Radiotherapy to the prostate for men with metastatic prostate cancer in the UK and Switzerland: Long-term results from the STAMPEDE randomised controlled trial.

<h4>Background</h4>STAMPEDE has previously reported that radiotherapy (RT) to the prostate improved overall survival (OS) for patients with newly diagnosed prostate cancer with low metastatic burden, but not those with high-burden disease. In this final analysis, we report long-term find...

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Main Authors: Chris C Parker, Nicholas D James, Christopher D Brawley, Noel W Clarke, Adnan Ali, Claire L Amos, Gerhardt Attard, Simon Chowdhury, Adrian Cook, William Cross, David P Dearnaley, Hassan Douis, Duncan C Gilbert, Clare Gilson, Silke Gillessen, Alex Hoyle, Rob J Jones, Ruth E Langley, Zafar I Malik, Malcolm D Mason, David Matheson, Robin Millman, Mary Rauchenberger, Hannah Rush, J Martin Russell, Hannah Sweeney, Amit Bahl, Alison Birtle, Lisa Capaldi, Omar Din, Daniel Ford, Joanna Gale, Ann Henry, Peter Hoskin, Mohammed Kagzi, Anna Lydon, Joe M O'Sullivan, Sangeeta A Paisey, Omi Parikh, Delia Pudney, Vijay Ramani, Peter Robson, Narayanan Nair Srihari, Jacob Tanguay, Mahesh K B Parmar, Matthew R Sydes, STAMPEDE Trial Collaborative Group
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2022-06-01
Series:PLoS Medicine
Online Access:https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1003998&type=printable
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author Chris C Parker
Nicholas D James
Christopher D Brawley
Noel W Clarke
Adnan Ali
Claire L Amos
Gerhardt Attard
Simon Chowdhury
Adrian Cook
William Cross
David P Dearnaley
Hassan Douis
Duncan C Gilbert
Clare Gilson
Silke Gillessen
Alex Hoyle
Rob J Jones
Ruth E Langley
Zafar I Malik
Malcolm D Mason
David Matheson
Robin Millman
Mary Rauchenberger
Hannah Rush
J Martin Russell
Hannah Sweeney
Amit Bahl
Alison Birtle
Lisa Capaldi
Omar Din
Daniel Ford
Joanna Gale
Ann Henry
Peter Hoskin
Mohammed Kagzi
Anna Lydon
Joe M O'Sullivan
Sangeeta A Paisey
Omi Parikh
Delia Pudney
Vijay Ramani
Peter Robson
Narayanan Nair Srihari
Jacob Tanguay
Mahesh K B Parmar
Matthew R Sydes
STAMPEDE Trial Collaborative Group
author_facet Chris C Parker
Nicholas D James
Christopher D Brawley
Noel W Clarke
Adnan Ali
Claire L Amos
Gerhardt Attard
Simon Chowdhury
Adrian Cook
William Cross
David P Dearnaley
Hassan Douis
Duncan C Gilbert
Clare Gilson
Silke Gillessen
Alex Hoyle
Rob J Jones
Ruth E Langley
Zafar I Malik
Malcolm D Mason
David Matheson
Robin Millman
Mary Rauchenberger
Hannah Rush
J Martin Russell
Hannah Sweeney
Amit Bahl
Alison Birtle
Lisa Capaldi
Omar Din
Daniel Ford
Joanna Gale
Ann Henry
Peter Hoskin
Mohammed Kagzi
Anna Lydon
Joe M O'Sullivan
Sangeeta A Paisey
Omi Parikh
Delia Pudney
Vijay Ramani
Peter Robson
Narayanan Nair Srihari
Jacob Tanguay
Mahesh K B Parmar
Matthew R Sydes
STAMPEDE Trial Collaborative Group
author_sort Chris C Parker
collection DOAJ
description <h4>Background</h4>STAMPEDE has previously reported that radiotherapy (RT) to the prostate improved overall survival (OS) for patients with newly diagnosed prostate cancer with low metastatic burden, but not those with high-burden disease. In this final analysis, we report long-term findings on the primary outcome measure of OS and on the secondary outcome measures of symptomatic local events, RT toxicity events, and quality of life (QoL).<h4>Methods and findings</h4>Patients were randomised at secondary care sites in the United Kingdom and Switzerland between January 2013 and September 2016, with 1:1 stratified allocation: 1,029 to standard of care (SOC) and 1,032 to SOC+RT. No masking of the treatment allocation was employed. A total of 1,939 had metastatic burden classifiable, with 42% low burden and 58% high burden, balanced by treatment allocation. Intention-to-treat (ITT) analyses used Cox regression and flexible parametric models (FPMs), adjusted for stratification factors age, nodal involvement, the World Health Organization (WHO) performance status, regular aspirin or nonsteroidal anti-inflammatory drug (NSAID) use, and planned docetaxel use. QoL in the first 2 years on trial was assessed using prospectively collected patient responses to QLQ-30 questionnaire. Patients were followed for a median of 61.3 months. Prostate RT improved OS in patients with low, but not high, metastatic burden (respectively: 202 deaths in SOC versus 156 in SOC+RT, hazard ratio (HR) = 0·64, 95% CI 0.52, 0.79, p < 0.001; 375 SOC versus 386 SOC+RT, HR = 1.11, 95% CI 0.96, 1.28, p = 0·164; interaction p < 0.001). No evidence of difference in time to symptomatic local events was found. There was no evidence of difference in Global QoL or QLQ-30 Summary Score. Long-term urinary toxicity of grade 3 or worse was reported for 10 SOC and 10 SOC+RT; long-term bowel toxicity of grade 3 or worse was reported for 15 and 11, respectively.<h4>Conclusions</h4>Prostate RT improves OS, without detriment in QoL, in men with low-burden, newly diagnosed, metastatic prostate cancer, indicating that it should be recommended as a SOC.<h4>Trial registration</h4>ClinicalTrials.gov NCT00268476, ISRCTN.com ISRCTN78818544.
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spelling doaj-art-6362f7c1f7f944ef83cd0276f5fe81432025-08-20T03:46:25ZengPublic Library of Science (PLoS)PLoS Medicine1549-12771549-16762022-06-01196e100399810.1371/journal.pmed.1003998Radiotherapy to the prostate for men with metastatic prostate cancer in the UK and Switzerland: Long-term results from the STAMPEDE randomised controlled trial.Chris C ParkerNicholas D JamesChristopher D BrawleyNoel W ClarkeAdnan AliClaire L AmosGerhardt AttardSimon ChowdhuryAdrian CookWilliam CrossDavid P DearnaleyHassan DouisDuncan C GilbertClare GilsonSilke GillessenAlex HoyleRob J JonesRuth E LangleyZafar I MalikMalcolm D MasonDavid MathesonRobin MillmanMary RauchenbergerHannah RushJ Martin RussellHannah SweeneyAmit BahlAlison BirtleLisa CapaldiOmar DinDaniel FordJoanna GaleAnn HenryPeter HoskinMohammed KagziAnna LydonJoe M O'SullivanSangeeta A PaiseyOmi ParikhDelia PudneyVijay RamaniPeter RobsonNarayanan Nair SrihariJacob TanguayMahesh K B ParmarMatthew R SydesSTAMPEDE Trial Collaborative Group<h4>Background</h4>STAMPEDE has previously reported that radiotherapy (RT) to the prostate improved overall survival (OS) for patients with newly diagnosed prostate cancer with low metastatic burden, but not those with high-burden disease. In this final analysis, we report long-term findings on the primary outcome measure of OS and on the secondary outcome measures of symptomatic local events, RT toxicity events, and quality of life (QoL).<h4>Methods and findings</h4>Patients were randomised at secondary care sites in the United Kingdom and Switzerland between January 2013 and September 2016, with 1:1 stratified allocation: 1,029 to standard of care (SOC) and 1,032 to SOC+RT. No masking of the treatment allocation was employed. A total of 1,939 had metastatic burden classifiable, with 42% low burden and 58% high burden, balanced by treatment allocation. Intention-to-treat (ITT) analyses used Cox regression and flexible parametric models (FPMs), adjusted for stratification factors age, nodal involvement, the World Health Organization (WHO) performance status, regular aspirin or nonsteroidal anti-inflammatory drug (NSAID) use, and planned docetaxel use. QoL in the first 2 years on trial was assessed using prospectively collected patient responses to QLQ-30 questionnaire. Patients were followed for a median of 61.3 months. Prostate RT improved OS in patients with low, but not high, metastatic burden (respectively: 202 deaths in SOC versus 156 in SOC+RT, hazard ratio (HR) = 0·64, 95% CI 0.52, 0.79, p < 0.001; 375 SOC versus 386 SOC+RT, HR = 1.11, 95% CI 0.96, 1.28, p = 0·164; interaction p < 0.001). No evidence of difference in time to symptomatic local events was found. There was no evidence of difference in Global QoL or QLQ-30 Summary Score. Long-term urinary toxicity of grade 3 or worse was reported for 10 SOC and 10 SOC+RT; long-term bowel toxicity of grade 3 or worse was reported for 15 and 11, respectively.<h4>Conclusions</h4>Prostate RT improves OS, without detriment in QoL, in men with low-burden, newly diagnosed, metastatic prostate cancer, indicating that it should be recommended as a SOC.<h4>Trial registration</h4>ClinicalTrials.gov NCT00268476, ISRCTN.com ISRCTN78818544.https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1003998&type=printable
spellingShingle Chris C Parker
Nicholas D James
Christopher D Brawley
Noel W Clarke
Adnan Ali
Claire L Amos
Gerhardt Attard
Simon Chowdhury
Adrian Cook
William Cross
David P Dearnaley
Hassan Douis
Duncan C Gilbert
Clare Gilson
Silke Gillessen
Alex Hoyle
Rob J Jones
Ruth E Langley
Zafar I Malik
Malcolm D Mason
David Matheson
Robin Millman
Mary Rauchenberger
Hannah Rush
J Martin Russell
Hannah Sweeney
Amit Bahl
Alison Birtle
Lisa Capaldi
Omar Din
Daniel Ford
Joanna Gale
Ann Henry
Peter Hoskin
Mohammed Kagzi
Anna Lydon
Joe M O'Sullivan
Sangeeta A Paisey
Omi Parikh
Delia Pudney
Vijay Ramani
Peter Robson
Narayanan Nair Srihari
Jacob Tanguay
Mahesh K B Parmar
Matthew R Sydes
STAMPEDE Trial Collaborative Group
Radiotherapy to the prostate for men with metastatic prostate cancer in the UK and Switzerland: Long-term results from the STAMPEDE randomised controlled trial.
PLoS Medicine
title Radiotherapy to the prostate for men with metastatic prostate cancer in the UK and Switzerland: Long-term results from the STAMPEDE randomised controlled trial.
title_full Radiotherapy to the prostate for men with metastatic prostate cancer in the UK and Switzerland: Long-term results from the STAMPEDE randomised controlled trial.
title_fullStr Radiotherapy to the prostate for men with metastatic prostate cancer in the UK and Switzerland: Long-term results from the STAMPEDE randomised controlled trial.
title_full_unstemmed Radiotherapy to the prostate for men with metastatic prostate cancer in the UK and Switzerland: Long-term results from the STAMPEDE randomised controlled trial.
title_short Radiotherapy to the prostate for men with metastatic prostate cancer in the UK and Switzerland: Long-term results from the STAMPEDE randomised controlled trial.
title_sort radiotherapy to the prostate for men with metastatic prostate cancer in the uk and switzerland long term results from the stampede randomised controlled trial
url https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1003998&type=printable
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