Previous evidence indicates that adjuvant, short-course androgen deprivation therapy (ADT) improves metastasis-free survival when given with primary radiotherapy for intermediate-risk and high-risk localised prostate cancer. However, the value of ADT with postoperative radiotherapy after radical prostatectomy is unclear.
RADICALS-HD was an international randomised controlled trial to test the efficacy of ADT used in combination with postoperative radiotherapy for prostate cancer. Key eligibility criteria were indication for radiotherapy after radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to radiotherapy alone (no ADT) or radiotherapy with 6 months of ADT (short-course ADT), using monthly subcutaneous gonadotropin-releasing hormone analogue injections, daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as distant metastasis arising from prostate cancer or death from any cause. Standard survival analysis methods were used, accounting for randomisation stratification factors. The trial had 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 80% to 86% (hazard ratio [HR] 0·67). Analyses followed the intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov, NCT00541047.
Between Nov 22, 2007, and June 29, 2015, 1480 patients (median age 66 years [IQR 61-69]) were randomly assigned to receive no ADT (n=737) or short-course ADT (n=743) in addition to postoperative radiotherapy at 121 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 9·0 years (IQR 7·1-10·1), metastasis-free survival events were reported for 268 participants (142 in the no ADT group and 126 in the short-course ADT group; HR 0·886 [95% CI 0·688-1·140], p=0·35). 10-year metastasis-free survival was 79·2% (95% CI 75·4-82·5) in the no ADT group and 80·4% (76·6-83·6) in the short-course ADT group. Toxicity of grade 3 or higher was reported for 121 (17%) of 737 participants in the no ADT group and 100 (14%) of 743 in the short-course ADT group (p=0·15), with no treatment-related deaths.
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.
Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society.
Lancet (London, England). 2024 May 16 [Epub ahead of print]
Chris C Parker, Noel W Clarke, Adrian D Cook, Howard Kynaston, Charles N Catton, William R Cross, Peter M Petersen, Rajendra A Persad, Fred Saad, Lorna C Bower, John Logue, Heather Payne, Silvia Forcat, Cindy Goldstein, Claire Murphy, Juliette Anderson, Maroie Barkati, David M Bottomley, Jennifer Branagan, Ananya Choudhury, Peter W M Chung, Lyn Cogley, Chee L Goh, Peter Hoskin, Vincent Khoo, Shawn C Malone, Lindsey Masters, Stephen L Morris, Abdenour Nabid, Aldrich D Ong, Rakesh Raman, Kathryn L Tarver, Alison C Tree, Jane Worlding, James P Wylie, Anjali M Zarkar, Wendy R Parulekar, Mahesh K B Parmar, Matthew R Sydes, RADICALS investigators
The Royal Marsden NHS Foundation Trust, London, UK; The Institute of Cancer Research, London, UK., Department of Urology, The Christie NHS Foundation Trust, Manchester, UK; Division of Cancer Sciences, University of Manchester, Manchester, UK; Department of Urology, Salford Royal Hospital, Salford, UK., MRC Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, University College London, London, UK., Division of Cancer and Genetics, Cardiff University Medical School, Cardiff, UK., Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada., Department of Urology, St James's University Hospital, Leeds, UK., Department of Oncology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark., Department of Urology, Bristol Urological Institute, Bristol, UK., Department of Urology, Centre Hospitalier de l'Université de Montréal, Montreal, QC, Canada., The Royal Marsden NHS Foundation Trust, London, UK; The Institute of Cancer Research, London, UK; Guy's and St Thomas' NHS Foundation Trust, London, UK., Department of Urology, The Christie NHS Foundation Trust, Manchester, UK., The Prostate Centre, London, UK., Department of Clinical Oncology, St James's University Hospital, Leeds, UK., Department of Radiation Oncology, Centre Hospitalier de l'Université de Montréal, Montreal, QC, Canada., Northampton General Hospital, Northampton, UK., Department of Urology, The Christie NHS Foundation Trust, Manchester, UK; Division of Cancer Sciences, University of Manchester, Manchester, UK., Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada; Department of Radiation Oncology, University of Toronto, Toronto, ON, Canada., Derriford Hospital, Plymouth, UK., Royal Surrey Hospital, Guildford, UK., Division of Cancer Sciences, University of Manchester, Manchester, UK; Mount Vernon Cancer Centre, Northwood, UK., The Ottawa Hospital, University of Ottawa, Ottawa, ON, Canada., Guy's and St Thomas' NHS Foundation Trust, London, UK., Service de Radio-Oncologie, Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, QC, Canada., Max Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada., Kent Oncology Centre, Kent and Canterbury Hospital, Canterbury, UK., Department of Oncology, Queen's Hospital, Romford, UK., University Hospitals Coventry and Warwickshire NHS Trust, Coventry, UK., Department of Oncology, University Hospitals Birmingham, Birmingham, UK., Canadian Cancer Trials Group, Queen's University, Kingston, ON, Canada., MRC Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, University College London, London, UK. Electronic address: .