David E Neal1, Chris Metcalfe2, Jenny L Donovan3, J Athene Lane2, Michael Davis3, Grace J Young2, Susan J Dutton4, Eleanor I Walsh3, Richard M Martin3, Tim J Peters3, Emma L Turner3, Malcolm Mason5, Richard Bryant6, Prasad Bollina7, James Catto8, Alan Doherty9, David Gillatt10, Vincent Gnanapragasam11, Peter Holding6, Owen Hughes12, Roger Kockelbergh13, Howard Kynaston14, Jon Oxley15, Alan Paul16, Edgar Paez17, Derek J Rosario18, Edward Rowe10, John Staffurth14, Doug G Altman4, Freddie C Hamdy6. 1. Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK. Electronic address: David.Neal@nds.ox.ac.uk. 2. Bristol Randomised Trials Collaboration (BRTC), Bristol Trials Centre, University of Bristol, Bristol, UK. 3. Bristol Medical School, University of Bristol, Bristol, UK. 4. Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK. 5. School of Medicine, Cardiff University, Cardiff, UK. 6. Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK. 7. Department of Urology & Surgery, Western General Hospital, University of Edinburgh, Edinburgh, UK. 8. Academic Urology Unit, University of Sheffield, Sheffield, UK. 9. Department of Urology, Queen Elizabeth Hospital, Birmingham, UK. 10. Department of Urology, Southmead Hospital and Bristol Urological Institute, Bristol, UK. 11. Academic Urology Group, Department of Surgery & Cambridge Urology Translational Research and Clinical Trials, Cambridge Biomedical Campus, University of Cambridge, Cambridge, UK. 12. Department of Urology, Cardiff and Vale University Health Board, Cardiff, UK. 13. Department of Urology, University Hospitals of Leicester, Leicester, UK. 14. Division of Cancer and Genetics, School of Medicine, Cardiff University, Cardiff, UK. 15. Department of Cellular Pathology, North Bristol NHS Trust, Bristol, UK. 16. Department of Urology, Leeds Teaching Hospitals NHS Trust, Leeds, UK. 17. Department of Urology, Freeman Hospital, Newcastle-upon-Tyne, UK. 18. Department of Urology, Royal Hallamshire Hospital, Sheffield, UK.
Abstract
BACKGROUND: The ProtecT trial reported intention-to-treat analysis of men with localised prostate cancer (PCa) randomly allocated to active monitoring (AM), radical prostatectomy, and external beam radiotherapy. OBJECTIVE: To determine report outcomes according to treatment received in men in randomised and treatment choice cohorts. DESIGN, SETTING, AND PARTICIPANTS: This study focuses on secondary care. Men with clinically localised prostate cancer at one of nine UK centres were invited to participate in the treatment trial comparing AM, radical prostatectomy, and radiotherapy. INTERVENTION: Two cohorts included 1643 men who agreed to be randomised; 997 declined randomisation and chose treatment. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Health-related quality of life impacts on urinary, bowel, and sexual function were assessed using patient-reported outcome measures. Analysis was carried out based on treatment received for each cohort and on pooled estimates using meta-analysis. Differences were estimated with adjustment for known prognostic factors using propensity scores. RESULTS AND LIMITATIONS: According to treatment received, more men receiving AM died of PCa (AM 1.85%, surgery 0.67%, radiotherapy 0.73%), whilst this difference remained consistent with chance in the randomised cohort (p=0.08); stronger evidence was found in the exploratory analyses (randomised plus choice cohort) when AM was compared with the combined radical treatment group (p=0.003). There was also strong evidence that metastasis (AM 5.6%, surgery 2.4%, radiotherapy 2.7%) and disease progression (AM 20.35%, surgery 5.87%, radiotherapy 6.62%) were more common in the AM group. Compared with AM, there were higher risks of sexual dysfunction (95% at 6mo) and urinary incontinence (55% at 6mo) after surgery, and of sexual dysfunction (88% at 6mo) and bowel dysfunction (5% at 6mo) after radiotherapy. The key limitations are the potential for bias when comparing groups defined by treatment received and outdating of the interventions being evaluated during the lengthy follow-up required in trials of screen-detected PCa. CONCLUSIONS: Analyses according to treatment received showed increased rates of disease-related events and lower rates of patient-reported harms in men managed by AM compared with men managed by radical treatment, and stronger evidence of greater PCa mortality in the AM group. PATIENT SUMMARY: More than 90 out of every 100 men with localised prostate cancer do not die of prostate cancer within 10yr, irrespective of whether treatment is by means of monitoring, surgery, or radiotherapy. Side effects on sexual and bladder function are much better after active monitoring, but the risks of spreading of prostate cancer are more common.
RCT Entities:
BACKGROUND: The ProtecT trial reported intention-to-treat analysis of men with localised prostate cancer (PCa) randomly allocated to active monitoring (AM), radical prostatectomy, and external beam radiotherapy. OBJECTIVE: To determine report outcomes according to treatment received in men in randomised and treatment choice cohorts. DESIGN, SETTING, AND PARTICIPANTS: This study focuses on secondary care. Men with clinically localised prostate cancer at one of nine UK centres were invited to participate in the treatment trial comparing AM, radical prostatectomy, and radiotherapy. INTERVENTION: Two cohorts included 1643 men who agreed to be randomised; 997 declined randomisation and chose treatment. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Health-related quality of life impacts on urinary, bowel, and sexual function were assessed using patient-reported outcome measures. Analysis was carried out based on treatment received for each cohort and on pooled estimates using meta-analysis. Differences were estimated with adjustment for known prognostic factors using propensity scores. RESULTS AND LIMITATIONS: According to treatment received, more men receiving AM died of PCa (AM 1.85%, surgery 0.67%, radiotherapy 0.73%), whilst this difference remained consistent with chance in the randomised cohort (p=0.08); stronger evidence was found in the exploratory analyses (randomised plus choice cohort) when AM was compared with the combined radical treatment group (p=0.003). There was also strong evidence that metastasis (AM 5.6%, surgery 2.4%, radiotherapy 2.7%) and disease progression (AM 20.35%, surgery 5.87%, radiotherapy 6.62%) were more common in the AM group. Compared with AM, there were higher risks of sexual dysfunction (95% at 6mo) and urinary incontinence (55% at 6mo) after surgery, and of sexual dysfunction (88% at 6mo) and bowel dysfunction (5% at 6mo) after radiotherapy. The key limitations are the potential for bias when comparing groups defined by treatment received and outdating of the interventions being evaluated during the lengthy follow-up required in trials of screen-detected PCa. CONCLUSIONS: Analyses according to treatment received showed increased rates of disease-related events and lower rates of patient-reported harms in men managed by AM compared with men managed by radical treatment, and stronger evidence of greater PCa mortality in the AM group. PATIENT SUMMARY: More than 90 out of every 100 men with localised prostate cancer do not die of prostate cancer within 10yr, irrespective of whether treatment is by means of monitoring, surgery, or radiotherapy. Side effects on sexual and bladder function are much better after active monitoring, but the risks of spreading of prostate cancer are more common.
Authors: Robin Wm Vernooij; Michelle Lancee; Anne Cleves; Philipp Dahm; Chris H Bangma; Katja Kh Aben Journal: Cochrane Database Syst Rev Date: 2020-06-04
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Authors: Shaojun Zhu; Nader Hirmas; Jeremie Calais; Matthias Eiber; Boris Hadaschik; Martin Stuschke; Ken Herrmann; Johannes Czernin; Amar U Kishan; Nicholas G Nickols; David Elashoff; Wolfgang P Fendler Journal: BMC Cancer Date: 2021-05-07 Impact factor: 4.430