Prostate cancer is the most common cancer in men and the second leading cause of death due to cancer in men. As many as 20 to 30 percent of men see their prostate-specific antigen (PSA) levels rise again at some point after surgery or radiation treatment for prostate cancer, a signal of the unrecognized spread of cancer beyond the prostate at diagnosis, inadequate surgery, or resistance to radiation and/or androgen deprivation therapy. These men are told that they have advanced cancer, and that they must now, with the counsel of their doctors, decide what to do about it.
When further treatment is later deemed necessary because the cancer has spread to bone or other body sites, withdrawal of androgens such as testosterone, which fuels cancer growth, is the standard of care for metastatic prostate cancer.
Although this androgen deprivation therapy, or ADT, can result in long-term remissions of metastatic prostate cancer, it is not curative. Cancer soon becomes resistant to this therapy and continues to advance. More than 50,000 American men have castration-resistant cancer, or cancer that no longer responds to ADT. It’s now believed that this cancer thrives because the cancer cells manufacture their own androgens.
Scientists are searching for alternate methods to block abnormal cell growth. Taxotere, approved by the FDA in 2004, was until recently the only therapy available for castration-resistant prostate cancer. In the past two years, however, five new drugs have been approved for advanced prostate cancer: sipuleucel-T, denosumab, abiraterone, cabazitaxel, and enzalutamide. A sixth, radium-223 dichloride, is expected to be approved later this year.
Significant progress has been made in treating advanced prostate cancer, not so much because survival is improved to a great extent, but rather because these new medications are proving that innovative approaches to treatment can be successful in halting the progress of this disease.
The FDA approved abiraterone in 2011. So successful was this drug in Phase III testing that the monitoring committee recommended unblinding the placebo-controlled group and having the patients switch to abiraterone.
Abiraterone blocks CYP17, a key driver of testosterone production and it caused 90 percent of patients in the clinical trial to have a dramatic reduction in PSA levels even though they had already taken anti-hormone drugs. Most patients who use abiraterone also have significant shrinkage of tumors and for those with bone pain due to metastases, many have improvement in pain levels.
Enzalutamide, approved in 2012, is the strongest inhibitor of testosterone receptors now available. The drug blocks testosterone receptors at three separate points, preventing testosterone from traveling into the nucleus of a cell and stimulating the genes that cause prostate cancer growth.
About 90 percent of men with advanced prostate cancer have bone metastases, a major cause of pain, disability, and eventual death. Radium-223 dichloride, an injectable form of radiation therapy, targets new bone growth caused by bone metastases and their tumor cells. The radiation kills these cells while avoiding damage to healthy cells.
Many in the prostate cancer research community now believe that these drugs, and others coming from the prostate cancer therapeutic pipeline, will one day help make advanced prostate cancer a chronic disease that’s successfully managed with a routine of daily medication, lifestyle modification, and regular checkups.
Where Are They Now
Radium-223 Dichloride was approved in 2013 for treatment of advanced prostate cancer, and all of these novel treatments are still the best and only options available to these patients. To date there are approximately 25 drugs approved for the treatment of prostate cancer, while many clinical trials for other prostate cancer drugs are ongoing. In 2016, scientists created a blood test able to check for a mutation indicating a poor response to these new prostate cancer drugs. Several versions of this technology have been released and clinically validated since its discovery. The blood tests developed to monitor this drug response are slated to be commercially available in 2017.