Prostate cancer is the most common cancer among U.S. men, though because the cancer grows slowly it doesn't always immediately cause health problems. And there are effective treatments for many people, with several new drugs approved for tougher cases in recent years. Researchers also are exploring genetic tests to decide which therapies are best for which cases, according to Dr. Emmanuel Antonarakis, medical oncologist at the Johns Hopkins Kimmel Cancer Center.
How often does prostate cancer advance and need treatment?
Prostate cancer is among the most common cancers, at more than 200,000 cases diagnosed each year in the U.S. Most prostate cancers are confined to the prostate gland itself and have not spread beyond it. About 70 percent of men with these cancers can be cured with surgery to remove the gland or radiation directed precisely at it. In the remaining 30 percent of men, prostate cancer will recur within 10 years of their initial treatment of the prostate gland. Most men with these recurrent cancers cannot be cured, but their lives can be extended and their cancers can be put into remission with palliative treatments. These treatments do not aim to cure, but rather to improve the quality and length of life.
What are the standard treatments for advanced prostate cancer?
When tests indicate that a prostate cancer patient's level of prostate specific antigen (PSA) is rising or imaging scans indicate cancer in other areas of the body, doctors often first prescribe hormone therapies that block the male sex hormone testosterone, which fuels prostate cancer cells. These therapies work for some time, but most men will eventually develop what's commonly called "hormone-resistant" prostate cancer, which doesn't respond to standard hormone therapy anymore. In the last decade, the U.S. Food and Drug Administration has approved six new drugs for this type of advanced cancer, five of them in the last five years. They include two therapies called enzalutamide and abiraterone, which target testosterone. Other approved therapies are sipuleucel-T, which uses the body's immune system to fight prostate cancer cells; an injectable, liquid radiotherapy called radium-223 that binds to the bone where prostate cancer often spreads; and the chemotherapy drugs, cabazitaxel and docetaxel.
How and when do patients become resistant to standard treatments?
Remissions in men with advanced prostate cancer last approximately 18 to 24 months. When men become resistant to hormone therapy, it's because prostate cancer cells engineer ways to make their own fuel source — testosterone — or change their structure to absorb as much available testosterone as possible. Since cancers are constantly evolving new ways to fuel their growth, many of the recently approved therapies aim to block this process from different angles. For example, abiraterone blocks testosterone produced by the adrenal glands and the tumor cells themselves, and enzalutamide blocks the connection between proteins on the surface of prostate cancer cells and testosterone.
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How can genetic testing help to decide which patients will respond to therapies and which will not?
About 70 percent of men respond well to abiraterone and enzalutamide for an average of 12 to 18 months. The other 30 percent get no benefit from the drugs at all. I've been working with scientists in the Brady Urological Institute to test genetic markers that can predict which men may respond to these two drugs and which will not. Some 30 percent of men with advanced prostate cancer have an abnormal version of a prostate cancer protein that connects with testosterone. The protein is missing a key connector that binds to abiraterone and enzalutamide. The abnormal protein is caused by a genetic variant called AR-V7.
Most patients who test positive for AR-V7 get no benefit from abiraterone or enzalutamide. However, when men with the AR-V7 gene variant get chemotherapy, they can still benefit from this treatment. Men who do not have AR-V7 may respond very well to either enzalutamide, abiraterone or chemotherapies. This probably means that men with the AR-V7 genetic variant should receive chemotherapy sooner, while men who don't have the variant may respond well to hormonal drugs.
Who should get genomic sequencing on prostate cancer cells?
Comprehensive genetic profiling for prostate cancer is done only on a research basis at this time. Scientists have not found many genetic targets that can guide patients on which approved or experimental therapies may work for them at this time, but this is a very active area of investigation.