Prostate Cancer (cont.)
What is Hormone Therapy?
Prostate cells are physiologically dependent on male hormones called androgens. Androgens cause hormonal stimulation of the prostate cancer cells causing them to grow, function, and proliferate. Testosterone, although not directly carcinogenic, is essential for the growth and perpetuation of tumor cells. The testes are the source of most androgens. The goal of hormonal therapy is to lower levels of testosterone or to stop testosterone from working. This can be achieved with surgery or with drug treatment. Often, the initial response is good, but cancer may progress over time.
Androgen deprivation therapy: This therapy is likely to be used in cases in which the cancer has spread to distant regions. Therefore, it is not currently used among the standard options for men with localized prostate disease. It may be added to surgery and radiation in cases at high risk for relapse due to high Gleason score and/or positive surgical margins.
- The testes produce much of the testosterone that stimulates cancer growth. Surgical removal of both testicles (castration, or orchiectomy) is the best way to stop hormonal stimulation of the tumor.
- Men usually prefer medical castration to surgical castration as it is temporary and reversible, albeit much more expensive. A variety of agents have been used to suppress androgen levels acting at different levels of hormonal production and release.
- Nowadays, GnRH agonists are the most widely used. They induce a medical castration by suppressing luteinizing hormone production and, therefore, the synthesis of testicular androgens. A number of GnRH agonists are available (leuprolide, goserelin, buserelin, and triptorelin).
- GnRH antagonists (degarelix) may be beneficial in cases when immediate decrease in testosterone levels is required.
- Estrogen, in the form of diethylstilbestrol, can also be used to suppress testosterone. Because of its extensive side effects, estrogen is not used very often.
- Antiandrogen monotherapy: Antiandrogens bind to androgen receptors and competitively inhibit their interaction with male hormones (testosterone and dihydrotestosterone).
- Unlike medical castration, antiandrogen therapy does not decrease luteinizing hormone (LH) levels and androgen production. Rather, testosterone levels are normal or increased. Thus, men treated with antiandrogen monotherapy do not have the full spectrum of side effects attributable to low levels of testosterone, and many maintain some degree of potency.
- These agents are usually used in combination with a GnRH agonist either continuously or for 2 to 4 weeks during the initiation of treatment with a GnRH agonist. This is also known as "complete androgen blockade."
- The most common agents are flutamide (Eulexin), bicalutamide (Casodex) and nilutamide.
- Drugs that stop the adrenal glands from making androgens are sometimes used.
- Side effects of these medications vary. Orchiectomy and LHRH agonists may cause impotence, hot flashes, and loss of sexual desire, osteoporosis, and bone fractures. Antiandrogens may cause nausea, vomiting, diarrhea, and breast enlargement or tenderness. Any of these therapies can weaken bones.
Prostate Cancer Follow-up
Follow-up care is especially important for patients who opted for a more conservative approach (such as watchful waiting) to treat prostate cancer. It is imperative that a man see his urologist for digital rectal exams, PSA level tests, and other tests as recommended to follow the progression of cancer growth.
For men who have undergone radical prostatectomy, radiation therapy, or both, follow-up care is important to prevent cancer recurrence.
- PSA has been shown to be useful in detecting recurrences. PSA levels should be less than 0.2 ng/mL after radical prostatectomy.
- PSA levels should be checked every 3 months for 1 year, every 6 months for the second year, and annually after that.
- A man should have a physical examination, including digital rectal exam, every 3 months for 1 year, then every 6 months for a year, then yearly after that.
- In certain cases after radical prostatectomy, additional treatment may be required based on the final pathology report of the removed prostate or if the PSA starts increasing after surgery.
- This may be in the form of additional radiation treatment to the area where the prostate once was and/or hormonal treatment with LHRH agonists or antiandrogens as mentioned earlier.
How to Prevent Prostate Cancer
The high lifetime risks of prostate cancer development, the morbidities associated with treatment of established prostate cancer, and the inability to eradicate life-threatening metastatic prostate cancer offer compelling reasons for prostate cancer prevention.
However, because the cause of prostate cancer is uncertain, preventing prostate cancer may not be possible. Certain risk factors, such as age, race, sex, and family history, cannot be changed. Nevertheless, because diet and other lifestyle factors have been implicated as a potential cause, living a healthy lifestyle may afford some protection.
- Proper nutrition, such as limiting intake of foods high in animal fats and increasing the amount of fruits, vegetables, and grains, may help reduce the risk of prostate cancer.
- The following supplements should NOT be used to prevent prostate cancer:
- Vitamin E
- Vitamin C
5-alpha reductase Inhibitors (5-ARI):
- Using 5-ARIs for prostate cancer is controversial.
- Initial studies have shown that finasteride decreased the risk of developing prostate cancer by 25% (Prostate Cancer Prevention Trial). However, initial reports indicated that, while fewer cases of low and intermediate grade prostate cancer did develop resulting in about a 25% lower risk of developing prostate cancer overall, high-grade prostate cancer was more likely to occur in men treated with finasteride. Even though this increased risk with finasteride may be due to a selection bias, there is no proof that finasteride would not increase the true incidence of high-grade cancer.
- In the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) trial, dutasteride decreased the risk of developing Gleason score 5 to 6 cancer but not Gleason 7 to 10 cancer.
- In both trials 5-ARIs increased the risk of erectile dysfunction and loss of libido.
- Although it is possible that 5-ARIs reduced the risk of being diagnosed with prostate cancer, it is unknown if this will translate into reduced mortality.
- 5-ARIs are not FDA approved for the prevention of prostate cancer.
Medically Reviewed by a Doctor on 11/21/2017
Pierre-Alain Hueber, MD, PhD
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