or are taking hormonal therapy, your provider may suggest calcium or Vitamin D for your bones. Some drugs can also help strengthen and protect your bones. These include Denosumab (Xgeva®) and Zoledronic Acid (Zometa®). Both help prevent bad side effects from the cancer growing in your bones. These side effects can include bone thinning, bone breaks and bone pain. 

Radium-223 (Xofigo®) is another new treatment approved for men whose mCPRC has spread to their bones. This treatment is injected in your veins. It collects in the bones where cancer has spread and is growing fast.

Once in the bones it gives off small amounts of radiation that can only travel short distances. This can target radiation to the exact areas of the bone where cancer cells are growing. Radium-223 has been shown to help men live longer.

With Radium-223, your PSA level does not show how well you are responding. Although your PSA level may increase, this does not mean that the treatment is not working. 



Chemotherapy

Chemotherapy is another treatment choice for men with metastatic CRPC (mCRPC).

What is chemotherapy?

Chemotherapy drugs slow the growth of cancer and reduce symptoms. Most of the drugs are given into the vein (intravenous, IV). Chemotherapy does not cure mCRPC. It can ease the pain from prostate cancer, shrink tumors and lower levels of PSA. Studies show that many chemotherapy drugs can affect prostate cancer.

Some, such as Docetaxel (Taxotere®, DocefrezTM) and Cabazitaxel (Jevtana®) have been shown to help men live longer. Scientists are studying other new chemotherapy drugs and mixtures of drugs.

Drugs circulate in the blood during chemotherapy. They kill any rapidly growing cells, both cancer and non-cancer cells. Often, chemotherapy is not the main therapy for prostate cancer. But it is a useful treatment for men whose cancer has spread and are still repsonding to hormone therapy (hormone sensitive).

Chemotherapy is standard for prostate cancer that has spread and is progressing despite low levels of testosterone. New data suggest that when combined with hormone therapy, it may also improve survival for men whose cancer has spread.

In 2004, two studies showed that chemotherapy could extend survival. This was in men whose mCRPC no longer responded to hormone therapy. The FDA approved Docetaxel for use with Prednisone. It is the first registered treatment for patients with mCRPC. The combination therapy has extended survival by several months.

A drug called Cabazitaxel is also approved for the treatment of mCRPC. When men who have received Docetaxel have progression of their cancer, Cabazitaxel may slow the cancer growth. 

What are the benefits, risks and side effects of chemotherapy?

The decision to start chemotherapy is a difficult and personal one. It is based on:

  • What other treatments or clinical trials are available.
  • How well chemotherapy is likely to be tolerated.
  • What other therapies have been tried.
  • Whether radiation is needed to relieve pain quickly.

Often chemotherapy is given before pain starts. The goal is to prevent pain as cancer spreads to bones and other sites.

Chemotherapy may improve survival. It may prevent pain. Side effects include fatigue, nausea, vomiting and hair loss. There can be changes in your sense of taste. There may also be a decrease in blood cells. This may lead to a risk of infections. Chemotherapy drugs are monitored closely. There are medicines to lessen side effects. Most side effects stop once chemotherapy ends.

Who are good candidates for chemotherapy?

Chemotherapy is useful for men whose cancer is widespread. It can relieve symptoms. It can even prolong life for some men with advanced prostate cancer.



Radiation

If cancer has spread far from your prostate, your health care provider may suggest radiation. Prostate cancer often spreads to the bones. Radiation can help ease pain caused by cancer spreading to the bone. It can ease other symptoms.

The radiation is most often given in one or a few visits. The treatment is like having an x-ray. It uses high-energy beams to kill tumors. New radiation techniques focus on cancer cells while saving nearby healthy tissue. Many use computers to map the prostate. They target radiation just where it is needed. New software allows better planning and targeting of radiation doses.

These methods are expected to improve the success of radiation therapy. And they reduce side effects. Studies are being done to find out which radiation methods are best for which men.



Hormone Therapy

What is hormone therapy?

Hormone therapy is any treatment that lowers the man's androgen (male sex hormone) levels. For prostate cancer, it is any method to block testosterone. Because testosterone is the main fuel for prostate cancer cells, blocking it may slow the cancer.

There are several types of hormone therapy. Some treat prostate cancer that has spread beyond the prostate or is advanced.

Some health care providers may use other types of hormone therapy for earlier stage prostate cancer. Hormone therapy can shrink a local tumor to allow more effective radiation treatment. This helps with more aggressive localized cancer. Types of hormone therapy include:

  • Surgery to remove the testicles (Orchiectomy)
  • LHRH or GnRH agonists
  • LHRH or GnRH antagonists
  • CAB/anti-androgens
  • Estrogen therapy

Who are good candidates for hormone therapy?

Men whose prostate cancer has metastasized (spread) outside the prostate are good candidates for hormone therapy. It is also used when prostate cancer has come back after surgery or radiation treatments.

What are the benefits, risks and side effects of hormone therapy?

Because hormone therapy can be used as cancer advances, this therapy is useful for cancer that has returned. But hormone therapy usually works for only a few years. Over time, the cancer can grow in spite of the low hormone level. Hormone therapy does not cure the cancer. It has side effects. And other treatments are often needed to manage the cancer.

Before starting any type of hormone therapy, talk with your health care provider. Learn about the effects of testosterone loss. Low dose or intermittent (not constant) hormone therapy may lessen side effects.

Possible side effects include:

  • Lower libido (sexual desire) in 90% of men

  • Erectile dysfunction (inability to have or keep a strong enough erection for sex)

  • Hot flashes (sudden spread of warmth to the face, neck and upper body, heavy sweating). Hot flashes are not a health risk. Medicines can control them.

  • Weight gain of 10 to 15 pounds. Diet, lower carbohydrate intake and exercise can help.

  • Mood swings

  • Depression caused by the treatment, reaction to side effects, or other cancer-related issues. Symptoms include loss of hope and loss of interest in usually enjoyable activities. Other symptoms include not being able to concentrate and changes in appetite and sleeping.

  • Fatigue (tiredness) that doesn't go away with rest or sleep, caused by lower testosterone

  • Anemia (low red blood cell count). Less oxygen gets to tissues and organs, causing tiredness or weakness. It can be treated with medicines, vitamins and minerals.

  • Loss of muscle mass. This may cause weakness or low strength. Progressive weight-bearing exercise help improve strength.

  • Osteoporosis (loss of bone mineral density). This means bones become thinner, brittle and break easier. It can be treated with medicines, calcium and vitamin D. Progressive weight-bearing exercise help strengthen bones.

  • Memory loss

  • High cholesterol, especially LDL ("bad") cholesterol

  • Breast nipple tenderness

  • Increased risk of diabetes, 40% higher compared to men not on ADT

  • Heart disease. Some studies show men on ADT are at higher risk for heart problems. Others have not shown this. The effect of ADT on the heart is still unknown.

What is orchiectomy?

Orchiectomy Orchiectomy is surgery to remove the testicles. It is also called castration. The testicles make most of the body's testosterone. Orchiectomy is a type of hormone therapy because removing the testicles stops the body from making the male hormone, testosterone.

Orchiectomy is surgery to remove the testicles. It is also called castration. The testicles make most of the body's testosterone. Orchiectomy is a type of hormone therapy because removing the testicles stops the body from making the male hormone, testosterone.

Orchiectomy is fairly simple surgery. It is usually done as an outpatient. It may be done with local or general anesthetic. The surgeon makes a small cut in the scrotum (sac that holds the testicles). The testicles are detached from blood vessels and removed. The vas deferens (tube that carries sperm to the prostate before ejaculation) is removed. Then the sac is sewn up.

What are the benefits, risks and side effects of orchiectomy?

It is not expensive. It is simple and has few risks. It only needs to be performed once. It is effective right away. Testosterone levels drop dramatically. There is often fast relief from cancer symptoms.

The main risks are infection and bleeding. Death is a risk of all surgery with general anesthesia. But death is extremely rare with castration. Many men are very uncomfortable with this surgery because it is not reversible. Concerns about body image or self-image may lead men to choose another treatment.

Removing the testicles means the body stops making testosterone. This causes the side effects listed above for hormone therapy. Castration may also have a psychological effect. The look of the genital area and lack of testicles may affect self-image. Some men choose to have artificial testicles or saline implants placed in the scrotum. This makes the scrotum look the same as before surgery.

Another surgery choice is subcapsular orchiectomy. This removes the glands around the testicles. But it leaves the testicles themselves. The scrotum looks normal.

Who are good candidates for orchiectomy?

Men who choose this therapy want a one-time surgical treatment. They must be healthy enough to have surgery. And they must be willing to have their testicles permanently removed.

LHRH or GnRH agonists and antagonists

These are the first and second treatment choices for localized cancer and cancer that has come back.

LHRH or GnRH agonists

This hormone therapy is usually the first treatment for localized cancer. It is also used for cancer that has come back, whether or not it has spread. Possible agonists used include:

  • Lupron (Leuprolide)
  • Zoladex (Goserelin)
  • Trelstar (Triptorelin)
  • Vantas (Histrelin)

LHRH or GnRH agonists are man-made, powerful versions of natural LHRH hormone. Your body makes natural LHRH in your hypothalamus. LHRH causes your body to make luteinizing hormone (LH). LH then causes your body to make testosterone.

With LHRH therapy, you are given man-made LHRH. Your body then makes more LH. Testosterone levels rise. Your prostate and prostate cancer cells grow, causing bone pain. This is called a "flare up." It lasts 7-10 days. Your body then stops making any new natural LHRH. That causes your body to stop making new LH and testosterone.

Your testosterone levels drop by 90-95%. This is called the "castrate level." It's the same as if your testicles were gone. Once testosterone levels drop, prostate cells and cancer cells stop growing. This is because testosterone is not fueling their growth.

LHRH or GnRH antagonists

This is the second line of treatment for localized cancer or cancer that has come back. LHRH or GnRH antagonists interfere with brain signals. This blocks the release of natural LH. When LH isn't released, your body stops making testosterone. The drug used is Firmagon (degarelix).

Antagonists usually do not produce the hormonal "flare up" seen often with agonists. There is no short-term testosterone boost when you begin this therapy.

Antagonists are injected (shot) in the buttocks every month. It is done in the health care provider's office. You will stay in the office awhile after the shot. This is to make sure there is no allergic reaction. After the first shot, a blood test makes sure testosterone levels have dropped. You may also have tests to monitor bone density.

What are the benefits, risks and side effects of LHRH or GnRH treatment?

With LHRH treatment you must go to your health care provider every month or two for injections. Your health care provider will also need to check side effects and PSA levels. The PSA test will tell if the cancer has slowed.

With LHRH treatment there is no need for an orchiectomy (surgery). Side effects may be reversible. This depends on the length of time you are on treatment.

The main disadvantage to LHRH treatment is the cost. The injections together are more expensive than a one-time surgery. The cost may be a burden if health insurance does not cover the treatment.

Side effects include the "flare up" from the agonist treatment, bone pain and possible irreversible loss of the body's ability to make testosterone.

Who are good candidates for LHRH treatment?

Men who cannot or do not wish to have surgical removal of the testicles are good candidates for these treatments.

Combined androgen blockade (CAB)/anti-androgen therapy

This treatment is only used when first line LHRH agonist and LHRH antagonist treatment did not work. Or the drugs are not working by themselves. It is used for castrate resistant prostate cancer that is non-metastatic (is not spreading).

What is combined androgen blockade (CAB)/anti-androgen therapy?

This treatment combines castration and anti-androgen therapy. Castration is either by surgery or by using hormones to stop your body from making testosterone.

The treatment stops testosterone by blocking the androgen receptors in the prostate cells. Normally, testosterone would bind with these receptors. This fuels growth of prostate cancer cells. With the receptors blocked, testosterone cannot "feed" the prostate. Anti-androgen therapy does not lower testosterone. So it may have fewer or milder side effects than surgery and medical hormone treatment.

These are the three most common anti-androgen drugs used as second line treatment for non-metastatic prostate cancer growth:

  • Flutamide (Eulexin)

  • Bicalutamide (Casodex)

  • Nilutamide (Nilandvon)

The drug is taken as a tablet or pill. A single dose usually has 50 mg to 150 mg. You should take the drug around the same time every day. This keeps a steady level of the drug in your body. If you forget to take a dose you should not take a double dose. Taking a dose the same time each day also lowers side effects like nausea or vomiting.

What are the benefits, risks and side effects of CAB/anti-androgen therapy?

Using anti-androgens a few weeks before LHRH therapy reduces painful and potentially dangerous "flare up." Anti-androgens are also used after surgery or castration when hormones stops working. A few studies show anti-androgens alone may not work as well as medical or surgical castration alone. Other studies found no difference in survival rates of people who used only one form of treatment.

Who are good candidates for CAB/anti-androgen therapy?

You and your doctor will weigh the benefits and risks of this therapy against other treatments. Whether this therapy is a good choice for you depends partly on where the cancer has spread and its effects.

What is estrogen hormone therapy?

Estrogens are female sex hormones. They can be used to block testosterone production in the testicles.

What are the risks, benefits and side effects of estrogen hormones?

Estrogen hormone therapy has side effects similar to androgen hormone therapy. But the use of estrogens may cause female sex characteristics to develop. This may include breast tenderness and swelling and other changes.

Who are good candidates for estrogen hormone therapy?

Because of the side effects of estrogen hormone therapy, it is not often used today.

New hormone therapies for mCPRC, advanced prostate cancer that has metastasized (spread)

Scientists have made new discoveries in how to treat metastatic CRPC (mCRPC). There are new treatments for mCRPC. And changes are being made to make existing treatments work better.

If you are diagnosed with mCRPC, your health care provider may prescribe one of these treatments to help you. Treatments may help you delay symptoms and live longer:

Androgen synthesis inhibitors

Abiraterone acetate (Zytiga®) is a drug you take as a pill. It stops your body and the cancer from making steroids (including testosterone). Because of the way it works, this drug must be taken with an oral steroid called Prednisone. Abiraterone may be used before or after chemotherapy in men with mCRPC.

Androgen receptor binding inhibitors

Enzalutamide (Xtandi®) is a drug that blocks testosterone from binding to the prostate cancer cells. Because it works differently than Abiraterone , you do not need to take a steroid with this drug. It is taken as a pill. Enzalutamide (Xtandi®) may be used in men with mCRPC before or after chemotherapy.



Immunotherapy

This therapy is for those with metastatic prostate cancer (mCRPC) and no symptoms.

What is immunotherapy?

Researchers are now using the body's own immune system to treat mCPRC. If prostate cancer returns despite hormone therapy and is metastatic, your health care provider may offer Sipuleucel-T (Provenge®).

Sipuleucel-T works by boosting your immune system so it attacks cancer cells. Other prostate cancer immunotherapies are also being studied.

What are the benefits, risks and side effects of immunotherapy?

Immunotherapy boosts the immune system. It may extend survival by months for some patients. This is the first immunotherapy that has been shown to help men with prostate cancer live longer.

Side effects may include fever, chills, weakness, headache, nausea, vomiting and diarrhea. The patient may also have low blood pressure and rashes.

Who are good candidates for immunotherapy?

Immunotherapy is given to mCRPC patients before chemotherapy. There may also be patients who get chemotherapy and immunotherapy together. For immunotherapy, the patient needs to have no or mild symptoms. If chemotherapy was started before symptoms or chemotherapy causes symptoms to go away, immunotherapy is a possible choice.



Bone-targeted Therapy

If you have advanced prostate cancer or are taking hormonal therapy, your provider may suggest calcium or Vitamin D for your bones. Some drugs can also help strengthen and protect your bones. These include Denosumab (Xgeva®) and Zoledronic Acid (Zometa®). Both help prevent bad side effects from the cancer growing in your bones. These side effects can include bone thinning, bone breaks and bone pain. 

Radium-223 (Xofigo®) is another new treatment approved for men whose mCPRC has spread to their bones. This treatment is injected in your veins. It collects in the bones where cancer has spread and is growing fast.

Once in the bones it gives off small amounts of radiation that can only travel short distances. This can target radiation to the exact areas of the bone where cancer cells are growing. Radium-223 has been shown to help men live longer.

With Radium-223, your PSA level does not show how well you are responding. Although your PSA level may increase, this does not mean that the treatment is not working. 



Chemotherapy

Chemotherapy is another treatment choice for men with metastatic CRPC (mCRPC).

What is chemotherapy?

Chemotherapy drugs slow the growth of cancer and reduce symptoms. Most of the drugs are given into the vein (intravenous, IV). Chemotherapy does not cure mCRPC. It can ease the pain from prostate cancer, shrink tumors and lower levels of PSA. Studies show that many chemotherapy drugs can affect prostate cancer.

Some, such as Docetaxel (Taxotere®, DocefrezTM) and Cabazitaxel (Jevtana®) have been shown to help men live longer. Scientists are studying other new chemotherapy drugs and mixtures of drugs.

Drugs circulate in the blood during chemotherapy. They kill any rapidly growing cells, both cancer and non-cancer cells. Often, chemotherapy is not the main therapy for prostate cancer. But it is a useful treatment for men whose cancer has spread and are still repsonding to hormone therapy (hormone sensitive).

Chemotherapy is standard for prostate cancer that has spread and is progressing despite low levels of testosterone. New data suggest that when combined with hormone therapy, it may also improve survival for men whose cancer has spread.

In 2004, two studies showed that chemotherapy could extend survival. This was in men whose mCRPC no longer responded to hormone therapy. The FDA approved Docetaxel for use with Prednisone. It is the first registered treatment for patients with mCRPC. The combination therapy has extended survival by several months.

A drug called Cabazitaxel is also approved for the treatment of mCRPC. When men who have received Docetaxel have progression of their cancer, Cabazitaxel may slow the cancer growth. 

What are the benefits, risks and side effects of chemotherapy?

The decision to start chemotherapy is a difficult and personal one. It is based on:

  • What other treatments or clinical trials are available.
  • How well chemotherapy is likely to be tolerated.
  • What other therapies have been tried.
  • Whether radiation is needed to relieve pain quickly.

Often chemotherapy is given before pain starts. The goal is to prevent pain as cancer spreads to bones and other sites.

Chemotherapy may improve survival. It may prevent pain. Side effects include fatigue, nausea, vomiting and hair loss. There can be changes in your sense of taste. There may also be a decrease in blood cells. This may lead to a risk of infections. Chemotherapy drugs are monitored closely. There are medicines to lessen side effects. Most side effects stop once chemotherapy ends.

Who are good candidates for chemotherapy?

Chemotherapy is useful for men whose cancer is widespread. It can relieve symptoms. It can even prolong life for some men with advanced prostate cancer.



Radiation

If cancer has spread far from your prostate, your health care provider may suggest radiation. Prostate cancer often spreads to the bones. Radiation can help ease pain caused by cancer spreading to the bone. It can ease other symptoms.

The radiation is most often given in one or a few visits. The treatment is like having an x-ray. It uses high-energy beams to kill tumors. New radiation techniques focus on cancer cells while saving nearby healthy tissue. Many use computers to map the prostate. They target radiation just where it is needed. New software allows better planning and targeting of radiation doses.

These methods are expected to improve the success of radiation therapy. And they reduce side effects. Studies are being done to find out which radiation methods are best for which men.



More Information

Frequently Asked Questions

How accurate is the PSA test when it comes to remission? Can I trust that a low PSA values means I am disease-free?

Your PSA level may lower after treatment. But a low PSA level does not mean the cancer is cured. If testosterone is undetectable (after surgery) or low and stable (after radiation), it may mean the cancer has stopped. If your PSA is rising, it may mean the cancer is progressing. Or it may not. PSA is produced by all prostate cells, not just prostate cancer cells.

So PSA is not really a marker for the cancer's progress. It is a marker for prostate cell activity. Doctors don't usually look at only one PSA reading. They see how the numbers progress. After surgical removal of the prostate, the PSA level should be undetectable. And after radiation therapy, the PSA should be low, less than 1.0 ng/ml.

The PSA may mean the cancer has come back if the rise is:

  • Above 0.2 after surgery to remove the prostate
  • 2.0 above the lowest level achieved after radiation therapy

In other words, if a man's PSA fell to 0.2 after radiation therapy, then rose to 0.7, 1.1, 1.4, 1.6, and 1.9, he would still be classified as not having prostate cancer even though his PSA is rising. To be classified as having cancer again, the PSA would need to be at 2.2.

The reason doctors use many tests after radiation is that the PSA can "bounce" or "jump up" after radiation therapy. Then it will come back down to its normal level. If doctors rely on one high PSA, they may test during a bounce. The results would be misleading. The PSA bounce usually happens between 12 months and 2 years after the end of therapy.

If the PSA is rising, the doctor might want to start therapy anyway. PSA is only one of many things to consider. The original clinical stage of disease, the Gleason score of the tumor, the PSA before diagnosis, the overall health, and general life expectancy are key factors in the decision. So be prepared to talk about treatment choices even if you don't fit the classical categories for PSA rise after the first treatment.

On the other hand, if your PSA is rising and you do fit the categories above, that doesn't necessarily mean a return of cancer. Researchers have found that PSA cut-offs might not be enough for truly understanding how prostate cancer grows.

What are bones and skeletal related events (SREs)?

Prostate cancer is usually a disease of the aging male. Older men with prostate cancer are at risk for bone and mineral loss. This can lead to bone weakening (osteopenia) and bone loss (osteoporosis). Low testosterone and castration makes this worse. If you have prostate cancer you should take calcium and vitamin D and do weight bearing exercises.

Men with prostate cancer spread to the bones are at risk for "skeletal-related events (SREs)." These include bone fractures and need for surgery to prevent fracture. Two approved medications reduce SREs. Zolendronic Acid helps reduce bone turnover. It has been shown to reduce SRE's in men with CRPC. It is given by IV every three to four weeks. Side effects include low calcium, worsening kidney function and, rarely, destruction of the jaw bone. So, you are monitored closely. You should have a dental exam before starting the drugs.

A second approved drug for SREs is Denosumab. It reduces bone turnover. It is approved for men on hormone therapy and men with CRPC. Doses depend on the disease state. The drug is given under the skin.

In a study comparing denosumab to Zolendronic Acid, Denosumab was slightly better in delaying SRE's. Denosumab also results in low calcium and can, rarely, destroy the jaw, so a dental check before and calcium monitoring after treatment are advised.