Adding antiandrogen therapy to radiation in patients with prostate cancer recurrence after radical prostatectomy improves long-term overall survival compared with radiation therapy alone, according to results of a new study (Shipley WU, et al. N Engl J Med. 2017;376:417-428).
“Surgery is a very common treatment for men with localized prostate cancer, but more than 30 percent of them will have recurrent disease; so we specialists in genitourinary oncology have been working to address this problem for a long time,” said lead investigator William U. Shipley, MD, FACR, Department of Radiation Oncology, Massachusetts General Hospital, in a February 1, 2017, press release issued by the hospital.
“This study’s findings—that adding antiandrogen therapy to the radiation typically used against recurrence reduces the incidence of metastasis, death from prostate cancer and overall deaths—will change the standard of care for patients experiencing a postoperative recurrence,” Dr Shipley added.
This double-blind, placebo-controlled clinical trial was sponsored by the National Cancer Institute and enrolled 760 patients with prostate cancer from 150 US sites between 1998 and 2003. Patients who had radical prostatectomy and had disease recurrence, as evidenced by a prostate-specific antigen (PSA) level between 0.2 ng/mL and 4.0 ng/mL, were included in the study (baseline median PSA level, 0.6 ng/mL).
Patients were randomized to antiandrogen therapy with bicalutamide (150 mg daily) or placebo for 24 months, in addition to 6.5 weeks of radiation therapy. Bicalutamide was selected because it was the most common antiandrogen therapy at the time of the study. Patients were evaluated at the beginning and end of radiation therapy, and at different intervals. The median follow-up was 13 years. The primary end point was overall survival.
An interim analysis in 2010 showed that treatment with bicalutamide plus radiation therapy was associated with lower rates of disease recurrence or metastasis than radiation alone. However, the researchers decided that longer follow-up was needed, because of the slow rate of progression of prostate cancer.
At an average of 12 years of follow-up, 5.8% of patients in the bicalutamide group died from prostate cancer compared with 13.4% of patients in the placebo group. The rate of distant metastases was 14.5% with bicalutamide and 23% with placebo.
The overall survival rate was 76.3% in the bicalutamide group versus 71.3% in the placebo group. A multivariate analysis demonstrated that the variables predicting higher rates of overall survival included bicalutamide therapy, a lower PSA level at the study entry, and age <65 years. No significant differences in long-term adverse effects were found between the treatment groups.
Overall, adding antiandrogen therapy to radiation increased long-term overall survival for this patient population and had significantly lower rates of disease-specific death, distant metastases, and disease recurrence than with radiation therapy alone.
Ongoing Clinical Trials
Since the start of the clinical trial in 1998, gonadotropin-releasing hormone (GnRH) agonist drugs have replaced bicalutamide in the treatment of patients with prostate cancer. Dr Shipley and colleagues noted that ongoing 2 major clinical trials—the RADICAL-HD study in the United Kingdom and the GETUG-16 study in France—are investigating the use of GnRH agonist drugs plus radiation therapy in a similar patient population.
The results of these studies “may provide additional insights as these data mature,” stated Dr Shipley and colleagues.
“Those trials started about five years ago, so it will take some time to get their results. But since both approaches act by lowering the supply of testosterone to the tumor itself, there isn’t any reason to expect the results to be different,” said Dr Shipley in the press release.