The optimal timing of radiotherapy (RT) after radical prostatectomy for prostate cancer has been uncertain. RADICALS-RT compared efficacy and safety of adjuvant RT versus an observation policy with salvage RT for PSA failure.
RADICALS-RT was a randomised controlled trial enrolling patients with ≥1 risk factor (pT3/4, Gleason 7-10, positive margins, pre-op PSA≥10ng/ml) for recurrence after radical prostatectomy. Patients were randomised 1:1 to adjuvant RT ("Adjuvant-RT") or an observation policy with salvage RT for PSA failure ("Salvage-RT") defined as PSA≥0.1ng/ml or 3 consecutive rises. Stratification factors were Gleason score, margin status, planned RT schedule (52.5Gy/20 fractions or 66Gy/33 fractions) and treatment centre. The primary outcome measure was freedom-from-distant metastasis, designed with 80% power to detect an improvement from 90% with Salvage-RT (control) to 95% at 10yr with Adjuvant-RT. Secondary outcome measures were bPFS, freedom-from-non-protocol hormone therapy, safety and patient-reported outcomes. Standard survival analysis methods were used; HR<1 favours Adjuvant-RT.
Between Oct-2007 and Dec-2016, 1396 participants from UK, Denmark, Canada and Ireland were randomised: 699 Salvage-RT, 697 Adjuvant-RT. Allocated groups were balanced with median age 65yr. 93% (649/697) Adjuvant-RT reported RT within 6m after randomisation; 39% (270/699) Salvage-RT reported RT during follow-up. Median follow-up was 7.8 years. With 80 distant metastasis events, 10yr FFDM was 93% for Adjuvant-RT and 90% for Salvage-RT: HR=0.68 (95%CI 0·43-1·07, p=0·095). Of 109 deaths, 17 were due to prostate cancer. Overall survival was not improved (HR=0.980, 95%CI 0.667-1.440, p=0.917). Adjuvant-RT reported worse urinary and faecal incontinence one year after randomisation (p=0.001); faecal incontinence remained significant after ten years (p=0.017).
Long-term results from RADICALS-RT confirm adjuvant RT after radical prostatectomy increases the risk of urinary and bowel morbidity, but does not meaningfully improve disease control. An observation policy with salvage RT for PSA failure should be the current standard after radical prostatectomy.
Annals of oncology : official journal of the European Society for Medical Oncology. 2024 Apr 05 [Epub ahead of print]
C C Parker, P M Petersen, A D Cook, N W Clarke, C Catton, W R Cross, H Kynaston, W R Parulekar, R A Persad, F Saad, L Bower, G C Durkan, J Logue, C Maniatis, D Noor, H Payne, J Anderson, A K Bahl, F Bashir, D M Bottomley, K Brasso, L Capaldi, P W Cooke, C Chung, J Donohue, B Eddy, C M Heath, A Henderson, A Henry, R Jaganathan, H Jakobsen, N D James, J Joseph, K Lees, J Lester, H Lindberg, A Makar, S L Morris, N Oommen, P Ostler, L Owen, P Patel, A Pope, R Popert, R Raman, V Ramani, A Røder, I Sayers, M Simms, V Srinivasan, S Sundaram, K L Tarver, A Tran, P Wells, J Wilson, A M Zarkar, M K M Parmar, M R Sydes, RADICALS investigators
Institute of Cancer Research, Royal Marsden NHS Foundation Trust, Sutton, UK., Dept of Oncology, Copenhagen Prostate Cancer Center, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark., MRC Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, UCL, London, UK., Dept of Urology, The Christie and Salford Royal Hospitals, Manchester, UK; The University of Manchester, Manchester, UK., Dept of Radiation Oncology, Princess Margaret Hospital, University Health Network, Toronto, ON, Canada., Dept of Urology, St James's University Hospital, Leeds, UK., Division of Cancer and Genetics, Cardiff University, Cardiff, UK., Canadian Cancer Trials Group, Queen's University, Kingston, ON, Canada., Dept of Urology, Bristol Urological Institute, Bristol, UK., Dept of Urology, Centre Hospitalier de l'Université de Montréal, Montreal, Canada., Guy's and St Thomas' NHS Foundation Trust, London, UK; Institute of Cancer Research, Royal Marsden NHS Foundation Trust, London, UK., Dept of Urology, University Hospital Galway, Galway, Ireland., Dept of Oncology, The Christie Hospital NHS FT, Wilmslow Road, Manchester, UK., The Prostate Centre, London, UK., St James's Institute of Oncology, Leeds, UK., Bristol Haematology and Oncology Centre, University Hospitals Bristol & Weston NHS Trust, Bristol, UK., Queen's Centre for Oncology, Castle Hill Hospital, Hull University Teaching Hospitals NHS Trust, Cottingham, UK., Dept of Urology, Copenhagen Prostate Cancer Center, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark; Dept of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark., Worcester Oncology Centre, Worcestershire Acute NHS Hospitals Trust, Worcester, UK., Dept of Urology, The Royal Wolverhampton NHS Trust, Wolverhampton, UK., Dept of Urology, Maidstone and Tunbridge Wells NHS Trust, Maidstone, UK., East Kent University Hospitals Foundation Trust, Kent, UK., Dept of Clinical Oncology, University Hospital Southampton NHS Foundation Trust, Southampton, UK., Leeds Institute of Medical Research, University of Leeds, Leeds, UK., Dept of Urology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK., Dept of Urology, Herlev University Hospital, Herlev, Denmark., Institute of Cancer Research, Royal Marsden NHS Foundation Trust, London, UK., Leeds Teaching Hospitals, UK; York and Scarborough Teaching Hospitals, UK., Dept of Oncology, Maidstone and Tunbridge Wells NHS Trust, Maidstone, UK., South West Wales Cancer Centre, Singleton Hospital, Swansea, UK., Dept of Oncology, Herlev University Hospital, Herlev, Denmark., Dept of Urology, Worcestershire Acute Hospitals Trust, Worcester, UK., Guy's and St Thomas' NHS Foundation Trust, London, UK., Wrexham Maelor Hospital, Wrexham, UK., Mount Vernon Cancer Centre, Northwood, UK., Bradford Royal Infirmary, Bradford, UK; Leeds Cancer Centre, Leeds, UK., Dept of Urology, University College London Hospitals, London, UK., Kent Oncology Centre, Kent & Canterbury Hospital, Canterbury, UK., Dept of Urology, The Christie and Salford Royal Hospitals, Manchester, UK., Dept of Urology, Copenhagen Prostate Cancer Center, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark., Deanesly Centre, New Cross Hospital, Wolverhampton, UK., Dept of Urology, Hull University Hospitals NHS Trust, UK., Glan Clwyd Hospital, Betsi Cadwaladr University Health Board, Rhyl, UK., Dept of Urology, Mid Yorkshire Teaching Hospital, Pontefract, UK., Dept of Oncology, Queen's Hospital, Romford, UK., St Bartholomews Hospital, London UK., Royal Gwent Hospital, Newport, UK., Dept of Oncology, University Hospitals Birmingham, Birmingham, UK., MRC Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, UCL, London, UK. Electronic address: .