Hormone (Androgen Deprivation) Therapy

Hormone therapy is also called androgen deprivation therapy (ADT) or androgen suppression therapy. The goal is to reduce levels of the male hormones, called androgens, in the body. The main androgens are testosterone and dihydrotestosterone (DHT). Androgens, produced mainly in the testicles, stimulate prostate cancer cells to grow. Lowering androgen levels often makes prostate cancers shrink or grow more slowly. However, hormone therapy does not cure prostate cancer.


Hormone therapy may be used in several situations:

* If you are not able to have surgery or radiation or can't be cured by these treatments because the cancer has already spread beyond the prostate gland
* If your cancer remains or comes back after treatment with surgery or radiation therapy
* As an addition to radiation therapy as initial treatment if you are at high risk for cancer recurrence
* Before surgery or radiation to try and shrink the cancer to make other treatments more effective

Types of Hormone Therapy

There are several types of hormone therapy used to treat prostate cancer.

Orchiectomy (surgical castration): Even though this is a type of surgery, its main effect is as a form of hormone therapy. In this operation, the surgeon removes the testicles, where more than 90% of the androgens, mostly testosterone, are made. With this source removed, most prostate cancers stop growing or shrink for a time.

This is done as a simple outpatient procedure. It is probably the least expensive and simplest way to reduce androgen levels in the body. But unlike some of the other methods of lowering androgen levels, it is permanent, and many men have trouble accepting the removal of their testicles. Some men having the procedure are concerned about how it will look. If wanted, artificial silicone sacs filled with saline (salt water) can be inserted into the scrotum. These look and feel like testicles.

Possible side effects of orchiectomy are generally related to changing levels of hormones in the body. About 90% of men who have had this operation have reduced or absent libido (sexual desire) and impotence. Some men also experience:

* Hot flashes (these may go away with time)
* Breast tenderness and growth of breast tissue
* Osteoporosis (bone thinning) which can lead to broken bones
* Anemia (low red blood cell counts)
* Decreased mental acuity (sharpness)
* Loss of muscle mass
* Weight gain
* Fatigue
* Decrease in HDL ("good") cholesterol
* Depression

Many of these side effects can be prevented or treated. For example, sometimes the hot flashes will be helped by treatment with antidepressants. Brief radiation treatment to the breasts before surgery can help prevent their enlargement.

Men getting this treatment should be watched and treated for osteoporosis to help prevent broken bones. There are several different drugs available. Exercise is a good way to reduce fatigue, weight gain, and the chance of loss of bone and muscle mass. If anemia occurs, it is often very mild and usually doesn't cause symptoms. Depression can be treated by antidepressants and/or counseling.

Luteinizing hormone-releasing hormone (LHRH) analogs: Even though LHRH analogs (also called LHRH agonists) cost more and require more frequent doctor visits, most men choose this method over orchiectomy. These drugs lower testosterone levels just as well as orchiectomy by lowering the levels of androgens (mainly testosterone) made by your testicles.

LHRH analogs are injected or placed as small implants under the skin. They are given either monthly or every 3, 4, 6, or 12 months. The LHRH analogs available in the United States include leuprolide (Lupron, Viadur, Eligard), goserelin (Zoladex), and triptorelin (Trelstar).

Possible side effects of LHRH analogs such as hot flashes, osteoporosis, and others are similar to those of orchiectomy (see above), and are largely due to low testosterone levels.

When LHRH analogs are first given, testosterone production increases briefly before falling to very low levels. This effect is called flare and results from the complex way in which LHRH analogs work. Men whose cancer has spread to the bones may experience bone pain. If the cancer has spread to the spine, even a short-term increase in growth could compress the spinal cord and cause pain or paralysis. Flare can be avoided by giving drugs called anti-androgens for a few weeks when starting treatment with LHRH analogs. (For more on anti-androgens, see below.)

Luteinizing hormone-releasing hormone (LHRH) antagonists: A newer drug, abarelix (Plenaxis), is an LHRH antagonist. It is thought to work like LHRH agonists, but it appears to reduce testosterone levels more quickly and does not cause tumor flare like the LHRH agonists do.

A small percentage of men (fewer than 5%) have serious allergic reactions to the drug. Because of this, it is only approved for use in men who have serious symptoms from advanced prostate cancer and who cannot or refuse to take other forms of hormone therapy.

The possible side effects are similar to those with orchiectomy (see above) or LHRH agonists.

Abarelix is given only in qualified doctors' offices. It is injected into the buttocks every 2 weeks for the first month, then every 4 weeks. You will be asked to remain in the office for 30 minutes after the injection to make sure you are not having an allergic reaction.

Anti-androgens: Anti-androgens block the body's ability to use any androgens. Even after orchiectomy or during treatment with LHRH analogs, a small amount of androgens is still made by the adrenal glands.

Drugs of this type, such as flutamide (Eulexin), bicalutamide (Casodex), and nilutamide (Nilandron), are taken daily as pills.

Anti-androgens are not often used by themselves (see below). An anti-androgen may be added if treatment with orchiectomy or an LHRH analog is no longer working by itself.

Anti-androgen treatment may be combined with orchiectomy or LHRH analogs as first-line hormone therapy. This is called combined androgen blockade (CAB). There is still some debate as to whether CAB is more effective in this setting than using orchiectomy or an LHRH analog alone. If there is a benefit, it appears to be small.

Some doctors are testing the use of anti-androgens instead of orchiectomy or LHRH analogs. Several recent studies have compared the effectiveness of anti-androgens alone with that of LHRH agonists. Most found no difference in survival rates, but a few found anti-androgens to be slightly less effective.

If hormone therapy including an anti-androgen stops working, some men seem to benefit for a short time from simply stopping the anti-androgen. Doctors call this the "anti-androgen withdrawal" effect, although they are not sure why it happens.

Side effects of anti-androgens in patients already being treated by orchiectomy or with LHRH agonists are usually not serious. Diarrhea is the major side effect, although nausea, liver problems, and tiredness can also occur.

The major difference from LHRH agonists and orchiectomy is that anti-androgens may have fewer sexual side effects. When these drugs are used alone libido and potency can often be maintained.

Other androgen-suppressing drugs: Estrogens were once the main alternative to orchiectomy for men with advanced prostate cancer. Because of their possible side effects (including blood clots and breast enlargement), estrogens have been largely replaced by LHRH analogs and anti-androgens. Still, estrogens may be tried if androgen deprivation is no longer working.

Ketoconazole (Nizoral), first used for treating fungal infections, blocks production of androgens and is sometimes used.


Current Controversies in Hormone Therapy

There are many issues around hormone therapy that not all doctors agree on, such as the best time to start and stop it and the best way to give it. Studies looking at these issues are now under way. A few of the issues are discussed here.

Early vs. delayed treatment: Some doctors think that hormone therapy works better if it is started as soon as possible if the cancer has reached an advanced stage (for example, when it has spread to lymph nodes), if it is large (T3) or has a high Gleason score, or if the PSA starts rising after initial therapy, even though the patient feels well. Some studies have shown that hormone treatment may slow down the disease and perhaps even lengthen patient survival. But not all doctors agree with this approach. Some are waiting for more evidence of benefit. They feel that because of the likely side effects and the chance that the cancer could become resistant to therapy sooner, treatment should not be started until symptoms from the disease appear. Studies addressing these questions are now under way.

Intermittent vs. continuous hormone therapy: Nearly all prostate cancers treated with hormone therapy become resistant to this treatment over a period of months or years. Some doctors believe that constant androgen suppression may not be needed, so they advise intermittent (on-again, off-again) treatment.

In one form of intermittent therapy, androgen suppression is stopped once the blood PSA level drops to a very low level. If the PSA level begins to rise, the drugs are started again. Another form of intermittent therapy involves using androgen suppression for fixed periods of time -- for example, 6 months on followed by 6 months off.

Clinical trials of intermittent hormonal therapy are still in progress. It is too early to say whether this new approach is better or worse than continuous hormonal therapy. However, one advantage of intermittent treatment is that for a while some men are able to avoid the side effects of hormonal therapy such as impotence, hot flashes, and loss of sex drive.

Combined androgen blockade (CAB): Some doctors treat patients with both androgen deprivation (orchiectomy or an LHRH agonist) and an anti-androgen. But most doctors are not convinced there's enough evidence that this combined therapy is better than one drug alone.

Triple androgen blockade (TAB): Some doctors have suggested taking combined therapy one step further, by adding a drug called a 5-alpha reductase inhibitor -- either finasteride (Proscar, Propecia) or dutasteride (Avodart) -- to the combined androgen blockade. There is very little evidence to support the use of this "triple androgen blockade" at this time.

Last Revised: 08/25/2008

My PSA Reading

Updated: Now includes a video presentation on PSA Readings. Click on the video link below; also visit the host site for more educational videos.

On Friday 30th November, I attended our local GP's surgery for another blood test. Specifically, this blood test was to:

• Determine whether my PSA reading [previously 84.8] had begun to drop. Thus showing that the hormonal therapy I had been undergoing for a little over 4 weeks, had in fact begun to have the desired affect; and
  
  
• Determine whether my cholesterol readings had improved as a result of my [now] 'extremely healthy' diet.

I was told that it is quite normal for the PSA to rise after a trans-rectal biopsy. I was also told to bear in mind, that I had only begun the hormone therapy 4 weeks prior to the blood test. [Orally for the first two weeks (i.e. Androcur - anti-agonist), followed by an LHRH implant and continuing the oral regime until two weeks after the implant procedure].

Well ... the results are in! And, as often happens, there is good news and bad news. The bad news relates to the fact that one of my readings had not altered at all!

My 'cholesterol level' has refused to budge!!

The good news ... well my PSA levels have gone down - very significantly! My previous PSA was 84.8. It is now 12 [only one month after receiving the LHRH implant]!!

For more on the significance of a PSA test I invite you to watch the following video, 'Prostate Cancer Predictors - PSA Test'. Other educational videos in the series are available at: Sutter Health.

Prostate Cancer - A Glossary

Updated: Now includes an extensive 'online' glossary and also an online acronym and abbreviations decipher.

Researching Prostate Cancer, as a lay person, proved to be rather difficult at first. I really had no point of reference or basis for understanding (or remembering) either the medical terms or the anatomical names!

So, my solution, was to find a glossary of terms that would assist me on my endeavour until such times that the terms etc, became familiar to me by virtue of common usage. It is with this in mind, I offer the following as an aid to other lay persons who find themselves on the same journey.

Ablation - Removal or separation of something.

Adrenal glands - Small glands lying on top of the kidneys which produce a small amount of male hormone.

Androgens - Male hormones. The most active male hormone, testosterone, is produced by the testicles. Other male hormones are produced by the adrenal glands.

Anti-androgens - Drugs which block the effects of male hormones.

Asymptomatic - Not having symptoms, symptom-free.

Benign - Non-cancerous (not cancer).

Benign prostate enlargement - Non-cancerous enlargement of the prostate.

BPH - Benign Prostatic Hyperplasia. A condition causing non-cancerous enlargement of the prostate.

Biopsy of the prostate - Removal of small pieces of tissue, in this case, from the prostate gland. Tissue samples are taken from different areas of the prostate, and then examined under the microscope to see if they are cancerous.

Brachytherapy - A type of prostate radiotherapy - involves the insertion of radioactive seeds or rods directly into the prostate.

CAT (CT) scan - CAT stands for Computerised Axial Tomography. A series of x-ray pictures are taken in a circle around the body and are processed by a computer.

Chemotherapy - Usually refers to the killing of cancer cells with cytotoxic chemicals (cytotoxic means toxic to cells.)

Cystitis - Inflammation of the bladder, often caused by infection.

Cystoscope - A tiny tube with a lighted end which slides along the urethra and is used to examine the bladder.

Digital Rectal Examination (DRE) - An examination of the prostate through the rectum wall. The doctor inserts a finger in the rectum and feels the shape of the prostate. Irregularities may be caused by cancer.

Dry ejaculation - Also called reverse or retrograde ejaculation. After surgery on the prostate, a man may achieve orgasm, but produce no ejaculate. This is because of either the removal of a muscular valve which prevents the ejaculate from going backwards into the bladder (in the case of surgery called a TURP), or because the glands which produce much of the fluid in the ejaculate are also removed (in the case of a radical prostatectomy).

Ejaculate - Fluid produced at ejaculation which contains sperm and secretions from glands such as the prostate, seminal vesicles and testicles.

Gleason score - A way of grading cancer cells. Low grade cancers (Gleason score 2,3,4) are slower growing than high grade (Gleason scores 8,9,10) cancers.

Grade - A way of describing how abnormal the cancer cells look, and consequently how aggressive or fast-growing the cancer is likely to be. The most commonly used grading system is the Gleason score, which ranges from 2-10.

Hot flush - A sudden rush of heat to the face, neck, sometimes chest and back. It can be associated with hormonal therapy for prostate cancer.

Hormone resistance - Prostate cancer cells are dependent on testosterone or male hormone for growth. Withdrawal of male hormone by surgery or by means of drugs is therefore a means of controlling its growth. However cancer cells may develop which do not need testosterone for growth. The cancer is then said to be ‘hormone resistant’.

Hyperthermia - Higher than normal temperature. In the case of prostate cancer, a way of destroying tissue by heating.

Impotence - Inability to achieve an erection.

Indolent - Means ‘lazy’, usually referring to the type of cancer cells which grow only slowly.

Incontinence - Inability to hold urine or control urine loss.

Lymph nodes - Small glands which filter tissue fluid before it returns to the blood stream. This means that they often capture cancer cells which have escaped from the main tumour and have started to spread to other parts of the body.

LHRH - Luteinising Hormone Releasing Hormone. It is produced by the hypothalamus in the brain and stimulates the pituitary (another part of the brain) to produce LH (Luteinising Hormone). This, in turn causes cells in the testicles to produce testosterone, the male hormone.

LHRH agonists - Drugs which interfere with the production of LH (see above) by the pituitary.

Libido - Sex drive.

Margin-positive - See surgical margins.

Metastasis - A piece of cancer which has broken off from the main cancer and become established in a different part of the body. Prostate cancer metastases often occur in lymph glands, bone or in the lungs.

MRI - Magnetic Resonance Imaging. A way of imaging the inside of the body without using X-rays.

Nodules - Small lumps.

Oncologist - A doctor who specialises in treating cancer.

Orchidectomy - (Also Orchiectomy) A type of operation which removes the testicles, but usually leaves the scrotal sac or scrotum.

Pelvis/pelvic - The area of the body below the waist and surrounded by the hip and pubic bones.

Pituitary - Part of the brain which produces hormones which stimulate the testicles to produce testosterone (male hormone) and other hormones.

Prostatitis - Inflammation of the prostate. It can be caused by bacteria.

Prostatectomy - Operation to remove all or part of the prostate.

PSA - Prostate Specific Antigen. It can be used as a test for prostate cancer or to monitor its recurrence.

Radical prostatectomy - An operation which removes the prostate and the seminal vesicles. This may be done through a cut in the abdomen or the perineum (the area of skin between the rectum & scrotum).

Rectum - The last part of the bowel, leading to the anus, and through which stool passes.

Retrograde - Also called reverse ejaculation. This may occur after surgery for benign enlargement of the prostate. The ejaculate travels back into the bladder instead of exiting out through the penis. This means a man is infertile, but he can still achieve orgasm.

Scrotum - A pouch of skin which contains the testicles and some other parts of the male repro-ductive system. It hangs outside the body and below the penis.

Seminal vesicles - Glands which lie very close to the prostate and produce secretions which form part of the ejaculate.

Staging - A way of describing how far the cancer has spread.

Stricture - Scar tissue which obstructs fluid flow; in the case of a urethral stricture, urine flow is obstructed.

Surgical margins - After a radical prostatectomy, the edges of the tissue which has been removed are examined to see if cancer cells are present. If they are not (negative surgical margins) the chance is higher that all of the cancer has been removed.

Testicles - Glands which produce sperm and the male hormone, testosterone. They are found in the scrotum.

Testosterone - The major male hormone. It is produced by the testicles.

TRUS - Trans-Rectal Ultra-Sound. A means of imaging the prostate in order to locate cancer. The ultrasound probe is placed in the rectum.

TURP - Trans-Urethral Resection of the Prostate. An instrument is inserted, under anaesthetic, along the urethra (urine tube) and removes prostate tissue which may be blocking the flow of urine. It is a common operation for benign enlargement of the prostate, but only occasionally used to treat prostate cancer.

Urethra - Tube which carries urine and ejaculate along the length of the penis and to the outside.

Online Glossary: Acronyms and Abbreviations: Courtesy of: Prostate Cancer research Institute

Staging Prostate Cancer

Updated to include a video of an MRI scan. Click on 'MRI' link in Regional Lymph Nodes (N).

The following article is excerpted from PSA Rising - Prostate Cancer Survivor (News, Info & Support) in the hope readers may become more informed. I would encourage all our readers to visit the author's website.


What is Staging?

If prostate cancer has been found by any method, the next step is to see how much of the prostate it takes up and whether it has spread outside the prostate to nearby tissue, lymph nodes, organs and/or bones.

This is called staging the cancer. Your prostate cancer stage is key to your treatment options. Primarily, staging is based on your digital rectal exam (DRE).


Two different systems of staging have been used for prostate cancer.

Today the older ABCD system has largely been replaced by the TNM (Tumor, Nodes, Metastases) system. In addition, two levels of staging are used, clinical and pathologic.

Clinical staging is based on digital exam and any further non-invasive tests necessary to find the extent of the cancer. It affects primary treatment decisions.

Pathologic stage refers to examination of the prostate and any other tissue removed during surgery. Only patients who undergo surgery receive the second level of staging.


The TNM system of staging

Primary tumor (T)

TX: Tumor cannot be assessed.

T1: Doctor is unable to feel the tumor or see it with imaging such as transrectal ultrasound.

T1a: Cancer is found incidentally during a transurethral resection (TURP) for benign prostatic enlargement. Cancer is present in less than 5% of the tissue removed.

T1b: Cancer is found after TURP and is present in more than 5% of the tissue removed.

T1c: Cancer is found by needle biopsy done because of an elevated PSA.

T2: Doctor can feel the tumor when a digital rectal exam (DRE) is performed but the tumor still appears to be confined to the prostate.

T2a: Cancer is found in one half or less of only one side (left or right) of the prostate.

T2b: Cancer is found in more than half of only one side (left or right) of the prostate.

T2c: Cancer is 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 tissues next to the prostate (other than the seminal vesicles), such as the sphincter, rectum and/or wall of the pelvis.

T4a: Invades bladder neck, external sphincter, or rectum.

T4b: Invades muscles and/or pelvic wall.


Regional Lymph Nodes (N)

To see if the cancer has spread to the lymph nodes or bones, the doctor may order a CT scan or an MRI of the pelvis and a bone scan.

Sentinel lymph nodes in the pelvis that look suspicious on CT scan or MRI can be examined by fine needle aspiration biopsy method. This is done commonly in breast cancer staging.

NX: Nodes cannot be assessed

N0: No regional node metastasis

N1: Single node metastasis, 2 centimeters (cm) or less at largest point

N2: Single node metastasis, 2 cm to 5 cm at largest point, or multiple nodes, no larger than 5 cm at largest point

N3: Metastasis larger than 5 cm in any node


Distant Metastasis (M)

MX: Metastasis cannot be assessed

M0: No distant metastasis

M1: Distant metastasis

M1a: Distant lymph node(s) involved

M1b: Bone(s) involved

M1c: Other site(s) involved (e.g. liver, lung)


Note on stages that "cannot be assessed."

Patients in whom abnormal digital rectal examinations (DREs) do not match up with their prostate biopsy findings are "clinically unstageable."

To find out what unstageable prostate cancer involves, Wisconsin researchers looked at post-op pathology reports of some 100 patients who were unstageable.

"For these patients pathological staging revealed pT2a cancers in 26%, pT2b in 53%, pT3a in 19%, pT3b and pT0 in 1% of patients." The authors conclude: "Thus, the prevalence of unstageable prostate cancer is low but significant and it can be accurately classified into clinical stage T1c. "Clinical and pathological characteristics of unstageable prostate cancer: analysis of the CaPSURE database. Langenstroer P et al. Medical College of Wisconsin. J Urol. 2005 Jul;174(1):118-20.