In a component of the phase III RADICALS-HD trial reported in The Lancet, Parker et al found that metastasis-free survival was improved with the addition of 24 months vs 6 months of androgen-deprivation therapy (ADT) to adjuvant radiotherapy in prostate cancer. A second component of the trial, not summarized here, has compared 6 months of ADT vs no ADT with postoperative radiotherapy in this setting.
Study Details
In the open-label trial, 1,523 patients from sites in Canada, Denmark, Ireland, and the United Kingdom were randomly assigned between January 2008 and July 2015 to receive 6 months of ADT (short-course ADT, n = 761) or 24 months of ADT (long-course ADT, n = 762) in addition to adjuvant radiotherapy following radical prostatectomy.
Radiotherapy was started at 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 gonadotropin releasing-hormone analog monthly in the short-course ADT group and every 3 months in the long-course ADT group (received by 84% of patients in each group), daily bicalutamide, or monthly degarelix. The primary outcome measure was metastasis-free survival in the intent-to-treat population.
Metastasis-Free Survival
With a median follow-up of 8.9 years (interquartile range = 7.0–10.0 years), metastasis-free survival events had occurred in 139 patients in the long-course group vs 174 in the short-course group (hazard ratio [HR] = 0.773, 95% confidence interval [CI] = 0.612–0.975, P = .029). Metastasis-free survival rate at 10 years was 78.1% (95% CI = 74.2%–81.5%) in the long-course group vs 71.9% (95% CI = 67.6%–75.7%) in the short-course group.
Overall survival events occurred in 100 patients in the long-course group vs 111 in the short-course group (HR = 0.880, 95% CI = 0.663–1.169, P = .38). Overall survival rate at 10 years was 84.6% (95% CI = 81.0%–87.5%) vs 82.0% (95% CI = 78.3%–85.2%).
KEY POINTS
- Metastasis-free survival was improved with 24 vs 6 months of ADT plus adjuvant radiotherapy.
- Metastasis-free survival at 10 years was 1% vs 71.9%.
Adverse Events
Adverse events of grade 1 to 4 occurred in 75% of the long-course group vs 71% of the short-term group, with no grade 5 events reported. Grade 3 to 4 adverse events occurred in 19% vs 14% of patients (P = .025), most commonly urethral stricture (10% vs 8%) and hematuria (7% vs 5%). Serious adverse events occurred in 49 patients in the long-term group, considered related to treatment in 13, and in 24 patents in the short-term group, considered related to treatment in 5.
The investigators concluded: “Compared with adding 6 months of ADT, adding 24 months of ADT improved metastasis-free survival in people receiving postoperative radiotherapy. For individuals who can accept the additional duration of adverse effects, long-course ADT should be offered with postoperative radiotherapy.”
Matthew R. Sydes, MSc, of the MRC Clinical Trials Unit at UCL, University College London, is the corresponding author of 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.
