How Long Does Hormone Therapy Work To Stop Cancer Progression
On average, hormone therapy can stop cancer progression for 1-2 years before the prostate cancer becomes resistant. Hormone therapy can stop working over time as the prostate cancer begins to grow again .
When this occurs, doctors may offer other therapies. Since they cant predict how long hormone therapy will work, they may perform regular blood tests to check PSA and testosterone levels. If PSA levels start to increase and testosterone levels are low, these may be signs that the cancer has started to grow again.
Who Is The Ideal Patient For Immunotherapy
Patients with prostate cancer who do not respond to other treatments, including radiation or surgery, may be candidates for immunotherapy. This therapy works by triggering the bodys immune system to destroy cancer cells. It has also been shown to be effective in a small number of patients with advanced, metastatic disease. While immunotherapy has several potential benefits, it has some limitations.
Prostate cancer has a unique immunological profile that makes it an ideal candidate for immunotherapy. Unlike other cancers, prostate tumours are relatively slow-growing and have less genetic variation. This means that they are not as easily targeted by T cells. But this does not mean that immunotherapy is not effective in all stages of the disease.
A recent study has found that immunotherapy may be more effective in patients with advanced prostate cancer. Researchers found that anti-CTLA-4 antibodies can recruit T cells to tumors, a process known as tumor-infiltrating lymphatic system. Moreover, these drugs are not only effective in metastatic disease but also may prolong life.
Drugs That Stop Androgens From Working
For most prostate cancer cells to grow, androgens have to attach to a protein in the prostate cancer cell called an androgen receptor. Anti-androgens are drugs that also connect to these receptors, keeping the androgens from causing tumor growth. Anti-androgens are also sometimes called androgen receptor antagonists.
Drugs of this type include:
They are taken daily as pills.
In the United States, anti-androgens are not often used by themselves:
- An anti-androgen may be added to treatment if orchiectomy or an LHRH agonist or antagonist is no longer working by itself.
- An anti-androgen is also sometimes given for a few weeks when an LHRH agonist is first started. This can help prevent a tumor flare.
- An anti-androgen can also be combined with orchiectomy or an LHRH agonist as first-line hormone therapy. This is called combined androgen blockade . There is still some debate as to whether CAB is more effective in this setting than using orchiectomy or an LHRH agonist alone. If there is a benefit, it appears to be small.
- In some men, if an anti-androgen is no longer working, simply stopping the anti-androgen can cause the cancer to stop growing for a short time. This is called the anti-androgen withdrawal effect, although it is not clear why it happens.
Enzalutamide , apalutamide and darolutamide are newer types of anti-androgens. They can sometimes be helpful even when older anti-androgens are not.
These drugs are taken as pills each day.
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What Should I Tell My Doctor During My Checkups
During each visit, you should tell your doctor about any:
- Symptoms that you have
- Pain that bothers you
- Problems that keep you from doing your daily activities, such as fatigue , hot flashes, pain, problems with your bladder, bowel, or ability to have sex, trouble sleeping, and weight gain or loss
- Medicines, vitamins, or herbs or over-the-counter products you are taking and any other treatments you may use
- Emotional worries you may have, such as anxiety or depression
It is important for you to look out for changes in your health and to tell your doctor or health care team so that they can help you.
Planning Before You Start Hormone Therapy
- What type of hormone therapy will you use?
- If you are taking medicine for your hormone therapy, what kind of medicine are you taking and how often do you need to take it? Write down the medicine, the dose, and when you need to take it.
- If you are having an orchiectomy where do you need to go, when will you have your surgery? Write down the place and your appointment time.
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The Side Effects Of Anti
Most men tolerate anti-androgen therapy well.
- Bone density loss
- Irritability or mood swings
- Enlargement of breasts
- Starting patients on Vitamin D and calcium, providing consultation with our endocrinology team about preserving bone health, and getting baseline bone density scans when indicated
- Encouraging men to commit to active physical therapy and aerobic exercise to limit weight gain, preserve muscle composition, and even retain urinary function and control it better
- Recommending medications to help with hot flashes and mood changes that can arise during hormone therapy
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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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.
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Hormone Therapy And Prostate Cancer
Prostate cancer is fueled by testosterone, a hormone produced in the testicles. The aim of HT is to interfere with either testosterone production or cancer cells’ ability to use testosterone. Medical evidence tells us that eliminating or substantially reducing testosterone production has a significant impact on controlling progression of the disease and may even halt progression. Testosterone is one of several hormones called androgens that are linked to sexual health and other processes in the body. This is why HT is often referred to as androgen deprivation therapy .
To be clear, this is not the “hormone therapy” of which you often hear. Women get “hormone therapy” to supplement waning estrogen levels, and older men without prostate cancer may get “hormone therapy” that administers additional testosterone. The “hormone therapy” we are talking about for men with prostate cancer is more accurately described as androgyn deprivation therapy . It is given to lower testosterone levels.
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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.
When Is Hormone Therapy Used For Prostate Cancer
On its own, hormone therapy can be a good way to control the growth of your prostate cancer. It can also be used with another prostate cancer treatment to help it work better. You should keep in mind that the following things will affect when you have hormone therapy and if you have hormone therapy along with another type of prostate cancer treatment:
- The grade of your prostate cancer
- Your Gleason score
- The stage of your prostate cancer
- Your general health
Your stage, grade, and Gleason score are determined by a pathologist. A pathologist is a specially trained physician who reviews biopsy results in order to find changes in your body caused by cancer. When you had your prostate biopsy, the pathologist looked at the tissue samples taken from your prostate gland and prepared your biopsy report. The report tells you and your doctor the following information:
- The grade tells you what your prostate cancer cells look like.
- The Gleason score. The Gleason score tells you what your prostate cancer cells look like compared to healthy cells and gives you an idea of how quickly your cancer is growing. Your Gleason score will range from 2 to 10.
- The stage tells how much prostate cancer you have and where your cancer is located.
This information is used to help your doctor chose the most effective type of hormone therapy for you. The types of hormone therapy include:
Neoadjuvant hormone therapy
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Hormone Therapy With Radiation
Hormone therapy is often given together with radiation therapy for localized disease .
Hormone therapy usually consists of a shot that lowers your testosterone, given every 1 to 6 months, depending on the formulation. Sometimes, it is prescribed as a daily pill that blocks testosterone from reaching the cancer cells. Clinical trials show a benefit in patients who receive hormonal treatment in combination with external beam radiation. Hormone therapy has been shown to improve cure rates of prostate cancer for men receiving radiation therapy and is part of the standard of care for men with certain types of intermediate-risk prostate cancer and nearly all high-risk prostate cancer. It is often given for intermediate-risk cancer for 4 to 6 months , and for 2 to 3 years in men with high-risk localized prostate cancer, although some doctors may recommend as little as 18 months of hormone therapy.
Hormone therapy should not be given to men with low-risk prostate cancer and is not a standalone treatment for localized prostate cancer in any risk category.
Want more information about a prostate cancer diagnosis and treatment options? Download or order a print copy of the Prostate Cancer Patient Guide.
Forms Of Hormonal Manipulation And Hormonal Suppression
Hormone therapy, also described as ADT or androgen suppression therapy , allows for a decrease in serum testosterone in an effort to slow down the growth of CaP. Multiple medications and strategies have been used to induce castrate serum levels of testosterone or to interfere with its function. One of earliest methods described in the 1940s by Huggins and Hodges was bilateral orchiectomy . Surgical castration results in an effective reduction of circulating testosterone within a few hours, and still remains an underutilized method in the treatment of advanced CaP.
Several nonsurgical options exist in achieving hormonal suppression. Diethylstilbestrol , a semisynthetic estrogen compound, was one of the first nonsurgical options for the treatment of CaP. At one time a first-line hormonal therapy, its widespread use has been limited due to significant cardiovascular and thromboembolic toxicity. Cyproterone acetate is a steroidal, progestational antiandrogen that blocks the androgen-receptor interaction and reduces serum testosterone through a weak antigonadotropic action. CPA is also associated with a high rate of cardiovascular complications, and is not available in the United States.
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Combined Androgen Blockade: Pro And Con
Crawford ED, Eisenberger MA, McLeod DG, et al. A Controlled Trial of Leuprolide With and Without Flutamide in Prostatic Carcinoma. New England Journal of Medicine 1989 321:41924. PMID: 2503724.
Eisenberger MA, Blumenstein BA, Crawford ED, et al. Bilateral Orchiectomy With or Without Flutamide for Metastatic Prostate Cancer. New England Journal of Medicine 1998 339:103642. PMID: 9761805.
Two large meta-analyses that reviewed many studies comparing combined androgen blockade to monotherapy concluded that the combination offered only a small survival advantage and even that finding was inconsistent between the two analyses. One analysis, which reviewed 27 randomized studies involving 8,275 men, estimated that combined androgen blockade improved five-year survival by only 2% to 3%, at most. However, an advantage of only 2% to 3%, when applied to thousands of men undergoing treatment, translates into hundreds of lives extended obviously an important benefit to the men who gain months and even years of life as a result. That is why I use combined therapy for all of my patients who undergo hormone treatments.
Table : Survival Benefits Of Early Treatment
An analysis of 98 men with prostate cancer that had spread to the lymph nodes, who were randomly assigned to receive immediate hormone therapy or to forgo it until the disease spread further to bones or lungs, found that early treatment saved lives.
Deaths from prostate cancer 21 Source: Lancet Oncology 2006 7:4729. PMID: 16750497.
Other studies have shown that starting hormone therapy early on increases survival times, delays cancer progression, and results in better quality of life. However, in a review of four studies involving 2,167 men with metastatic prostate cancer, the Cochrane Collaboration concluded that early hormone therapy had offered only a small overall survival advantage over deferred treatment, and cautioned that more research on the issue needs to be done.
Although debate on this issue continues, in most cases I advise my patients with metastatic disease to begin hormone treatment early on. This is particularly important for someone with spine metastases, because a bone fracture or extension of the cancer into the spinal cord area could lead to impaired mobility and even paralysis. Fortunately, this is a rare event.
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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.
What Are Estrogen And Progesterone Receptors
Normal breast cells and some breast cancer cells contain receptors that attach to estrogen and progesterone. These 2 hormones often fuel the growth of breast cancer cells. An important step in evaluating a breast cancer is to test the cancer removed during the biopsy to see if it has estrogen and progesterone receptors.
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Another type of prostate issue is chronic prostatitis, or chronic pelvic pain syndrome. This condition causes pain in the lower back and groin area, and may cause urinary retention. Symptoms include leaking and discomfort. In severe cases, a catheter may be required to relieve the symptoms. If the problem is unresponsive to other treatments, your doctor may suggest a surgical procedure. If these do not work, your symptoms could progress and become chronic.
An acute bacterial infection can cause a burning sensation. Inflammation of the prostate can affect the bladder and result in discomfort and other symptoms. This is the most common urinary tract problem in men under 50, and the third most common in men over 65. The symptoms of acute bacterial prostatitis are similar to those of CPPS. Patients may experience a fever or chills as a result of the infection.
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Mechanisms Of Androgen Receptor Signaling
Figure 2 The structure of the androgen receptor gene and protein. The AR gene is situated on position q11-12 of chromosome X and contains 8 exons. The protein reference sequence NM_000044.3 is comprised of 920 amino acids and is composed of different domains which are depicted. In addition, posttranslational modifications known to influence AR function are shown. AR, androgen receptor bp, base pair NTD, N-terminal domain DBD, DNA binding domain LBD, ligand binding domain AF, activation function TAU, transcription activation unit NLS, nuclear localisation signal NES, nuclear export signal.
Figure 3 Genomic androgen receptor signaling pathway. Androgens, such as testosterone and dihydrotestosterone, enter the cell and are converted in the more active metabolite by the steroid-5-reductase. Upon ligand binding heat stress protein chaperones are released and AR undergoes conformational change and dimerization. In the nucleus the AR together with co-regulators activates the transcription of androgen regulated genes. T, testosterone AR, androgen receptor DHT, 5-dihydrotestosterone HSP, heat shock TF, transcription factor ARE, Androgen Response Element.
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What Type Of Hormone Therapy Works Best
Unfortunately, understanding the details of hormone therapy for prostate cancer can be difficult. Which drug or combination of drugs works best? In what order should they be tried? Research hasn’t answered these questions yet.
“Right now, there’s a level of art to figuring out which agents to use,” says Durado Brooks, MD, MPH, director of prostate cancer programs at the American Cancer Society. “We don’t have clear evidence yet.”
LHRH agonists remain the usual first treatment. But in some cases, doctors are trying anti-androgens first. Anti-androgens may be especially appealing to younger men who are still sexually active, since these drugs don’t completely shut down sex drive. When anti-androgens stop working — based on PSA tests — a person then might shift onto an LHRH agonist.
Other doctors prefer to begin therapy with a combination of two or even three drugs, especially for patients with symptoms or advanced disease, says Holden.
Researchers originally hoped that combined androgen blockade would significantly add to the benefits of LHRH agonists. However, the results, to date, have been mixed. Some studies have shown slightly longer survival with combined androgen blockade, but the results haven’t been as dramatic as many experts had hoped. Other studies have shown no benefit. A possible explanation may be the type of anti-androgen used, but further studies are needed to answer this question.