The optimal timing of radiotherapy after radical prostatectomy for prostate cancer is uncertain. We aimed to compare the efficacy and safety of adjuvant radiotherapy versus an observation policy with salvage radiotherapy for prostate-specific antigen (PSA) biochemical progression.
We did a randomised controlled trial enrolling patients with at least one risk factor (pathological T-stage 3 or 4, Gleason score of 7-10, positive margins, or preoperative PSA ≥10 ng/mL) for biochemical progression after radical prostatectomy (RADICALS-RT). The study took place in trial-accredited centres in Canada, Denmark, Ireland, and the UK. Patients were randomly assigned in a 1:1 ratio to adjuvant radiotherapy or an observation policy with salvage radiotherapy for PSA biochemical progression (PSA ≥0·1 ng/mL or three consecutive rises). Masking was not deemed feasible. Stratification factors were Gleason score, margin status, planned radiotherapy schedule (52·5 Gy in 20 fractions or 66 Gy in 33 fractions), and centre. The primary outcome measure was freedom from distant metastases, designed with 80% power to detect an improvement from 90% with salvage radiotherapy (control) to 95% at 10 years with adjuvant radiotherapy. We report on biochemical progression-free survival, freedom from non-protocol hormone therapy, safety, and patient-reported outcomes. Standard survival analysis methods were used. A hazard ratio (HR) of less than 1 favoured adjuvant radiotherapy. This study is registered with ClinicalTrials.gov, NCT00541047.
Between Nov 22, 2007, and Dec 30, 2016, 1396 patients were randomly assigned, 699 (50%) to salvage radiotherapy and 697 (50%) to adjuvant radiotherapy. Allocated groups were balanced with a median age of 65 years (IQR 60-68). Median follow-up was 4·9 years (IQR 3·0-6·1). 649 (93%) of 697 participants in the adjuvant radiotherapy group reported radiotherapy within 6 months; 228 (33%) of 699 in the salvage radiotherapy group reported radiotherapy within 8 years after randomisation. With 169 events, 5-year biochemical progression-free survival was 85% for those in the adjuvant radiotherapy group and 88% for those in the salvage radiotherapy group (HR 1·10, 95% CI 0·81-1·49; p=0·56). Freedom from non-protocol hormone therapy at 5 years was 93% for those in the adjuvant radiotherapy group versus 92% for those in the salvage radiotherapy group (HR 0·88, 95% CI 0·58-1·33; p=0·53). Self-reported urinary incontinence was worse at 1 year for those in the adjuvant radiotherapy group (mean score 4·8 vs 4·0; p=0·0023). Grade 3-4 urethral stricture within 2 years was reported in 6% of individuals in the adjuvant radiotherapy group versus 4% in the salvage radiotherapy group (p=0·020).
These initial results do not support routine administration of adjuvant radiotherapy after radical prostatectomy. Adjuvant radiotherapy increases the risk of urinary morbidity. An observation policy with salvage radiotherapy for PSA biochemical progression should be the current standard after radical prostatectomy.
Cancer Research UK, MRC Clinical Trials Unit, and Canadian Cancer Society.
Lancet (London, England). 2020 Sep 28 [Epub]
Christopher C Parker, Noel W Clarke, Adrian D Cook, Howard G Kynaston, Peter Meidahl Petersen, Charles Catton, William Cross, John Logue, Wendy Parulekar, Heather Payne, Rajendra Persad, Holly Pickering, Fred Saad, Juliette Anderson, Amit Bahl, David Bottomley, Klaus Brasso, Rohit Chahal, Peter W Cooke, Ben Eddy, Stephanie Gibbs, Chee Goh, Sandeep Gujral, Catherine Heath, Alastair Henderson, Ramasamy Jaganathan, Henrik Jakobsen, Nicholas D James, Subramanian Kanaga Sundaram, Kathryn Lees, Jason Lester, Henriette Lindberg, Julian Money-Kyrle, Stephen Morris, Joe O'Sullivan, Peter Ostler, Lisa Owen, Prashant Patel, Alvan Pope, Richard Popert, Rakesh Raman, Martin Andreas Røder, Ian Sayers, Matthew Simms, Jim Wilson, Anjali Zarkar, Mahesh K B Parmar, Matthew R Sydes
Department of Oncology, Royal Marsden NHS Foundation Trust, Sutton, UK; Institute of Cancer Research, Sutton, UK., Department of Oncology, Genito-Urinary Cancer Research Group, The Christie Hospital, Manchester, UK; Department of Surgery, The Christie Hospital, Manchester, UK; Department of Urology, Salford Royal Hospitals, Manchester, UK., MRC Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, UCL, London, UK., Department of Urology, Cardiff University School of Medicine, Cardiff University, Cardiff, UK., Department of Oncology, Copenhagen Prostate Cancer Center, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark., Department of Radiation Oncology, Princess Margaret Hospital, University Health Network, Toronto, ON, Canada., Department Of Urology, St James's University Hospital, Leeds, UK., Department of Oncology, The Christie Hospital, Manchester, UK., Department of Oncology, Canadian Cancer Trials Group, Queen's University, Kingston, ON, Canada., Department of Oncology, University College London Hospitals, London, UK., Department of Urology, Bristol Urological Institute, North Bristol Hospitals, Bristol, UK., Department of Urology, Centre Hospitalier de l'Université de Montreal, Montreal, QC, Canada., Department of Oncology, Mid Yorkshire Hospitals NHS Trust, Wakefield, UK., Department of Oncology, Bristol Cancer Institute, University Hospitals Bristol, Bristol, UK., St James's Institute of Oncology, Leeds, UK., Department of Urology, Copenhagen Prostate Cancer Center, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark., Department of Urology, Bradford Teaching Hospitals NHS Foundation Trust, Bradford, UK., Department of Urology, The Royal Wolverhampton NHS Trust, Wolverhampton, UK., Department of Urology, East Kent Hospitals University Foundation Trust, Canterbury, UK., Department of Oncology, Barking, Havering and Redbridge University Hospitals NHS Trust, Romford, UK., Department of Oncology, Royal Surrey County Hospital NHS Foundation Trust, Guildford, UK., Department of Urology, Barking, Havering and Redbridge University Hospitals NHS Trust, Romford, UK., Department of Clinical Oncology, University Hospital Southampton, Southampton, UK., Department of Urology, Maidstone and Tunbridge Wells NHS Trust, Maidstone, UK., Department of Urology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK., Department of Urology, Herlev University Hospital, Herlev, Denmark., Institute of Cancer Research, London, UK; Department of Oncology, Royal Marsden NHS Foundation Trust, London, UK., Department of Urology, Mid Yorkshire Hospitals NHS Trust, Wakefield, UK., Kent Oncology Centre, Maidstone Hospital, Kent, UK., Department of Oncology, South West Wales Cancer Centre, Swansea, UK., Department of Oncology, Herlev University Hospital, Herlev, Denmark., Department of Clinical Oncology, Guys Hospital, London, UK., Department of Clinical Oncology, Belfast Health and Social Care Trust, Belfast, UK., Mount Vernon Cancer Centre, Northwood, UK., Department of Oncology, Leeds Cancer Centre, St James's University Hospital, Leeds, UK., Department of Urology, Hillingdon Hospital, Middlesex, UK; Mount Vernon Hospital, Northwood, UK; Mount Vernon Cancer Centre, Northwood, UK., Department of Urology, Guys Hospital, London, UK., Department of Clinical Oncology, Kent Oncology Centre, Canterbury, UK., Department of Oncology, The Royal Wolverhampton NHS Trust, Wolverhampton, UK., Department of Urology, Hull University Hospitals NHS Trust, Hull, UK., Department of Urology, Anuerin Bevan University Health Board, Newport, UK., Department of Oncology, University Hospital Birmingham, Birmingham, UK., MRC Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, UCL, London, UK. Electronic address: .