Reconsidering Long-Term Hormone Therapy for Men with Low PSAs
A recent analysis calls into question the use of long-term hormone therapy for men with recurrent cancer and low PSA levels after prostate surgery.
For men with recurrent prostate cancer after having radical prostatectomies, the latest standard of care usually involves combining radiation treatment and hormone therapy to control or stop the spread of the disease. This standard of care became recommended practice two years ago after results from a randomized phase III clinical trial that showed adding two years of anti-androgen therapy to post-surgery radiation increased long-term overall survival rates for patients with recurring cancer. The study was the NRG Oncology/RTOG 9601.
However, a new analysis of the data split patients in the study according to high and low post-operative PSA levels. When viewed this way, patients with low PSAs after surgery did not see any overall survival benefit from hormone therapy. These patients also had a greatly increased risk of dying from other causes.
Study author Daniel Spratt, M.D., of the Genitourinary Clinical Research Program at the University of Michigan Rogel Cancer Center, said, “We found that the lower the PSA, the more harm the patient experienced. The higher the PSA, the more likely the patient was to benefit from hormone therapy because it decreased their chances of dying from prostate cancer and resulted in improved overall survival rates.”
The study included data on 760 patients who had recurrent cancer after prostate surgery. The patients were randomized to receive either just radiation, or radiation plus hormone therapy, specifically the anti-androgen bicalutamide.
The new analysis examined survival rates for patients with PSA levels higher or lower than 1.5 ng/mL after surgery.
For patients whose PSA was greater than 1.5 ng/mL, the new analysis found similar results to the original findings: adding long-term hormone therapy to radiation treatment improved survival by 55%. However, for men with PSA levels below 1.5 ng/mL after surgery, there was no survival benefit for adding long-term hormone therapy to radiation.
For patients with post-operative PSAs less than 0.6 ng/mL, the data was even more significant. Patients in this group who underwent the combined treatment of radiation and long-term hormone therapy were twice as likely to die from other causes. These patients were also three to four times more likely to have severe cardiac events and neurological problems. Although these side effects have been reported in the past, this is the first clinical trial to demonstrate them to this extent.
Dr. Spratt believes that the data calls into question the current clinical guidelines. “For post-operative patients with low PSAs, they do very well with just radiation therapy after surgery. They actually have very good long-term outcomes,” he said.
The findings were presented at the 61st Annual Meeting of the American Society for Radiation Oncology (ASTRO) in Chicago in September.
Dr. Catalona’s Response: Beware of Bicalutamide’s Side Effects
In this study, the form of hormonal therapy used (largely bicalutamide) can be associated with fluid retention, increased risk for blood clots, and other cardiovascular complications when used continuously in high doses. Also, bicalutamide therapy initially blocks the stimulation of prostate cancer cell growth by male hormones, but after a while, the cancer cells can mutate in such a way that bicalutamide might actually have the opposite effect and stimulate the growth of the cancer cells. Thus, the lower survival results of hormonal therapy reported might be due to the negative side effects of bicalutamide that may not occur with other forms of hormonal therapy.