September 28, 2005
Failure of PSA levels to fall in prostate cancer patients may lead to poor outcomes
Anthony D'Amico, MD, PhD
Despite great improvements in medicine's ability to detect and treat prostate cancer, many men still die of the disease after undergoing treatment. To address this ongoing challenge, researchers from Brigham and Women's Hospital (BWH) and Dana-Farber examined a diagnostic tool that had not previously been studied — prostate-specific antigen (PSA) nadir — the lowest PSA level achieved after treatment for prostate cancer. (PSA is a protein whose levels may indicate the presence of prostate cancer.)
Among men whose disease relapsed after radiation therapy or surgery, and who subsequently received hormonal treatments, researchers found that those whose PSA did not drop to an undetectable level (less than 0.2 nanograms per milliliter) had a much poorer outcome than those whose levels did drop. The research was published in the Sept. 20 issue of the Journal of Clinical Oncology.
According to lead author Alexandra Stewart, MD, formerly of BWH and Dana-Farber and currently with the Royal Marsden Hospital in England, "Many men with relapsed prostate cancer will still have a median survival of more than a decade after being given hormonal treatment. Some men, however, will have shorter survival if their PSA does not drop below 0.2 ng/mL. This indicates that PSA nadir could be used as an additional diagnostic tool to help determine the success of treatment. If PSA nadir failure is detected earlier, it could prompt physicians to more aggressively treat the disease."
Researchers studied 747 men, ages 45 to 88 years, who were followed for up to 9.5 years. These men underwent androgen suppression therapy (AST) after they experienced rising PSA levels despite having had surgery or radiation therapy. Of the 28 observed prostate cancer deaths in this group, 21 of them, or 75 percent, occurred in men whose PSA nadir was more than 0.2 ng/mL and who had a PSA doubling time of less than three months (a known indicator of aggressive disease). Patients whose PSA nadir was more than 0.2 ng/mL experienced a 20-fold increase in death from the disease.
According to the researchers, this indicates that PSA levels after treatment could be an indicator of prostate cancer-specific mortality and may require more aggressive treatment including chemotherapy, specifically Docetaxel. Recent research has indicated that Docetaxel can help reduce disease among men with very advanced prostate cancer.
According to study author Anthony D'Amico, MD, PhD, chief of Genitourinary Radiation Oncology at BWH and Dana-Farber, "These findings could also represent a new endpoint to be used in prostate cancer clinical trials. If a new endpoint were available that were a surrogate for survival, then it would be known whether a new drug has a beneficial effect much earlier."
Prostate cancer is the second most common cancer in men and the cause of approximately 30,000 deaths each year in the United States. Currently, PSA testing — a simple blood test performed during a routine visit with a primary care physician — helps provide evidence that the disease is present and also indicates how aggressive it is.
