Abstract
Background: There is strong evidence that adjuvant, short-course androgen deprivation therapy (ADT) improves MFS when given with primary RT for intermediate and high-risk localised prostate cancer. However, there is uncertainty about the value of ADT with post-operative radiotherapy after radical prostatectomy which requires resolution.
Methods: RADICALS-HD was a randomised controlled trial. Key eligibility criteria were: indication for RT after radical prostatectomy for prostate cancer, PSA<5ng/ml, absence of metastatic disease and written consent. Participants were randomised to RT alone (“None”) or RT with 6 months ADT (“Short”), using either monthly subcutaneous GnRH Analogue injections or bicalutamide monotherapy 150mg daily. Randomisation was done centrally through minimisation with a random element balanced for prognostic variables. The allocated treatment was not concealed The primary outcome measure was metastasis-free survival (MFS) defined as distant metastasis arising from prostate cancer or death from any cause. The trial had >80% power with 2-sided alpha=5% to detect an absolute increase in 10-year MFS from 80% to 86% (HR=0.67). Analyses followed intention-to-treatment principles.
Results: Between 22nd November 2007 and 29th June 2015, 1480 patients were randomly allocated to None (n=737) or Short (n=743) from in 121 hospitals in 4 countries. With median follow-up of 9 years (IQR 7.1,10.1), MFS events had been reported for 268 patients (142 None, 126 Short): HR=0.886 (95%CI 0.688 to 1.140, p=0.346). At 10 years, 79.2% None and 80.4% Short were alive without metastatic disease. Grade 3+ toxicity was reported for 17% (121/737) None and 14% (100/743) Short (p=0.154) with no treatment-related deaths.
Interpretation: Metastatic disease is uncommon following post-operative bed radiotherapy after radical prostatectomy. Adding 6 months ADT to this radiotherapy did not improve MFS, but did delay time to salvage ADT. In our view, these data are not sufficient to recommend use of short-course ADT with post-operative radiotherapy in the type of patient this comparison recruited.
Methods: RADICALS-HD was a randomised controlled trial. Key eligibility criteria were: indication for RT after radical prostatectomy for prostate cancer, PSA<5ng/ml, absence of metastatic disease and written consent. Participants were randomised to RT alone (“None”) or RT with 6 months ADT (“Short”), using either monthly subcutaneous GnRH Analogue injections or bicalutamide monotherapy 150mg daily. Randomisation was done centrally through minimisation with a random element balanced for prognostic variables. The allocated treatment was not concealed The primary outcome measure was metastasis-free survival (MFS) defined as distant metastasis arising from prostate cancer or death from any cause. The trial had >80% power with 2-sided alpha=5% to detect an absolute increase in 10-year MFS from 80% to 86% (HR=0.67). Analyses followed intention-to-treatment principles.
Results: Between 22nd November 2007 and 29th June 2015, 1480 patients were randomly allocated to None (n=737) or Short (n=743) from in 121 hospitals in 4 countries. With median follow-up of 9 years (IQR 7.1,10.1), MFS events had been reported for 268 patients (142 None, 126 Short): HR=0.886 (95%CI 0.688 to 1.140, p=0.346). At 10 years, 79.2% None and 80.4% Short were alive without metastatic disease. Grade 3+ toxicity was reported for 17% (121/737) None and 14% (100/743) Short (p=0.154) with no treatment-related deaths.
Interpretation: Metastatic disease is uncommon following post-operative bed radiotherapy after radical prostatectomy. Adding 6 months ADT to this radiotherapy did not improve MFS, but did delay time to salvage ADT. In our view, these data are not sufficient to recommend use of short-course ADT with post-operative radiotherapy in the type of patient this comparison recruited.
| Original language | English |
|---|---|
| Journal | The Lancet |
| Publication status | Accepted/In press - 11 Apr 2024 |
