Articles on Prostate Cancer
How does hormonal therapy affect prostate cancer?
Prostate cancer is highly sensitive to, and dependent on, the level of the male hormone testosterone, which drives the growth of prostate cancer cells in all but the very high-grade or poorly-differentiated forms of prostate cancer. Testosterone belongs to a family of hormones called androgens, and today front-line hormonal therapy for advanced and metastatic prostate cancer is called androgen deprivation therapy (ADT).
What is androgen deprivation therapy (ADT)?
In the past, this was accomplished by surgical castration called bilateral orchiectomy. In that procedure, the testes were both removed. Today, doctors can block the function of the testes in a controllable and most often reversible fashion with drugs that prevent the production of testosterone (medical castration). These agents can result in shrinkage of the prostate gland, can stop prostate cancer cells from growing for up to several years, and can relieve pain caused by prostate cancer that has spread or metastasized into the bones by shrinking the cancer. The use of ADT does not produce a cure. Over time, the prostate cancer cells will develop an ability to grow despite the lack of hormones (castrate resistance). Another form of hormonal therapy is the use of androgen receptor blockers; these medications prevent testosterone from attaching (binding) to the prostate cancer cell and being absorbed into the cell where it can help the cell survive and grow.
Hormonal treatment today is primarily used in the treatment of locally advanced and metastatic prostate cancer. It may be used in conjunction with primary curative therapies (surgical and radiation based) to shrink the cancer/prostate to increase the likelihood of cure of the treatment, neoadjuvant therapy, and with radiation therapy for several years after treatment (adjuvant therapy). However, the primary role of ADT is in the treatment of widespread or metastatic prostate cancer. While it is not a curative treatment in that setting, it can both reduce symptoms and slow down the growth of the prostate cancer to prolong life.
What medications block testosterone for prostate cancer treatment?
Today medicines used to block testosterone production by the testes include:
- LH-RH agonists: Leuprolide (Lupron), goserelin (Zoladex), histrelin (Supprelin LA), and triptorelin (Trelstar) are examples of these mediations. These are either given by injection into the muscle or under the skin at varying intervals of at least 1 month or longer.
- LH-RH antagonists: Degarelix (Firmagon) is a monthly injection that is given under the skin.
Medications that block the action of testosterone include the androgen receptor blockers
Flutamide (Eulexin), bicalutamide (Casodex), nilutamide (Nilandron), and an even more effective form called enzalutamide (Xtandi): Xtandi is recommended for use only in individuals with castrate-resistant prostate cancer (prostate cancer that is refractory to traditional ADT), including those with and without metastases. Xtandi is different than the other androgen receptor blockers in that it has three mechanisms of action:
- It prevents androgens (testosterone) from binding to the androgen receptor,
- it prevents the androgen receptor from moving into the central area (nucleus) of the cell, and
- it prevents binding of the androgen receptor to DNA and stimulating growth.
The most common side effects of Xtandi include
- back pain,
- decreased appetite,
- hot flush,
- upper respiratory tract infection,
- swelling of the legs,
- shortness of breath with exertion,
- dizziness, and
- weight loss.
Less commonly, seizures and posterior reversible encephalopathy syndrome characterized by seizure, headache, lethargy, confusion, and blindness may occur. A newer androgen receptor blocker with a similar mechanism of action as Xtandi, apalutamide (Erleada), is indicated for use in men with nonmetastatic castrate resistant prostate cancer.
Both surgical and medical castration result in impotence. They also can cause hot flashes, fatigue, anemia, and thinning of the bones (osteoporosis) over time. These drugs may be given individually or combined with an androgen receptor blocker in what is called a combined androgen blockade.
Other hormonal treatment options include:
Estrogen: This female hormone has been utilized in the treatment of prostate cancer as it also results in medical castration. Its mechanism of action remains under study, and its association with a high risk of heart attack and blood clots when used in high doses has diminished the frequency of its use, particularly in front-line therapy. Other side effects include breast enlargement/pain (gynecomastia). Estrogen and related drugs may still have a role in the treatment of metastatic prostate cancer in select individuals.
Adrenal androgen synthesis inhibitors: The adrenal glands, a pair of small glands that are located above the kidneys, also produce a small amount of testosterone. Individuals on traditional ADT have testicular production of testosterone suppressed but still may have testosterone production from the adrenal glands. In individuals on ADT who have continued growth of the prostate cancer (rising PSA), the use of adrenal androgen synthesis inhibitors may be useful. This group includes a drug called ketoconazole, which was primarily developed to treat fungal infections, but has shown to be effective in the treatment of prostate cancer. More recently, an agent called abiraterone acetate (Zytiga) has been developed. It has a similar effect on androgen synthesis, but it is more powerful than an older agent called ketoconazole (Nizoral) and has fewer side effects. The use of Zytiga in combination with prednisone is considered in individuals failing traditional ADT and individuals who have castrate-resistant prostate cancer (failed first-line ADT). More common side effects of Zytiga include fatigue, back or joint discomfort, peripheral edema, diarrhea, nausea, constipation, and low potassium levels. Blood pressure, liver tests, potassium, and phosphate levels should be monitored regularly when initially using Zytiga.
Steroids: These agents including prednisone may have beneficial hormonal effects in prostate cancer, including slowing the production of androgen by the adrenal glands. They often make the patient feel better, but have many side effects including inducing or worsening diabetes, fluid retention, cataract formation, weight gain, and osteoporosis.
Agents that block the conversion of testosterone to its active metabolite: Finasteride (Proscar) and dutasteride (Avodart) are not approved by the Food and Drug Administration (FDA) for the treatment of prostate cancer, however, they have been used (off-label) in treating prostate cancer by preventing the conversion of testosterone to its active metabolite called DHT (dihydrotestosterone). These drugs are frequently utilized for the symptoms of prostate enlargement in men without prostate cancer and appear to reduce the risk of development of prostate cancer. Their side effects are limited. They are used in combination with other agents to optimize androgen blockade.
Health Solutions From Our Sponsors
American Cancer Society (ACS). <http://www.cancer.org/cancer/prostatecancer/index>.
American Urological Association. "Clinically Localized Prostate Cancer: AUA/ASTRO/SUO Guideline." 2017. <http://www.auanet.org/guidelines/clinically-localized-prostate-cancer-new-(aua/astro/suo-guideline-2017)>.
Byrd, E.S., et al. AJCC Cancer Staging Manual, 7th Ed. New York, NY: Springer, 2009.
The James Buchanan Brady Urological Institute. Johns Hopkins Medicine.
Lu-Yao, G.L., P.C. Albertson, D.F. Moore, et al. "Fifteen-year outcomes following conservative management among men aged 65 years or older with localized prostate cancer." Eur Urol 68.5 (2015): 805-811.
Mottet, Nicolas, et al. "Updated Guidelines for Metastatic Hormone-Sensitive Prostate Cancer: Abiraterone Acetate Combined With Castration Is Another Standard." European Urology 73 (2018): 316-321.
National Comprehensive Cancer Network
"Prostate Cancer." Memorial Sloan Kettering Cancer Center.
Top Prostate Cancer Treatment Hormonal Therapy Related Articles
At What Stage of Cancer is Chemotherapy Used?The decision to use chemotherapy may vary depending on the aggressiveness, stage and type of cancer. Usually, chemotherapy may be used for all stages in most cancer types. Chemotherapy is a type of medicine or combination of medications that is used to treat or kill cancer cells.
Can Prostate Cancer Be Completely Cured?Prostate cancer is the second most common cancer in men. Due to routine screening of prostate-specific antigen (PSA) levels in the United States, nearly 90% of prostate cancers get detected in early stages. When found early, there are several treatment options available and prostate cancer has a high chance of getting cured.
Early-Stage Prostate Cancer Treatment
If prostate cancer is detected early and appears to be slow-growing, invasive procedures, chemotherapy, radiation and other approaches can sometimes do more harm than good. Many prostate cancer treatments come with side effects, like incontinence or impotence, so it’s in the patient’s interest to put off invasive treatments as long as is medically safe. Active surveillance is where doctors "watch and wait" for changes that could prompt medical intervention.
How Can a Man Tell if He Has a Hormonal Imbalance?What is a hormonal imbalance? Learn the signs of hormonal imbalance in men and what to do if you suspect you have a hormonal imbalance.
How Is Prostate Cancer Diagnosed?
Prostate cancer is largely a disease of men over 40, so it’s around this age doctors recommend the first prostate screening. The first exam is a blood test to determine if there are abnormal prostate specific antigen (PSA) levels in your blood – PSA is produced by the prostate. If the PSA is high, your doctor will perform a digital rectal exam, during which the doctor feels your prostate from inside your rectum with a gloved finger. Other diagnostic tests include an endoscopic biopsy of tumor tissue for analysis in a lab.
Prostate CancerProstate cancer is the most common cancer in men after skin cancer. Risk factors include age, family history, ethnicity, and diet. Prostate cancer is diagnosed by digital rectal exam, prostate specific antigen (PSA) test, and prostate biopsy. Symptoms may include frequent need to urinate, incontinence, pain, blood in the urine, fatigue, and more. Prognosis and treatment depend on cancer staging. Watchful waiting, surgery, radiation, cryotherapy, and other management strategies are available. Research and clinical trials strive to find new and better treatments for prostate cancer.
Prostate Cancer Facts
Prostate cancer is a leading cause of cancer and cancer death in males; in some men, identifying it early may prevent or delay metastasis and death from prostate cancer. The prostate is a walnut-shaped gland that is a part of the male reproductive system that wraps around the male urethra at it exits the bladder. Prostate cancer is common in men over 50 years of age, with the risk of developing prostate cancer increases with aging.
Prostate Cancer (Prostatic Cancer) Symptoms and Causes
Difficulty with urination – frequency, weak stream, trouble getting started, etc. – is usually the first sign of prostate cancer. But these and other early symptoms of prostatic cancer can also come from benign prostate conditions, so diagnostic testing is important, including PSA tests and digital rectal exam.
Prostate Cancer Treatment: Radical Prostatectomy Surgery
Radical prostatectomy, or surgical removal of the entire prostate gland, isn’t typically the first choice in prostate cancer treatment. Sometimes a radical approach is necessary to keep the cancer from metastasizing, however. Some cases are too severe or diagnosed too late for drugs or radiation to have much effect. In these cases, treatment teams may opt for a radical prostatectomy, despite potential side effects like impotence and incontinence.
Prostate Cancer Staging and Prognosis
The prognosis for prostate cancer, as with any cancer, depends on how advanced the cancer has become, according to established stage designations. The patient's PSA score at diagnosis, as well as their Gleason score (the grading system used to determine the aggressiveness of prostate cancer) determines the prognosis and final stage designation. Prostate cancer has a high survival rate in general, but your chances depend on the stage of the cancer.