PSA Rising During Hormone Therapy

This section summarizes key points to consider when your PSA is rising while undergoing hormone therapy. The list is by no means exhaustive, and there might be other points that you want to think about as well. The goal is to help you focus on what you need to know about each stage of disease so you can hold meaningful, regular dialogues with all members of your health care team as you find the treatment path that’s right for you.

  1. A rising PSA during hormone therapy doesn’t mean you’re out of options—it means you need to consider the use of other systemic therapies such as chemotherapy, alternative hormonal medications, or agents that target the spread of prostate cancer (metastasis). Some of these options may be available through clinical trials. This field is constantly changing with new drug and cancer vaccine approvals expected in 2010-11, so consulting with your doctors about some of these newer therapies is encouraged.
  2. When your cancer is progressing despite a low level of testosterone in the blood (a blood test can check this, and it should be less than 50 ng/dl while on testosterone lowering therapies), we term this state castration-resistant, or androgen-independent, or hormone-refractory prostate cancer. However, some hormonal therapies can still work in this setting, including bicalutamide, flutamide, nilutamide, ketoconazole, steroids, and DES. Your doctor should decide if these are right for you based on the risks and benefit of each of these medications. Bicalutamide, flutamide, and nilutamide work by blocking testosterone’s receptor, while ketoconazole lowers testosterone even further by reducing the adrenal gland’s production of testosterone. DES is an estrogen that can lower testosterone and has anti-cancer activity. Finally, steroids can be sometimes useful by themselves to control pain and reduce the PSA for a period of time. In general, however, most of these medications only work for a relatively short period of time, on the order of 3-5 months on average, so planning for the future and other treatments remains important.
  3. The primary goal of chemotherapy is to stop the cancer cells from dividing and the cancer cells from growing. But when we look at whether a drug is working, there are generally two levels of effectiveness—whether a drug is palliative, meaning whether it can alleviate symptoms, and whether it can affect the cancer cell growth significantly enough to prolong life. Sometimes chemotherapy can do both of these things, and how much chemotherapy will benefit a man is very individualized based on their individual profile. It is important to see a medical oncologist early in your disease course so that these treatment options can be considered in a timely manner.
  4. The benefits of chemotherapy in prostate cancer were only first realized recently: estramustine (Emcyt) has been around for several decades as a palliative therapy for men with prostate cancer; mitoxantrone (Novantrone) was approved by the FDA in 1996 when it was shown to provide palliative benefit to men with advanced prostate cancer; docetaxel (Taxotere) was approved in 2004 when it was shown to prolong the lives of the men who took it and relieved symptoms better than mitoxantrone.
  5. Although all chemotherapy drugs are designed to slow or stop the growth of cancer cells, each one tends to work in a slightly different way. However, we do not know if combining chemotherapies provides a greater benefit to men with prostate cancer and this may increase toxicities. Currently, the standard of care is to treat with one chemotherapy first (usually docetaxel and prednisone), followed by additional therapies when docetaxel stops working. There are many ongoing clinical trials looking at adding experimental medications to docetaxel to make docetaxel work better and prolong life and quality of life. We encourage you to discuss whether a clinical trial is right for you with your doctors.
  6. Pay close attention to your reactions to the different chemotherapy drugs. You’re the only one who really knows your own body, so you’re the only one who can know whether you are able to tolerate a particular treatment regimen. Typically, low dose prednisone is given with docetaxel and mitoxantrone to help with the tolerability of chemotherapy. However, prednisone has several side effects as well that you should be aware of, including sleep problems, increased appetite and weight, thinning of the skin, upset stomach, accelerated bone loss and fracture risk, and infections.
  7. Don’t be too tough or “macho.” There are plenty of drugs available to help ward off (prevent) or treat the different side effects of chemotherapy, especially to prevent nausea and vomiting.
  8. Focus on yourself. It doesn’t matter what you do, as long as it can help you relieve stress and can help you with the most important part of your cancer treatment—getting well. Having a strong social support network through family and friends will help with your ability to fight your cancer. Prostate cancer support groups around the country can also provide this needed support. Ask your doctor about one in your area.
  9. Prostate cancer cells that have spread beyond the prostate seem to prefer bone tissue and tend to migrate there after escaping the pelvic region. Once the cells settle in, they’re known as prostate cancer bone metastases. Unlike bone cancer, which originates in the bone, prostate cancer bone metastases are actually collections of prostate cancer cells that happen to be sitting within the bones.
  10. When prostate cancer cells settle in the bones, they interact with the bone cells, causing new bone cells to grow and causing the bone tissue to break down. The dye-like material that’s injected during a bone scan highlights areas of bone metabolism or activity—areas where bone tissue is changing more rapidly than it normally would in a healthy adult male.
  11. Men who experience pain from a bone metastasis will often be treated with radiation targeted directly to the metastasis or with radiation-emitting drugs that settle in the metastasis after being injected through a vein. The radiation will kill the prostate cancer cells in the metastasis and thereby relieve the pain.
  12. Bisphosphonates are drugs that are designed to help reset the balance in the bone between bone growth and bone destruction which is disrupted by the prostate cancer bone metastases. Zoledronic acid (Zometa) is a bisphosphonate given intravenously that can delay the onset of complications associated with prostate cancer bone metastases and relieve pain. It is typically given once every three weeks as a 15-minute infusion. Less frequent schedules are sometimes used as well depending on your individual circumstance and risk. There are some risks with zoledronic acid including something called osteonecrosis of the bone (ONJ) that can occur after deep dental procedures and extractions or sometimes spontaneously. This results in sometimes jaw pain and poor healing of your teeth.
  13. As the bones in the spine weaken, they can collapse one of top of the other, compressing the spinal cord and the nerves that run out from it. Spinal cord compression associated with metastatic prostate cancer can cause serious problems if not managed immediately, so be sure to tell your doctors about any new pain, weakness, or changes in bowel habits, any of which can result from spinal cord compression. Steroids and radiation are used if this occurs.
  14. Cancer can be painful, and there’s no benefit in acting stoic and pretending it doesn’t affect you. There are plenty of very effective pain medications available, and using them will allow you to feel better and stay stronger.
  15. Don’t assume that you can’t get pain relief unless you’re completely doped up. Some very simple and easy to take oral medications might be enough to ease your pain without causing you to lose your focus and ability to work and function.
  16. Don’t worry about becoming addicted to pain medication. Taking pain medications so that you can spend your days feeling healthier and stronger is the opposite of addictive behavior. However, both physical dependence and tolerance are possible as your body starts to get used to the drugs, so you and your doctors should take them into consideration as you start and stop different pain medications.
  17. Consider enrolling in a clinical trial of an experimental new treatment or regimen. Clinical trials are the only way that new and better treatments will be developed and tested appropriately. Clinical trials are the reason that we have effective therapies for prostate cancer today, and there are many more effective therapies out there to explore.

Terms to know from this article:


A chemical made by glands in the body. Hormones circulate in the bloodstream and control the actions of certain cells or organs. Some hormones can also be made in a laboratory.


The spread of cancer from one part of the body to another. A tumor formed by cells that have spread is called a "metastatic tumor" or a "metastasis." The metastatic tumor contains cells that are like those in the original (primary) tumor. The plural form of metastasis is metastases (meh-TAS-ta-seez).


A hormone that promotes the development and maintenance of male sex characteristics.


A type of hormone that promotes the development and maintenance of male sex characteristics.


In medicine, describes a disease or condition that does not respond to treatment.


An anticancer drug that belongs to the family of drugs called anti-androgens. Flutamide use has been largely replaced by newer anti-androgen drugs including Enzalutamide.

Adrenal Gland

A small gland that produces steroid hormones, adrenaline, and noradrenaline, which help control heart rate, blood pressure, and other important body functions. There are two adrenal glands, one located on top of each kidney.  


A hormone that promotes the development and maintenance of female sex characteristics.


Designed to produce relief from symptoms without curing, e.g., aspirin for a headache is palliative.


A doctor who specializes in treating cancer. Some oncologists specialize in a particular type of cancer treatment. For example, a radiation oncologist specializes in treating cancer with radiation.

Docetaxel (TAXOTERE)

Docetaxel is the first FDA-approved chemotherapy for advanced prostate cancer. This medicine is in a class of medications called taxanes. It works by blocking cell division which results in cancer cell death.

Bone scan

A technique to create images of bones on a computer screen or on film. A small amount of radioactive material is injected into a blood vessel and travels through the bloodstream; it collects in the bones and is detected by a scanner.

Zoledronic acid (Zometa)

An FDA approved treatment for bone complications in patients with bone-metastatic cancer, including castrate resistant prostate cancer. Zoledronic acid belongs to a class of drugs called bisphosphonates, which slows the process of bone breakdown and reabsorbption.


prostate-specific antigen (PSA): A substance produced by the prostate that may be found in an increased amount in the blood of men who have prostate cancer, benign prostatic hyperplasia, or infection or inflammation of the prostate.