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What Happens When Hormone Treatment For Prostate Cancer Stops Working

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Treating Advanced Prostate Cancer

Hormone Therapy for Prostate Cancer

If the cancer has reached an advanced stage, it’s no longer possible to cure it. But it may be possible to slow its progression, prolong your life and relieve symptoms.

Treatment options include:

  • hormone treatment
  • chemotherapy

If the cancer has spread to your bones, medicines called bisphosphonates may be used. Bisphosphonates help reduce bone pain and bone loss.

What Are Male Sex Hormones

Hormones are substances that are made by glands in the body. Hormones circulate in the bloodstream and control the actions of certain cells or organs.

Androgens are a class of hormones that control the development and maintenance of male characteristics. The most abundant androgens in men are testosterone and dihydrotestosterone .

Androgens are required for normal growth and function of the prostate, a gland in the male reproductive system that helps make semen. Androgens are also necessary for prostate cancers to grow. Androgens promote the growth of both normal and cancerous prostate cells by binding to and activating the androgen receptor, a protein that is expressed in prostate cells . Once activated, the androgen receptor stimulates the expression of specific genes that cause prostate cells to grow .

Almost all testosterone is produced in the testicles a small amount is produced by the adrenal glands. Although prostate cells do not normally make testosterone, some prostate cancer cells acquire the ability to do so .

Options In Hormone Therapy

Testosterone levels in the body can be reduced either surgically or with drugs. The surgical option is castration, achieved by removing the testicles during a bilateral orchiectomy. Once the only option, it has since been supplanted by drugs that lower testosterone levels to amounts achieved by surgery.

For men, normal testosterone levels range from 300 to 1,000 ng/dl. The FDA requires that any new drug used in hormone therapy for prostate cancer lower testosterone levels to 50 ng/dl or less. In my practice, I usually try to lower levels even further, to 20 ng/dl.

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Therapies That Interfere With Androgen Function

Taken daily as pills, antiandrogens bind to the androgen receptor proteins in the prostate cells, preventing the androgens from functioning. In addition to preventing a flare reaction, antiandrogens may be added to your treatment plan if an orchiectomy, LHRH agonist or LHRH antagonist is no longer working by itself. Commonly prescribed antiandrogens include flutamide and bicalutamide .

Enzalutamide is a newer type of antiandrogen that blocks the signal that the receptor normally sends to the cells control center to trigger growth and division. This antiandrogen may be used to treat castration-resistant prostate cancer.

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What Is Advanced Prostate Cancer

Hormone Therapy for Prostate Cancer Treatment

When prostate cancer spreads beyond the prostate or returns after treatment, it is often called advanced prostate cancer.

Prostate cancer is often grouped into four stages, with stages III and IV being more advanced prostate cancer.

  • Early Stage | Stages I & II: The tumor has not spread beyond the prostate.
  • Locally Advanced | Stage III: Cancer has spread outside the prostate but only to nearby tissues.
  • Advanced | Stage IV: Cancer has spread outside the prostate to other parts such as the lymph nodes, bones, liver or lungs.

When an early stage prostate cancer is found, it may be treated or placed on surveillance . Advanced prostate cancer is not curable, but there are many ways to treat it. Treatment can help slow advanced prostate cancer progression.

There are several types of advanced prostate cancer, including:

Biochemical Recurrence

With biochemical recurrence, the prostate-specific antigen level has risen after treatment using surgery or radiation, with no other sign of cancer.

Castration-Resistant Prostate Cancer

Non-Metastatic Castration-Resistant Prostate Cancer

Prostate cancer that no longer responds to hormone treatment and is only found in the prostate. This is found by a rise in the PSA level, while the testosterone level stays low. Imaging tests do not show signs the cancer has spread.

Metastatic Prostate Cancer

  • Lymph nodes outside the pelvis
  • Bones
  • Other organs, such as liver or lungs

Metastatic Hormone-Sensitive Prostate Cancer

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What Kinds Of Medical Information Should I Keep

It is important for you to keep a copy of your prostate cancer treatment records. You may not always see the same doctor for your follow-up care, so having this information to share with another doctor can be very helpful. The following is a list of medical information you may want to keep.

  • The results of any tests you have taken such as your Prostate-Specific Antigen test.
  • When you found out you had prostate cancer.
  • Information on the kinds of treatment you have had for your prostate cancer including:
  • The places and dates where you had your treatment.
  • What type of treatment you had. And,
  • Any medicines you took before, during, and after your prostate cancer treatment.
  • Contact information for all your doctors and the other members of your health care team who helped with your prostate cancer treatment and followup care.
  • Any side effects or problems you had during and after your prostate cancer treatment.
  • Any supportive care you got during your treatment. Supportive care is treatment given to keep, control, or make your side effects better and to make your life better. For example, pain medicine, emotional support, and nutritional supplements.
  • What Side Effects May I Have After I Start Hormone Therapy

    The side effects that you may have after you start hormone therapy include: erectile dysfunction or impotence , lower sexual desire , hot flashes, fatigue , weight gain, breast enlargement, osteoporosis, anemia, memory loss, and cardiovascular problems. The following side effects can happen as soon as you start your treatment.

    Erection problems

    Difficulty getting or keeping an erection is a common side effect of hormone therapy for prostate cancer. This is also called impotence. Hormone therapy lowers the amount of testosterone in your body or stops your body from making testosterone.

    Lower sex drive

    Hot flashes and sweating

    Breast tenderness or growth

    Some men may find that their chest becomes sore and that their breasts get a little bit swollen. This is called gynecomastia . There are medicines and treatments that you doctor or health care team can give you to help with this side effect.

    Fatigue

    The drop in your testosterone level may make you feel very tired. You may feel tired all the time or you may get tired more easily when you do your daily activities. This is known as fatigue or tiredness. There are things you can do to help deal with this treatment side effect.

    Tumor flare pain

    The following side effects may happen if you take hormone treatment for a long period of time. These are:

    Weight gain

    There are several ways you can help to lower your osteoporosis risk

    Cardiovascular problems

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    What Types Of Hormone Therapy Are Used For Prostate Cancer

    Hormone therapy for prostate cancer can block the production or use of androgens . Currently available treatments can do so in several ways:

    • reducing androgen production by the testicles
    • blocking the action of androgens throughout the body
    • block androgen production throughout the body

    Treatments that reduce androgen production by the testicles are the most commonly used hormone therapies for prostate cancer and the first type of hormone therapy that most men with prostate cancer receive. This form of hormone therapy includes:

    Treatments that block the action of androgens in the body are typically used when ADT stops working. Such treatments include:

    Treatments that block the production of androgens throughout the body include:

    What Are The Side Effects Of Hormone Therapy For Prostate Cancer

    Hormone Therapy Basics | Ask a Prostate Cancer Expert, Mark Scholz, MD

    Because androgens affect many other organs besides the prostate, ADT can have a wide range of side effects , including:

    • loss of interest in sex
  • Studer UE, Whelan P, Albrecht W, et al. Immediate or deferred androgen deprivation for patients with prostate cancer not suitable for local treatment with curative intent: European Organisation for Research and Treatment of Cancer Trial 30891. Journal of Clinical Oncology 2006 24:18681876.

  • Zelefsky MJ, Eastham JA, Sartor AO. Castration-Resistant Prostate Cancer. In: Vincent T. DeVita J, Lawrence TS, Rosenberg SA, eds. DeVita, Hellman, and Rosenberg’s Cancer: Principles & Practice of Oncology, 9e. Philadelphia, PA: Lippincott Williams & Wilkins 2011.

  • Smith MR, Saad F, Chowdhury S, et al. Apalutamide and overall survival in prostate cancer. European Urology 2021 79:150158.

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    When You Have Bicalutamide

    Bicalutamide is a treatment for prostate cancer. You might have bicalutamide:

    • on its own
    • after an operation to remove your prostate
    • before you have other hormone treatments such as goserelin , leuprorelin and triptorelin

    Reducing tumour flare

    You need to take bicalutamide before you start some other types of hormone treatment because they take a few weeks to lower your testosterone. During this time they can make your symptoms worse. This is called tumour flare.

    If you are having bicalutamide to stop tumour flare, you take it for a few days before starting the luteinising hormone blocker, and stay on it for about 4 to 6 weeks.

    Bicalutamide is a tablet you take once a day.

    You should swallow the tablet whole with a glass of water.

    Table : Boosting The Effectiveness Of Radiation Therapy

    A randomized controlled study involving 206 men with early-stage prostate cancer evaluated whether adding six months of hormone therapy to external-beam radiation treatment would boost both overall survival and disease-free survival . The results are given below. The same research group found, in an earlier study, that the addition of hormone therapy was of most benefit to men who were considered at moderate or high risk, based on their clinical profile.

    Five-year follow-up 82% Source: Journal of the American Medical Association, 2004 292:8217. PMID: 15315996.

    Combined with radiation therapy. A number of studies have shown that men with early-stage prostate cancer are more likely to be cured when hormone therapy is given in conjunction with radiation therapy . Even when the disease is regionally advanced, meaning that it has progressed to tissues immediately surrounding the prostate gland, neoadjuvant hormone therapy reduces risk of progression and relapse .

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    Hormone Therapy Helps Some Prostate Cancer Survivors Live Longer

    A study published in the New England Journal of Medicine in January 2017 indicates that men whose prostates are removed to treat prostate cancer are likely to survive longer if they take drugs to block the male hormone testosterone in addition to undergoing radiation therapy.

    Unfortunately, its not that simple.

    What Kinds Of Medicines Can Be Used To Lower My Testosterone

    Why does hormone therapy worsen some prostate cancers?

    There are several types of medicines you can take to lower the amount of testosterone in your body. These are temporary ways to lower the amount of testosterone. When you stop taking these medicines, your testosterone level will begin to go up.

    LHRH agonist

    LHRH is a normal human hormone that tells your body to make testosterone. An LHRH agonist is a man-made hormone similar to the one made naturally in your body. LHRH agonists work like a light switch to shut off the production of testosterone in your body. When you are given this medicine, your body will stop making the LHRH hormone and your testicles will stop making testosterone. When you are first given this medicine, your body will continue to make testosterone for a couple of weeks. This means that your testosterone level may go up for a week or two and then begin to drop. This type of medicine works as well as having an orchiectomy . These medicines are given either monthly or every three months in a shot . The medicine may also be placed as small implants under your skin. The implant gives you a steady dose of medicine. Depending on the type of implant the medicine may last from one to 12 months.

    Anti-androgens

    Anti-androgens act like a brick wall. They block the small amount of testosterone made in your adrenal glands from reaching your prostate cancer cells. This keeps your prostate cancer cells from growing. These medicines are pills that are taken orally one to three times a day.

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    Hormone Therapy: Immediate Versus Delayed

    Medical Research Council Prostate Cancer Working Party Investigators Group. Immediate Versus Deferred Treatment for Advanced Prostatic Cancer. British Journal of Urology 1997 79:23546. PMID: 9052476.

    Messing EM, Manola J, Sarosdy M, et al. Immediate Hormonal Therapy Compared with Observation after Radical Prostatectomy and Pelvic Lymphadenectomy in Men with Node-Positive Prostate Cancer. New England Journal of Medicine 1999 341:17818. PMID: 10588962.

    Messing EM, Manola J, Yao J, et al. Immediate Versus Deferred Androgen Deprivation Treatment in Patients with Node-Positive Prostate Cancer after Radical Prostatectomy and Pelvic Lymphadenectomy. Lancet Oncology 2006 7:4729. PMID: 16750497.

    Nair B, Wilt T, MacDonald R, Rutks I. Early Versus Deferred Androgen Suppression in the Treatment of Advanced Prostatic Cancer. Cochrane Database of Systematic Reviews 2002 CD003506. PMID: 11869665.

    How Will I Know That My Hormone Therapy Is Working

    Doctors cannot predict how long hormone therapy will be effective in suppressing the growth of any individual mans prostate cancer. Therefore, men who take hormone therapy for more than a few months are regularly tested to determine the level of PSA in their blood. An increase in PSA level may indicate that a mans cancer has started growing again. A PSA level that continues to increase while hormone therapy is successfully keeping androgen levels extremely low is an indicator that a mans prostate cancer has become resistant to the hormone therapy that is currently being used.

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    Systemic Therapy For Metastatic Disease

    The most common use of hormone therapy today is to treat men whose prostate cancer has metastasized to other parts of the body. If prostate cancer cells escape the prostate, they migrate first to surrounding structures, such as the seminal vesicles and lymph nodes, and later to the bones or, rarely, to other soft tissues.

    Hormone therapy is recommended as a palliative treatment, to relieve symptoms such as bone pain. And while hormone therapy is not a cure, in that it cant eliminate prostate cancer completely, it often extends life for many years. By reducing testosterone levels, hormone therapy can shrink a prostate tumor and its metastases and slow further progression of the cancer for so long that sometimes a man with this disease dies of something other than prostate cancer.

    Evidence About Hormone Therapy And Prostatectomy

    Intermittent Hormone Therapy: PSA and Hormone Replacement | Ask a Prostate Expert, Mark Scholz, MD

    Gleave ME, La Bianca S, Goldenberg SL. Neoadjuvant Hormonal Therapy Prior to Radical Prostatectomy: Promises and Pitfalls. Prostate Cancer and Prostatic Diseases 2000 3:13644. PMID: 12497089.

    Hurtado-Coll A, Goldenberg SL, Klotz L, Gleave ME. Preoperative Neoadjuvant Androgen Withdrawal Therapy in Prostate Cancer: The Canadian Experience. Urology 2002 60:4551. PMID: 12231047.

    Kumar S, Shelley M, Harrison C, et al. Neo-adjuvant and Adjuvant Hormone Therapy for Localized and Locally Advanced Prostate Cancer. Cochrane Database of Systematic Reviews 2006 CD006019. PMID: 17054269.

    Soloway MS, Sharifi R, Wajsman Z, et al. Randomized Prospective Study Comparing Radical Prostatectomy Alone Versus Radical Prostatectomy Preceded by Androgen Blockade in Clinical Stage B2 Prostate Cancer. The Lupron Depot Neoadjuvant Prostate Cancer Study. Journal of Urology 1995 154:4248. PMID: 7541859.

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    How Might Hormone Therapy Make Me Feel

    Hormone therapy itself can affect your mood. You may find that you feel more emotional than usual or just different to how you felt before. Some men find that they cry a lot. You may also get mood swings, such as getting tearful and then angry. Just knowing that these feelings are caused by hormone therapy can help.

    Everyones different some men are surprised by the side effects and how upsetting they find them. Others have fewer symptoms or are not as worried by them.

    Some of the other side effects of hormone therapy are hard to come to terms with. Physical changes, such as putting on weight, or changes to your sex life, might make you feel very different about yourself. Some men say they feel less masculine because of their diagnosis and treatment.

    If youre starting hormone therapy very soon after being diagnosed with prostate cancer, you might still feel upset, shocked, frightened or angry about having cancer. These feelings are normal, and it’s okay to feel this way.

    Things in your day-to-day life can change because of the hormone therapy. Your relationships with your partner, family and friends might change. Or you might be too tired to do some of the things you used to do.

    Some men experience low moods, anxiety or depression. This could be directly caused by the hormone therapy itself, or because you’ve been diagnosed with prostate cancer. It could also be due to the impact that treatment is having on you and your family.

    What can help?

    Talking about it

    Cancer That Clearly Has Spread

    If the cancer has spread outside the prostate, it will most likely go to nearby lymph nodes first, and then to bones. Much less often the cancer will spread to the liver or other organs.

    When prostate cancer has spread to other parts of the body , hormone therapy is probably the most effective treatment. But it isnt likely to cure the cancer, and at some point it might stop working. Usually the first treatment is a luteinizing hormone-releasing hormone agonist, LHRH antagonist, or orchiectomy, sometimes along with an anti-androgen drug or abiraterone. Another option might be to get chemotherapy along with the hormone therapy. Other treatments aimed at bone metastases might be used as well.

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    Surgically Removing The Prostate Gland

    A radical prostatectomy is the surgical removal of your prostate gland. This treatment is an option for curing prostate cancer that has not spread beyond the prostate or has not spread very far.

    Like any operation, this surgery carries some risks, such as urinary incontinence and erectile dysfunction.

    In extremely rare cases, problems arising after surgery can be fatal.

    It’s possible that prostate cancer can come back again after treatment. Your doctor should be able to explain the risk of your cancer coming back after treatment, based on things like your PSA level and the stage of your cancer.

    Studies have shown that radiotherapy after prostate removal surgery may increase the chances of a cure, although research is still being carried out into when it should be used after surgery.

    After a radical prostatectomy, you’ll no longer ejaculate during sex. This means you will not be able to have a child through sexual intercourse.

    You may want to ask your doctors about storing a sperm sample before the operation so it can be used later for in vitro fertilisation .

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