Timing of radiotherapy (RT) after radical prostatectomy (RP): long-term outcomes in the RADICALS-RT trial (NCT00541047).

Autor:	Parker CC; Institute of Cancer Research, Royal Marsden NHS Foundation Trust, Sutton, UK. Electronic address: chris.parker@rmh.nhs.uk., Petersen PM; Department of Oncology, Copenhagen Prostate Cancer Center, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark., Cook AD; MRC Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, UCL, London., Clarke NW; Department of Urology, The Christie NHS Foundation Trust, Manchester; Manchester Cancer Research Centre, The University of Manchester, Manchester; Department of Urology, Salford Royal NHS Foundation Trust, Manchester, UK, Department of Urology, Wythenshawe Hospital, Manchester University NHS Foundation Trust, Manchester, UK., Catton C; Department of Radiation Oncology, Princess Margaret Cancer Centre, University Health Network, Toronto, Canada., Cross WR; Department of Urology, St James's University Hospital, Leeds., Kynaston H; Division of Cancer and Genetics, Cardiff University, Cardiff, UK., Parulekar WR; Canadian Cancer Trials Group, Queen's University, Kingston, Canada., Persad RA; Department of Urology, Bristol Urological Institute, Bristol, UK., Saad F; Department of Urology, Centre Hospitalier de l'Université de Montréal, Montreal, Canada., Bower L; Guy's and St Thomas' NHS Foundation Trust, London; Institute of Cancer Research, Royal Marsden NHS Foundation Trust, London, UK., Durkan GC; Department of Urology, University Hospital Galway, Galway, Ireland., Logue J; Department of Oncology, The Christie Hospital NHS FT, Wilmslow Road, Manchester., Maniatis C; MRC Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, UCL, London., Noor D; MRC Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, UCL, London., Payne H; The Prostate Centre, London., Anderson J; St James's Institute of Oncology, Leeds., Bahl AK; Bristol Haematology and Oncology Centre, University Hospitals Bristol & Weston NHS Trust, Bristol., Bashir F; Queen's Centre for Oncology, Castle Hill Hospital, Hull University Teaching Hospitals NHS Trust, Cottingham, UK., Bottomley DM; St James's Institute of Oncology, Leeds., Brasso K; Department of Urology, Copenhagen Prostate Cancer Center, Copenhagen University Hospital, Rigshospitalet, Copenhagen; Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark., Capaldi L; Worcester Oncology Centre, Worcestershire Acute NHS Hospitals Trust, Worcester., Chung C; MRC Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, UCL, London., Cooke PW; Department of Urology, The Royal Wolverhampton NHS Trust, Wolverhampton., Donohue JF; Department of Urology, Maidstone and Tunbridge Wells NHS Trust, Maidstone., Eddy B; East Kent University Hospitals Foundation Trust, Kent., Heath CM; Department of Clinical Oncology, University Hospital Southampton NHS Foundation Trust, Southampton., Henderson A; Department of Urology, Maidstone and Tunbridge Wells NHS Trust, Maidstone., Henry A; Leeds Institute of Medical Research, University of Leeds, Leeds., Jaganathan R; Department of Urology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK., Jakobsen H; Department of Urology, Herlev University Hospital, Herlev, Denmark., James ND; Institute of Cancer Research, Royal Marsden NHS Foundation Trust, London, UK., Joseph J; Leeds Teaching Hospitals; York and Scarborough Teaching Hospitals, York., Lees K; Kent Oncology Centre, Maidstone and Tunbridge Wells NHS Trust, Maidstone., Lester J; South West Wales Cancer Centre, Singleton Hospital, Swansea, UK., Lindberg H; Department of Oncology, Herlev University Hospital, Herlev, Denmark., Makar A; Department of Urology, Worcestershire Acute Hospitals Trust, Worcester., Morris SL; Guy's and St Thomas' NHS Foundation Trust, London., Oommen N; Wrexham Maelor Hospital, Wrexham., Ostler P; Department of Urology, Hillingdon Hospitals NHS Foundation Trust, Hillingdon, London., Owen L; Bradford Royal Infirmary, Bradford; Leeds Cancer Centre, Leeds., Patel P; Department of Urology, University College London Hospitals, London., Pope A; Department of Urology, Hillingdon Hospitals NHS Foundation Trust, Hillingdon, London., Popert R; Guy's and St Thomas' NHS Foundation Trust, London., Raman R; Kent Oncology Centre, Kent & Canterbury Hospital, Canterbury., Ramani V; Department of Urology, The Christie NHS Foundation Trust, Manchester., Røder A; Department of Urology, Copenhagen Prostate Cancer Center, Copenhagen University Hospital, Rigshospitalet, Copenhagen., Sayers I; Deanesly Centre, New Cross Hospital, Wolverhampton., Simms M; Department of Urology, Hull University Hospitals NHS Trust, Hull., Srinivasan V; Glan Clwyd Hospital, Betsi Cadwaladr University Health Board, Rhyl., Sundaram S; Department of Urology, Mid Yorkshire Teaching Hospital, Wakefield., Tarver KL; Department of Oncology, Queen's Hospital, Romford., Tran A; Department of Oncology, The Christie Hospital NHS FT, Wilmslow Road, Manchester., Wells P; Barts Cancer Centre, St Bartholomews Hospital, London., Wilson J; Royal Gwent Hospital, Newport., Zarkar AM; Department of Oncology, University Hospitals Birmingham, Birmingham, UK., Parmar MKB; MRC Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, UCL, London., Sydes MR; MRC Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, UCL, London. Electronic address: mrcctu.radicals@ucl.ac.uk.
Jazyk:	angličtina
Zdroj:	Annals of oncology : official journal of the European Society for Medical Oncology [Ann Oncol] 2024 Jul; Vol. 35 (7), pp. 656-666. Date of Electronic Publication: 2024 Apr 05.
DOI:	10.1016/j.annonc.2024.03.010
Abstrakt:	Background: 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 prostate-specific antigen (PSA) failure. Patients and Methods: RADICALS-RT was a randomised controlled trial enrolling patients with ≥1 risk factor (pT3/4, Gleason 7-10, positive margins, preoperative PSA≥10 ng/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≥0.1 ng/ml or three consecutive rises. Stratification factors were Gleason score, margin status, planned RT schedule (52.5 Gy/20 fractions or 66 Gy/33 fractions) and treatment centre. The primary outcome measure was freedom-from-distant-metastasis (FFDM), designed with 80% power to detect an improvement from 90% with Salvage-RT (control) to 95% at 10 years with Adjuvant-RT. Secondary outcome measures were biochemical progression-free survival, freedom from non-protocol hormone therapy, safety and patient-reported outcomes. Standard survival analysis methods were used; hazard ratio (HR)<1 favours Adjuvant-RT. Results: Between October 2007 and December 2016, 1396 participants from UK, Denmark, Canada and Ireland were randomised: 699 Salvage-RT, 697 Adjuvant-RT. Allocated groups were balanced with a median age of 65 years. Ninety-three percent (649/697) Adjuvant-RT reported RT within 6 months after randomisation; 39% (270/699) Salvage-RT reported RT during follow-up. Median follow-up was 7.8 years. With 80 distant metastasis events, 10-year FFDM was 93% for Adjuvant-RT and 90% for Salvage-RT: HR=0.68 [95% confidence interval (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 1 year after randomisation (P=0.001); faecal incontinence remained significant after 10 years (P=0.017). Conclusion: 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. Trial Identification: RADICALS, RADICALS-RT, ISRCTN40814031, NCT00541047. (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
Databáze:	MEDLINE
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