Ten-year Mortality, Disease Progression, and Treatment-related Side Effects in Men with Localised Prostate Cancer from the ProtecT Randomised Controlled Trial According to Treatment Received
Authors: David E. Neal, Chris Metcalfe, Jenny L. Donovan, J. Athene Lane, Michael Davis, Grace J. Young, Susan J. Dutton, Eleanor I. Walsh, Richard M. Martin, Tim. J. Peters, Emma L. Turner, Malcolm Mason, Richard Bryant, Prasad Bollina, James Catto, Alan Doherty, David Gillatt, Vincent Gnanapragasam, Peter Holding, Owen Hughes, Roger Kockelbergh, Howard Kynaston, Jon Oxley, Alan Paul, Edgar Paez, Derek J. Rosario, Edward Rowe, John Staffurth, Doug G. Altman, Freddie C. Hamdy, Freddie C. Hamdy, Jenny L. Donovan, David E. Neal, J. Athene Lane, Chris Metcalfe, Tim J. Peters, Prasad Bollina, Andrew Doble, Alan Doherty, Vincent Gnanapragasam, Owen Hughes, David Gillatt, Roger Kockelbergh, Howard Kynaston, Alan Paul, Edgar Paez, Philip Powell, Stephen Prescott, Derek Rosario, Edward Rowe, John B. Anderson, Jonathan Aning, James Catto, Garett Durkan, Anthony Koupparis, Hing Leung, Param Mariappan, Alan McNeill, Raj Persad, Hartwig Schwaibold, David Tulloch, Michael Wallace, Susan Bonnington, Lynne Bradshaw, Deborah Cooper, Emma Elliott, Phillipa Herbert, Peter Holding, Joanne Howson, Amanda Jones, Teresa Lennon, Norma Lyons, Hilary Moody, Claire Plumb, Tricia O'Sullivan, Elizabeth Salter, Pauline Thompson, Sarah Tidball, Jan Blaikie, Catherine Gray, Tonia Adam, Sarah Askew, Sharon Atkinson, Tim Baynes, Carole Brain, Viv Breen, Sarah Brunt, Sean Bryne, Jo Bythem, Jenny Clarke, Jenny Cloete, Susan Dark, Gill Davis, Rachael De La Rue, Jane Denizot, Elspeth Dewhurst, Anna Dimes, Nicola Dixon, Penny Ebbs, Ingrid Emmerson, Jill Ferguson, Ali Gadd, Lisa Geoghegan, Alison Grant, Collette Grant, Rosemary Godfrey, Louise Goodwin, Susie Hall, Liz Hart, Andrew Harvey, Chloe Hoult, Sarah Hawkins, Sharon Holling, Alastair Innes, Sue Kilner, Fiona Marshall, Louise Mellen, Andrea Moore, Sally Napier, Julie Needham, Kevin Pearse, Anna Pisa, Mark Rees, Ellie Richards, Lindsay Robson, Janet Roxburgh, Nikki Samuel, Irene Sharkey, Michael Slater, Donna Smith, Pippa Taggart, Helen Taylor, Vicky Taylor, Ayesha Thomas, Briony Tomkies, Nicola Trewick, Claire Ward, Christy Walker, Ayesha Williams, Colin Woodhouse, Elizabeth Wyber, Malcolm Mason, Amit Bahl, Richard Benson, Mark Beresford, Catherine Ferguson, John Graham, Chris Herbert, Grahame Howard, Nick James, Peter Kirkbride, Alastair Law, Carmel Loughrey, Duncan McClaren, Helen Patterson, Ian Pedley, Trevor Roberts, Angus Robinson, Simon Russell, John Staffurth, Paul Symonds, Narottam Thanvi, Subramaniam Vasanthan, Paula Wilson, Jon Oxley, Mary Robinson, Selina Bhattarai, Neeta Deshmukh, John Dormer, Malee Fernando, John Goepel, David Griffiths, Ken Grigor, Nick Mayer, Murali Varma, Anne Warren, Helen Appleby, Dominic Ash, Dean Aston, Steven Bolton, Graham Chalmers, John Conway, Nick Early, Tony Geater, Lynda Goddall, Claire Heymann, Deborah Hicks, Liza Jones, Susan Lamb, Geoff Lambert, Gill Lawrence, Geraint Lewis, John Lilley, Aileen MacLeod, Pauline Massey, Alison McQueen, Rollo Moore, Lynda Penketh, Janet Potterton, Neil Roberts, Helen Showler, Pam Shuttleworth, Stephen Slade, Alasdair Steele, James Swinscoe, Marie Tiffany, John Townley, Jo Treeby, Michael Weston, Joyce Wilkinson, Lorraine Williams, Lucy Wills, Owain Woodley, Sue Yarrow, Lucy Brindle, Linda Davies, Michael Davis, Dan Dedman, Elizabeth Down, Hanan Khazragui, Richard M. Martin, Sian Noble, Hilary Taylor, Marta Tazewell, Emma L. Turner, Julia Wade, Eleanor Walsh, Susan Baker, Elizabeth Bellis-Sheldon, Chantal Bougard, Joanne Bowtell, Catherine Brewer, Chris Burton, Jennie Charlton, Nicholas Christoforou, Rebecca Clark, Susan Coull, Christine Croker, Rosemary Currer, Claire Daisey, Gill Delaney, Rose Donohue, Jane Drew, Rebecca Farmer, Susan Fry, Jean Haddow, Alex Hale, Susan Halpin, Belle Harris, Barbara Hattrick, Sharon Holmes, Helen Hunt, Vicky Jackson, Donna Johnson, Mandy Le Butt, Jo Leworthy, Tanya Liddiatt, Alex Martin, Jainee Mauree, Susan Moore, Gill Moulam, Jackie Mutch, Kathleen Parker, Christopher Pawsey, Michelle Purdie, Teresa Robson, Lynne Smith, Carole Stenton, Tom Steuart-Feilding, Beth Stott, Chris Sully, Caroline Sutton, Carol Torrington, Zoe Wilkins, Sharon Williams, Andrea Wilson, Ashleigh Weaver, Peter Albertsen, Jan Adolfsson, Michael Baum, Jon McFarlane, Colette Reid, Emma Turner, Anthony Zietman, Elizabeth Hill, Siaw Yein Ng, Naomi Williams, Jessica Toole, Charlotte Davies, Laura Hughes, Mari-Anne Rowlands, Lindsey Bell, Sean Harrison, Jainnee Mauree, Adrian Grant, Ian Roberts, Deborah Ashby, Richard Cowan, Peter Fayers, Killian Mellon, James N’Dow, Tim O’Brien, Michael Sokhal, David Dearnaley, Fritz Schröder, Tracy Roberts, Anthony Zietman
Journal: European Urology (2019)

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. To determine report outcomes according to treatment received in men in randomised and treatment choice cohorts. 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. Two cohorts included 1643 men who agreed to be randomised; 997 declined randomisation and chose treatment. 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. 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 6 mo) and urinary incontinence (55% at 6 mo) after surgery, and of sexual dysfunction (88% at 6 mo) and bowel dysfunction (5% at 6 mo) 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. 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. More than 90 out of every 100 men with localised prostate cancer do not die of prostate cancer within 10 yr, 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.