Advanced Prostate Cancer
Hormone therapy
Hormone therapy, also known as androgen deprivation therapy (ADT), usually involves medication to reduce the level of certain hormones in the body or block their effect. Prostate cancer relies on male hormones called androgens – such as testosterone – to grow. Most testosterone is made in the testicles, but the adrenal glands also make small amounts of androgens. ADT blocks production of these hormones, stunting the growth of the tumor. ADT is often given long-term, so some doctors suggest an intermittent schedule if the side effects are substantial. In those cases, treatment will be given for six to 12 months to suppress the cancer and lower PSA levels, and is then stopped and restarted when the PSA levels reach a specific level defined by your doctor. (The effectiveness of intermittent therapy vs. continuous treatment is uncertain, so talk to your doctor to learn more.) Follow-up visits are typically every three to six months to discuss symptoms and to measure your PSA level.
ADT options
One category of ADT drug is known as luteinizing hormone-releasing hormone (LHRH) agonists; these agents prevent the testicles from making testosterone. Another category known as an LHRH antagonist works in a similar way and may be used in certain situations. Given as an injection, either type results in what is sometimes called “medical castration.” Another way to reduce the testosterone level is to surgically remove the testicles. However, this treatment option, known as “surgical castration,” is not more effective than treatment with an LHRH agonist or antagonist. (See Table 1.)
Table 1. Hormone therapy options for advanced prostate cancer
| Type of treatment | Drug |
| LHRH* agonists (medical castration) |
goserelin (Zoladex)
histrelin (Vantas)
leuprolide (Eligard, Lupron, Viadur)
triptorelin (Trelstar)
|
| LHRH antagonist |
degarelix (Firmagon)
|
| Surgical castration | Bilateral orchiectomy (removal of both testicles) |
| Antiandrogens (androgen receptor inhibitors) |
bicalutamide (Casodex)
enzalutamide (Xtandi)
flutamide (Eulexin)
nilutamide (Nilandron)
|
| Androgen synthesis inhibitor |
abiraterone (Zytiga)
|
| Gonadotropin-releasing hormone (GnRH) receptor antagonist |
relugolix (Orgovyx)
|
Sometimes an antiandrogen drug is combined with either an LHRH agonist drug or surgical castration in a treatment strategy called combined androgen blockade or total androgen blockade, but studies have shown that, in the long run, this approach offers no additional benefit over either method of castration alone in men with metastatic disease. Occasionally, antiandrogens are temporarily combined with LHRH agonists to block the brief rise of testosterone that occurs right after the injection.
Eventually, ADT will stop being effective, and the cancer will begin to progress (grow). When this happens, the cancer is said to be “hormone refractory” or “castration resistant.” Treatments available for castration-resistant prostate cancer include hormone therapy, chemotherapy and immunotherapy, depending on the extent of disease and whether symptoms are present. Chemotherapy is the recommended option for men with castration-resistant prostate cancer who also have symptoms, whereas immunotherapy is recommended for men who have no or minimal symptoms. Two hormone therapy drugs have both been shown to be beneficial for men with castration-resistant prostate cancer.
- Abiraterone (Zytiga) and enzalutamide (Xtandi) are both approved by the FDA for the treatment of castration-resistant prostate cancer either before or after chemotherapy.
Researchers continue to evaluate different combinations of chemotherapy and/or immunotherapy drugs to further improve survival and the time to disease progression.
Side effects
Among the most common side effects of ADT is a loss of bone mass (known as osteoporosis). This occurs when the bone cells that help rebuild bone (osteoblasts) are not replaced at the same rate as cells that naturally break down bone (osteoclasts). As a result, bones become thin and porous (full of tiny holes) and are more likely to fracture (break) or cause pain and disability. Drugs known as bone-modifying agents can be used to prevent or manage osteoporosis in men receiving ADT. The bone-modifying agents used to prevent or manage osteoporosis related to ADT are also used to treat bone metastases.
Other side effects of ADT are treatable, and many may stop once treatment is finished. Men who receive long-term ADT often experience side effects that last more than a year after the drug is discontinued, and for some of these men, side effects may never go away. Among the most common side effects of ADT are:
- Hot flashes or flushes
- Night sweats
- Loss of sex drive and ability to achieve/maintain an erection
- Weight gain
- Fatigue
- Loss of muscle mass
- Mood changes, irritability
- Enlargement or tenderness of breasts
Some studies have found that ADT may be associated with a greater risk of heart disease and diabetes. For this reason, you should have regular checkups with your family physician and follow a healthy diet and exercise plan. More information on managing treatment-related side effects is provided here.
Side effects from surgical castration are permanent; for example, sterility (inability to produce children) is a result that cannot be reversed.
Monitoring response
If you receive ADT, your doctor will see you at regular follow-up visits to evaluate how well the treatment is working. If the cancer is locally advanced, a medical history and physical examination along with a DRE and PSA test are done every six to 12 months. If the cancer has spread to lymph nodes or metastasized to other parts of the body, you will have a physical exam that includes a DRE and a PSA test every three to six months, and periodic imaging studies (e.g., CT, bone scan or MRI) may be completed. If your PSA level begins to rise steadily, the “PSA doubling time” is often calculated. This calculation is the time it takes for your PSA to increase to twice its level, and it is useful for predicting outcomes, such as the time until the cancer appears in a new site. If your PSA level rises or fails to fall, other studies will be done to determine if the cancer has spread.
Questions about hormone therapy you may want to ask your doctor
- What are my options for hormone therapy and what do you recommend?
- What are the risks and benefits of different hormone therapies?
- How will I know if hormone therapy is working?
- If hormone therapy does not work, are there other options?
- What side effects can I expect?
- Will the side effects go away?
- How will treatment affect my sexual well-being and fertility?
- When will I begin treatment? How often will I have treatments? When will I finish treatment?
- How will I know if treatment is working?
- What can I do to take care of myself during treatment?
- How often will I need checkups?
- What is the cost of hormone therapy and will insurance cover it?
- Is there a clinical trial that I may be eligible for?
