FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Adding antiandrogen treatment to salvage radiotherapy markedly improves long-term survival and disease-specific mortality, reduces the rate of distant metastases, and decreases the incidence of further recurrences in men who have an initial biochemical recurrence of prostate cancer, according to a report in the New England Journal of Medicine.
These are the long-term findings of a prospective multicenter trial begun in 1998, which compared standard radiotherapy plus daily oral bicalutamide against radiotherapy plus placebo. The survival benefit became evident only during the second decade after treatment, said William U. Shipley, MD, of Massachusetts General Hospital and Harvard Medical School, Boston, and his associates.
During the course of this study, bicalutamide was superseded by injectable GnRH agonists as the add-on antiandrogen treatment of choice, “but the hypothesis tested in this trial remains very relevant,” they noted. “Our trial presents proof of principle that the addition of hormone-based therapy to salvage radiation therapy is associated with significant and clinically important lower rates of prostate-cancer metastases and death.”
The study involved 760 men (median age, 65 years) who had undergone radical prostatectomy with lymphadenectomy for T2 or T3 prostate cancer without nodal involvement. A median of 2 years after surgery, all of them showed rising PSA levels (biochemical recurrence) but no metastases. They were randomly assigned in a double-blind fashion to receive salvage radiotherapy plus a 2-year course of bicalutamide (384 patients) or matching placebo (376 patients) and were followed for a median of 13 years.
The primary endpoint – the rate of overall survival at 12 years – was 76.3% in the bicalutamide group and 71.3% in the placebo group, for a hazard ratio of 0.77. An estimated 20 patients would need to be treated with bicalutamide to avoid one death over a 12-year period, the investigators said (N Engl J Med. 2017 Feb 2 [doi: 10.1056/NEJMoa1607529]).
The rates of prostate cancer–specific death were 5.8% and 13.4%, respectively (HR, 0.49). The cumulative incidences of distant metastases were 14.5% vs. 23.0% (HR, 0.63), and those of biochemical recurrence were 44.0% vs. 67.9% (HR, 0.48). Post hoc subgroup analyses showed that the survival benefit was greatest among men who had the most aggressive cancers, such as those with the highest PSA levels, the highest Gleason scores, and positive rather than negative surgical margins.
Compared with placebo, bicalutamide did not exacerbate early or late bladder, bowel, hematologic, or hepatic effects of radiotherapy, and it was not associated with any increase in cardiac death, Dr. Shipley and his associates said.
The National Cancer Institute and AstraZeneca supported the trial. Dr. Shipley reported previously holding stock in PFS Genomics; his associates reported ties to numerous industry sources.
