Throw us a bone

by Donna Canada, RN, CURN

Hormone therapy/ADT (androgen deprivation therapy) for prostate cancer is a treatment to decrease the level of male hormones in the body. Hormonal therapy is the primary treatment for older men with prostate cancer who don't want surgery or forms of EBRT but also don't want active surveillance (to watch and wait). This modality is also used for men with metastatic disease when their original treatment failed to eradicate the cancer.

Walsh states: "even when cancer has escaped the prostate, there is still much hope—more now than ever before." The mainstay for the management of advanced disease is hormonal therapy-shutting down the hormones that feed the prostate and nourish the cancer.

Unfortunately, some prostate cancer cells aren't affected by hormone therapy at all. These are called hormone-resistant (or androgen independent) cells. Prostate cancer can become androgen independent over time.

When ADT treatment begins, the early results are typically successful and highly encouraging. The tumor shrinks, the PSA drops, and the patient feels better. Only the hormone dependent cancer cells have been affected and the drop in PSA level may be misleading. When the PSA drops, it's a signal that the cancer is responding-which is good; but it's no guarantee that the cancer is completely gone. The cancer cells that are not hormone-dependent are unaffected by ADT. This is described as "hormone refractory."^{3(p 438-439)}

The amount of cancer cell death from ADT in early-stage prostate cancer is usually dramatic. On rare occasions, no cancer at all can be found in the surgically removed prostate glands of men who underwent surgery after ADT. More typically, there is a drastic reduction in the number of cancer cells, but not total elimination. Androgen deprivation therapy also appears to have the ability to put some prostate cancer cells to "sleep."

What all this means is that the effect of ADT on different cells in a prostate cancer tumor can be variable; many of the cancer cells are killed, but others are simply inhibited from growing.⁴

There are several forms of hormonal therapy that can be used individually or in combination. They are all designed to lower testosterone in the blood. The most direct and least expensive way to control testosterone is to surgically remove a man's testicles; this is called an orchiectomy, or surgical castration. The same effect can be accomplished medically with drugs called LHRH (luteinizing hormone-releasing hormone) agonists, LHRH antagonists, or antiandrogens. For obvious reasons, surgical castration is rarely done today.^5(p439)

Modern testosterone-blocking medications work by three primary mechanisms. LHRH agonists such as Lupron or Zoladex are injectable hormonal analogs that reduce luteinizing hormone (LH) causing the testicles to stop testosterone production. Anti-androgen blocking agents such as Casodex, Eulexin and Nilutamide are medications in pill form that work by blocking testosterone access to androgen receptors located inside the cancer cell. Five-alpha reductase inhibitors such as Proscar and Avodart block the conversion of testosterone into dihydrotestosterone, which is a much more potent form of testosterone. These three classes of therapeutic agents can be used either by themselves or in combination.⁴

The advantages and disadvantages of using agents singly or in combination will be covered comprehensively in another article. A typical protocol used for newly diagnosed patients is administering one drug from each class for about one year.

Advantages:

LHRH antagonists:

• Not permanent

Antiandrogen therapy:

• Blocks prostate cell's ability to absorb the hormone but still circulates freely in the blood
• Often used in conjunction with injections
• Most antiandrogens are not effective as a single agent

Orchiectomy:

• A onetime procedure that avoids the need for injections
• Drops testosterone quickly to almost zero
• Permanent

Disadvantages:

LHRH antagonist:

• Can cause a flair of bone pain in those with bone metastases
• Need to pre-treat these men with androgen receptor blocker (antiandrogen)
• Requires monthly to yearly injections
• Expensive

Antiandrogen therapy:

• Diarrhea
• Liver damage
• Impaired night vision

Orchiectomy:

• Involves minor surgery
• Risk of infection, bleeding, pain
• Psychological distress due to cosmetic issues and inability to enjoy sex, which can be dependent on a man's age and stage of illness

For all of the above:

• Loss of muscle mass
• Osteoporosis ("thinning" of the bones)
• Hot flashes
• Decreased libido
• Erectile dysfunction
• Irritability
• Mood swings
• Weight gain
• Increased risk of cardiovascular problems
• Increased risk of diabetes and cardiovascular disease⁹

Second Line Treatment Options: 

• Chemotherapy

References:

1. Ellsworth P. 100 Questions & Answers About Prostate Cancer.2nd ed. Sudbury, MA: Jones and Bartlett Publishers; 2009.
2. American Cancer Society, Bostwick D, Crawford ED, Higano C, Roach M, eds. Complete Guide to .Atlanta, GA: ACS Health Promotions; 2005.Prostate Cancer
3. Walsh PC, Worthington JF. Dr Patrick Walsh's Guide to Surviving Prostate Cancer" 2nd ed. New York, NY: Wellness Central; 2007.
4. Scholz, M. Newly Diagnosed Prostate Cancer: Evaluating The Options -- Part 2 Of 3. CRI Insights [online] August 2003 vol. 6, no. 3, Available at: http://www.prostate-cancer.org/pcricms/node/141#ADT. Accessed on September 11, 2010.
5. Vogelzang, 2010 American Society of clinical Oncology Annual Meeting. August 2010 article: Cabazitaxel New Chemo Approved for Advanced Prostate Cancer. Available at: http://www.ustoo.org/PDFs/HotSheets/HotSheet082010.pdf . Accessed on September 11, 2010.
6. Warde, 2010 American Society of clinical Oncology Annual Meeting. July 2010 article: RT Shown Beneficial for Prostate Cancer Subset. Available at: http://www.ustoo.org/Hot_Sheets.asp. Accessed on September 11, 2010.
7. Crouzet, 2010 American Urological Association Annual Meeting Retrieved from July 2010 article: High Intensity Focused Ultrasound Noninferior to External Beam RT for Prostate Cancer. Available at: http://www.ustoo.org/Hot_Sheets.asp. Accessed on September 11, 2010.
8. MSNBC. FDA approves new drug for prostate cancer (press release). Available at: http://www.msnbc.msn.com/id/36853649/ns/health-cancer/. Accessed September 14, 2010.
9. Galvão, DA; Newton, RU, Taaffe, DR, Spry, N. Can Exercise Ameliorate the Increased Risk of Cardiovascular Disease and Diabetes Associated with ADT? Nat Clin Pract Urol. 2008;5(6):306-30. Available at: http://www.medscape.com/viewarticle/575534. Accessed on September 15, 2010.

This article has been reviewed by a member of the Wellness Partners Editorial Board.

Posted September 2010