Similar Outcomes with 18 Months versus 36 Months of Androgen Ablation Added to Radiation in High-Risk Prostate Cancer
Orlando, FL—Similar overall survival (OS) and disease-specific survival were achieved after 18 months of androgen ablation therapy compared with 36 months when combined with radiation therapy as primary therapy for patients with high-risk prostate cancer. A shorter course of androgen ablation has the potential to reduce unwanted side effects and to improve quality of life, and it may reduce the cost of prostate cancer therapy, according to the results of a phase 3 clinical trial reported at the 2013 Genitourinary Cancers Symposium.
“The side effects of hormonal therapy make the lives of most of our patients quite miserable,” said lead investigator Abdenour Nabid, MD, Associate Professor, Department of Radiation Oncology, Centre Hospitalier Universitaire de Sherbrooke, Quebec, Canada. These side effects include “castration syndrome” (ie, hot flashes, decreased sexual drive, impotence, and fatigue), musculoskeletal complaints, cardiovascular effects, and other problems.
The optimal duration of androgen ablation therapy for patients with high-risk prostate cancer is debatable. “A shorter course could reduce the quantity and intensity of its unpleasant side effects as well as treatment costs. We hope these results will convince doctors that they can stop hormone therapy after 1.5 years instead of 2 to 3 years,” Dr Nabid stated.
This study enrolled 630 patients with node-negative, high-risk prostate cancer (stage T3 or T4) who received radiotherapy to the pelvic area and to the prostate bed. Patients were randomized to 18 months of androgen ablation therapy (bicalutamide [Casodex] for 1 month plus goserelin [Zoladex] every 3 months) versus 36 months of androgen ablation therapy. Androgen ablation was started 4 months before radiation and was continued during and after radiation.
The patients (median age, 71 years) in the 2 arms had comparable demographic and disease characteristics, including the numbers of patients with a prostate-specific antigen >20 ng/mL and a Gleason score of >7. In both groups, 20% of the patients had Gleason scores of 9 and 10.
At a median follow-up of 77 months, the 2 groups had no significant difference in biochemical failure, metastasis, bone-only metastasis, and cause of death. Mortality rates were 22.9% (N = 71) in the 18-month hormone therapy arm and 23.8% (N = 76) in the 32-month arm. Of these 147 deaths, 116 were deemed unrelated to prostate cancer.
“Prolonging androgen ablation therapy will not prevent bone metastasis,” Dr Nabid stated.
The 5-year OS rates were 92.1% in the shorter-duration cohort versus 86.8% in the longer-duration cohort, and 10-year OS rates were 63.6% versus 63.2%, respectively. The 5-year disease-specific survival rate was 97.6% for the shorter-duration arm versus 96.4% for the longer-duration arm; the 10-year disease-specific survival rates were 87.2% in both arms.
The most frequent cause of death was a second cancer (7.3% of patients); 4.9% died of prostate cancer in both groups, and 4.4% died of cardiovascular disease in both groups.
“This study shows that 18 months of androgen ablation does the job. Treatment with 18 months of androgen blockade is safe in localized prostate cancer and could represent a threshold for no further gain,” Dr Nabid said.
Although the full peer-reviewed publication of the results, as well as longer follow-up, are needed to change the standard of care to 18 months, the investigators agreed that shortening the course of therapy to at least 24 months will prove to be