Final results of a phase 3 trial confirm the progression-free survival (PFS) benefit of adding short-term androgen suppression to radiotherapy as salvage treatment for men who experience rising PSA following radical prostatectomy for prostate cancer (PCa), investigators concluded in a paper published in Lancet Oncology.
In a post-hoc analysis of men in the GETUG-AFU 16 trial, the 120-month PFS rates were 64% for men treated with radiotherapy plus 6 months of androgen deprivation therapy with goserelin compared with 49% for those who received radiotherapy alone. The combined treatment was significantly associated with a 46% reduction in the risk of disease progression—the study’s primary end point—compared with radiotherapy alone. The investigators, led by Christian Carrie, MD, of Léon Bérard Center and the University of Lyon in France, defined PFS as the time from randomization to documented biologic recurrence or clinical progression (or both), death from any cause, or censoring at the date of last follow-up.
In addition, the investigators found that the combined treatment offered an advantage in terms of metastasis-free survival (MFS), a prespecified secondary end point of the trial. The 120-month MFS rates were 75% for the combined treatment arm compared with 69% for the radiotherapy alone arm. The combined treatment was significantly associated with a 27% decreased risk of metastasis compared with radiotherapy alone.
Overall survival rates at 120 months did not differ significantly between the combined treatment and radiotherapy alone arms (86% vs 85%), Dr Carrie’s team reported.
When adding androgen suppression to salvage radiotherapy, 14 patients would need to be treated to spare 1 patient from experiencing metastasis or death in the 10 years after salvage therapy, according to the investigators.
Subgroup analyses found that the beneficial effect of the combined treatment on PFS was significantly greater for patients with low-risk than high-risk cancer. Compared with radiotherapy alone, the combined treatment was significantly associated with a 53% decreased risk of progression in the low-risk patients compared with a 44% decreased risk in the high-risk group. The investigators found no significant difference in MFS between treatment arms when they stratified patients according to risk group.
“Our results confirm the benefit of adding short-term androgen deprivation therapy to salvage radiotherapy on metastasis-free survival in patients with biological recurrence after radical prostatectomy,” the authors wrote.
Dr Carrie and his colleagues noted that the FDA recently approved MFS as an end point for patients with PCa enrolled in clinical trials, and MFS “has been described as a strong surrogate of overall survival.”
The GETUG-AFU 16 trial enrolled patients from October 19, 2006 to March 30, 2010. Dr Carrie and his collaborators randomly assigned 743 men with to receive radiotherapy alone (374 patients) or radiotherapy in addition to goserelin (369 patients). One patient in the radiotherapy alone group later withdrew consent, leaving 373 patients in that group. The median follow-up was 112 months. In the first analysis of the trial, which was published in 2016, only the first progression event was collected, so MFS could not be analyzed, the authors noted.
Carrie C, Magné N, Burban-Provost P, et al. Short-term androgen deprivation therapy combined with radiotherapy as salvage treatment after radical prostatectomy for prostate cancer (GETUG-AFU 16): a 112-mont follow-up of a phase 3, randomised trial [published online October 16, 2019]. Lancet Oncol. doi: 10.1016/S1470-2045(19)30486-3