Systemic Therapies

Men with metastatic prostate cancer (which has spread to the lymph nodes or other parts of the body) have more treatment options than ever before. Better understanding of the biology of prostate cancer has led to the recent development of several new medications that are helping men survive longer and enjoy a good quality of life. This is true both if you have metastatic disease at the time you’re initially diagnosed as well as if you develop metastatic prostate cancer after undergoing radical prostatectomy or radiation therapy.

Since 2010, six treatments have been shown to prolong the lives of men with metastatic prostate cancer, and the FDA has already approved four of these. Many other systemic therapies are in the late stages of development.

Drugs used to manage metastatic prostate cancer are called systemic therapies because they circulate throughout the body to attack cancer cells wherever they may be. Our medical oncologists are experts at determining which of the following treatments or combination of treatments will be most effective for you, considering the specific features of your disease.

We know that the male sex hormone testosterone (an androgen) stimulates the growth of prostate cancer cells. Hormone therapy (also known as androgen-deprivation therapy) includes a variety of medications that reduce this effect by decreasing the production of testosterone or blocking the binding of testosterone to cancer cells. Hormone therapy can shrink and slow the growth of prostate tumors, even after the cancer has spread to distant sites in the body. We may recommend hormone therapy if one of the following applies to you:

  • You have locally advanced disease that hasn’t spread to other parts of the body.
  • You have a high Gleason score or high prostate PSA level and are receiving radiation therapy.
  • You’ve been diagnosed with metastatic disease.

Hormone therapy can effectively shrink and control the spread of prostate cancer in many men. After a period of months or years, however, many prostate tumors become resistant to first-line hormone therapy. These first-line therapies are designed to reduce a man’s testosterone to “castrate levels” — in other words, to a level that is similar to what is achieved with the removal of the testicles. Men who no longer respond to first-line hormone therapy are therefore said to have castration-resistant prostate cancer. To delay the onset of castration resistance, we may recommend that you receive first-line hormone therapy intermittently, meaning that you take it long enough to reduce your PSA level and control cancer growth, then intentionally stop it for a period of time to reduce side effects, such as hot flashes and erectile dysfunction. Hormone therapy is then restarted if and when the cancer starts to regrow.

Men with castration-resistant prostate cancer have more options than ever before.

Our medical oncologists led a large-scale, international clinical trial of a new, highly potent hormone therapy called abiraterone acetate (Zytiga). This drug blocks a key enzyme involved in testosterone production, lowering the level of testosterone in the tumor and in the bloodstream. The drug has been shown to prolong survival in men with cancers that have progressed despite treatment with other hormone therapies and with chemotherapy.

We’re also developing several new drugs that directly block signaling by the androgen receptor, which can continue to stimulate the growth of prostate cancers when testosterone is at the castrate level. One of these investigational drugs, called MDV3100, was discovered by an MSK scientist. MDV3100 specifically binds to androgen receptors in cancer cells, blocking the ability of the receptor to drive cancer growth. In a recently reported international clinical trial led by MSK medical oncologists, MDV3100 was shown to prolong survival in men with prostate cancers that have progressed after treatment with hormones and chemotherapy.

Research has shown that these drugs improve survival in men with metastatic prostate cancers that do not respond to other treatments.

Chemotherapy is medication that is given intravenously or by mouth to kill cancer cells. It’s an important treatment option for men with prostate cancer that has spread (metastasized) after hormone therapy, and it has been shown to prolong survival and reduce pain in men who have cancer that has spread to their bones. Docetaxel (Taxotere®), which damages the structure of prostate cancer cells, is considered the standard of care in chemotherapy for men with prostate cancer that is resistant to hormone therapy.

The FDA also approved the chemotherapy drug cabazitaxel (Jevtana®) for treating metastatic prostate cancers that have progressed in patients taking docetaxel. Cabazitaxel inhibits the growth of cancer cells.

Immunotherapy, including therapeutic vaccines and other biologic approaches, harnesses the power of the immune system to selectively target cancer cells.

The first-ever FDA-approved immunotherapy treatment for men with advanced metastatic prostate cancer was sipuleucel-T (Provenge®). The drug is made by harvesting a person’s immune system cells, engineering them to fight prostate cancer cells, and putting them back into the body. It has been shown to extend survival for men with metastatic prostate cancer.

Other immunotherapies are being developed at MSK to help lengthen the lives of these men.

When prostate cancer becomes advanced and spreads (metastasizes) throughout the body, it can cause pain and other symptoms. These symptoms can also occur during hormone therapy, when your level of testosterone is very low.

One of the most common sites of prostate cancer metastasis (that is, an area to which it spreads) is the bones. Bone-targeting treatments can help by reducing tumor cells’ ability to thrive in your bones, among other actions.

Medicines to help prevent bone pain and fractures in men with metastatic prostate cancer include:

  • zoledronic acid (Zometa®), a bisphosphonate
  • denosumab (Xgeva®), which blocks a molecule involved in the formation of bone abnormalities caused by prostate cancer and is used to prevent bone complications