Christopher C Parker1, Noel W Clarke2, Adrian D Cook3, Howard G Kynaston4, Peter Meidahl Petersen5, Charles Catton6, William Cross7, John Logue8, Wendy Parulekar9, Heather Payne10, Rajendra Persad11, Holly Pickering3, Fred Saad12, Juliette Anderson13, Amit Bahl14, David Bottomley15, Klaus Brasso16, Rohit Chahal17, Peter W Cooke18, Ben Eddy19, Stephanie Gibbs20, Chee Goh21, Sandeep Gujral22, Catherine Heath23, Alastair Henderson24, Ramasamy Jaganathan25, Henrik Jakobsen26, Nicholas D James27, Subramanian Kanaga Sundaram28, Kathryn Lees29, Jason Lester30, Henriette Lindberg31, Julian Money-Kyrle21, Stephen Morris32, Joe O'Sullivan33, Peter Ostler34, Lisa Owen35, Prashant Patel25, Alvan Pope36, Richard Popert37, Rakesh Raman38, Martin Andreas Røder16, Ian Sayers39, Matthew Simms40, Jim Wilson41, Anjali Zarkar42, Mahesh K B Parmar3, Matthew R Sydes43. 1. Department of Oncology, Royal Marsden NHS Foundation Trust, Sutton, UK; Institute of Cancer Research, Sutton, UK. 2. 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. 3. MRC Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, UCL, London, UK. 4. Department of Urology, Cardiff University School of Medicine, Cardiff University, Cardiff, UK. 5. Department of Oncology, Copenhagen Prostate Cancer Center, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark. 6. Department of Radiation Oncology, Princess Margaret Hospital, University Health Network, Toronto, ON, Canada. 7. Department Of Urology, St James's University Hospital, Leeds, UK. 8. Department of Oncology, The Christie Hospital, Manchester, UK. 9. Department of Oncology, Canadian Cancer Trials Group, Queen's University, Kingston, ON, Canada. 10. Department of Oncology, University College London Hospitals, London, UK. 11. Department of Urology, Bristol Urological Institute, North Bristol Hospitals, Bristol, UK. 12. Department of Urology, Centre Hospitalier de l'Université de Montreal, Montreal, QC, Canada. 13. Department of Oncology, Mid Yorkshire Hospitals NHS Trust, Wakefield, UK. 14. Department of Oncology, Bristol Cancer Institute, University Hospitals Bristol, Bristol, UK. 15. St James's Institute of Oncology, Leeds, UK. 16. Department of Urology, Copenhagen Prostate Cancer Center, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark. 17. Department of Urology, Bradford Teaching Hospitals NHS Foundation Trust, Bradford, UK. 18. Department of Urology, The Royal Wolverhampton NHS Trust, Wolverhampton, UK. 19. Department of Urology, East Kent Hospitals University Foundation Trust, Canterbury, UK. 20. Department of Oncology, Barking, Havering and Redbridge University Hospitals NHS Trust, Romford, UK. 21. Department of Oncology, Royal Surrey County Hospital NHS Foundation Trust, Guildford, UK. 22. Department of Urology, Barking, Havering and Redbridge University Hospitals NHS Trust, Romford, UK. 23. Department of Clinical Oncology, University Hospital Southampton, Southampton, UK. 24. Department of Urology, Maidstone and Tunbridge Wells NHS Trust, Maidstone, UK. 25. Department of Urology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK. 26. Department of Urology, Herlev University Hospital, Herlev, Denmark. 27. Institute of Cancer Research, London, UK; Department of Oncology, Royal Marsden NHS Foundation Trust, London, UK. 28. Department of Urology, Mid Yorkshire Hospitals NHS Trust, Wakefield, UK. 29. Kent Oncology Centre, Maidstone Hospital, Kent, UK. 30. Department of Oncology, South West Wales Cancer Centre, Swansea, UK. 31. Department of Oncology, Herlev University Hospital, Herlev, Denmark. 32. Department of Clinical Oncology, Guys Hospital, London, UK. 33. Department of Clinical Oncology, Belfast Health and Social Care Trust, Belfast, UK. 34. Mount Vernon Cancer Centre, Northwood, UK. 35. Department of Oncology, Leeds Cancer Centre, St James's University Hospital, Leeds, UK. 36. Department of Urology, Hillingdon Hospital, Middlesex, UK; Mount Vernon Hospital, Northwood, UK; Mount Vernon Cancer Centre, Northwood, UK. 37. Department of Urology, Guys Hospital, London, UK. 38. Department of Clinical Oncology, Kent Oncology Centre, Canterbury, UK. 39. Department of Oncology, The Royal Wolverhampton NHS Trust, Wolverhampton, UK. 40. Department of Urology, Hull University Hospitals NHS Trust, Hull, UK. 41. Department of Urology, Anuerin Bevan University Health Board, Newport, UK. 42. Department of Oncology, University Hospital Birmingham, Birmingham, UK. 43. MRC Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, UCL, London, UK. Electronic address: m.sydes@ucl.ac.uk.
Abstract
BACKGROUND: 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. METHODS: 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. FINDINGS: 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). INTERPRETATION: 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. FUNDING: Cancer Research UK, MRC Clinical Trials Unit, and Canadian Cancer Society.
BACKGROUND: 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. METHODS: 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. FINDINGS: 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). INTERPRETATION: 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. FUNDING: Cancer Research UK, MRC Clinical Trials Unit, and Canadian Cancer Society.
Authors: Philip Sutera; Matthew P Deek; Kim Van der Eecken; Alexander W Wyatt; Amar U Kishan; Jason K Molitoris; Matthew J Ferris; M Minhaj Siddiqui; Zaker Rana; Mark V Mishra; Young Kwok; Elai Davicioni; Daniel E Spratt; Piet Ost; Felix Y Feng; Phuoc T Tran Journal: Prostate Date: 2022-08 Impact factor: 4.012
Authors: Ashesh B Jani; Eduard Schreibmann; Subir Goyal; Raghuveer Halkar; Bruce Hershatter; Peter J Rossi; Joseph W Shelton; Pretesh R Patel; Karen M Xu; Mark Goodman; Viraj A Master; Shreyas S Joshi; Omer Kucuk; Bradley C Carthon; Mehmet A Bilen; Olayinka A Abiodun-Ojo; Akinyemi A Akintayo; Vishal R Dhere; David M Schuster Journal: Lancet Date: 2021-05-07 Impact factor: 79.321
Authors: Michael J Morris; Jose Mauricio Mota; Kristine Lacuna; Patrick Hilden; Martin Gleave; Michael A Carducci; Fred Saad; Erica D Cohn; Julie Filipenko; Glenn Heller; Neal Shore; Andrew J Armstrong; Howard I Scher Journal: Eur Urol Oncol Date: 2021-05-18
Authors: Spyridon P Basourakos; Michael Tzeng; Patrick J Lewicki; Krishnan Patel; Bashir Al Hussein Al Awamlh; Siv Venkat; Jonathan E Shoag; Michael A Gorin; Christopher E Barbieri; Jim C Hu Journal: Front Oncol Date: 2021-05-28 Impact factor: 6.244
Authors: Fabio Zattoni; Isabel Heidegger; Veeru Kasivisvanathan; Alexander Kretschmer; Giancarlo Marra; Alessandro Magli; Felix Preisser; Derya Tilki; Igor Tsaur; Massimo Valerio; Roderick van den Bergh; Claudia Kesch; Francesco Ceci; Christian Fankhauser; Giorgio Gandaglia Journal: Front Surg Date: 2021-07-09
Authors: Shawn Dason; Emily A Vertosick; Kazuma Udo; Daniel D Sjoberg; Andrew J Vickers; Hikmat Al-Ahmadie; Ying-Bei Chen; Anuradha Gopalan; S Joseph Sirintrapun; Satish K Tickoo; Peter T Scardino; James A Eastham; Victor E Reuter; Samson W Fine Journal: BJU Int Date: 2021-07-11 Impact factor: 5.969