In a component of the phase III RADICALS-HD trial reported in The Lancet, Chris C. Parker, MD, and colleagues found that metastasis-free survival was not significantly improved with 6 months of androgen-deprivation therapy (ADT) vs no ADT together with adjuvant radiotherapy in patients with prostate cancer.
Chris C. Parker, MD
A second component of the trial, summarized here, compared 24 months vs 6 months of ADT with postoperative radiotherapy in this setting.
Study Details
In the open-label RADICALS-HD trial, 1,480 patients from sites in Canada, Denmark, Ireland, and the United Kingdom were randomly assigned between November 2007 and June 2015 to receive 6 months of ADT (short-course ADT, n = 743) or no ADT (n = 737) in addition to adjuvant radiotherapy following radical prostatectomy. Radiotherapy was started approximately 2 months after the start of hormone treatment, with schedules of either 52.5 Gy in 20 fractions over 4 weeks or 66.0 Gy in 33 fractions over 6.5 weeks. ADT consisted of monthly gonadotropin-releasing hormone analogue injections (received by 83%–84% of patients in each group), daily bicalutamide, or monthly subcutaneous degarelix.
The primary outcome measure of the study was metastasis-free survival in the intent-to-treat population.
Metastasis-Free Survival
With a median follow-up of 9.0 years (interquartile range = 7.1–10.1 years), metastasis-free survival events were reported in 126 patients in the short-course ADT group vs 142 in the no-ADT group (hazard ratio [HR] = 0.886, 95% confidence interval [CI] = 0.688–1.140, P = .35). Metastasis-free survival at 10 years was 80.4% (95% CI = 76.6%–83.6%) vs 79.2% (95% CI = 75.4%–82.5%), respectively.
Overall survival events occurred in 92 patients in the short-course ADT group vs 98 in the no-ADT group (HR = 0.882, 95% CI = 0.651–1.194, P = .42). Overall survival at 10 years was 85.3% (95% CI = 81.7%–88.3%) in the short-course ADT group vs 85.6% (95% CI = 82.2%–88.4%) in the no-ADT group.
KEY POINTS
- Metastasis-free survival was not significantly improved with 6 months of ADT v no ADT plus adjuvant radiotherapy.
- Metastasis-free survival at 10 years was 80.4% vs 79.2%.
Adverse Events
Grade ≥ 3 adverse events occurred in 14% of patients in the short-course group vs 17% of those in the no-ADT group (P = .15), most commonly urethral stricture (7% vs 7%) and hematuria (4% vs 7%). Serious adverse events occurred in 7 vs 11 patients. No treatment-related deaths were reported.
The investigators concluded, “Metastatic disease is uncommon following postoperative bed radiotherapy after radical prostatectomy. Adding 6 months of ADT to this radiotherapy did not improve metastasis-free survival compared with no ADT. These findings do not support the use of short-course ADT with postoperative radiotherapy in this patient population.”
Matthew R. Sydes, MSc, of the MRC Clinical Trials Unit at UCL, University College London, is the corresponding author for The Lancet article.
Disclosure: The study was funded by Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and the Canadian Cancer Society. For full disclosures of the study authors, visit thelancet.com.
