Timing of radiotherapy after radical prostatectomy (RADICALS-RT): a randomised, controlled phase 3 trial

Research output: Contribution to journalArticlepeer-review

Standard

Timing of radiotherapy after radical prostatectomy (RADICALS-RT) : a randomised, controlled phase 3 trial. / Parker, Christopher C; Clarke, Noel W; Cook, Adrian D; Kynaston, Howard G; Petersen, Peter Meidahl; Catton, Charles; Cross, William; Logue, John; Parulekar, Wendy; Payne, Heather; Persad, Rajendra; Pickering, Holly; Saad, Fred; Anderson, Juliette; Bahl, Amit; Bottomley, David; Brasso, Klaus; Chahal, Rohit; Cooke, Peter W; Eddy, Ben; Gibbs, Stephanie; Goh, Chee; Gujral, Sandeep; Heath, Catherine; Henderson, Alastair; Jaganathan, Ramasamy; Jakobsen, Henrik; James, Nicholas D; Kanaga Sundaram, Subramanian; Lees, Kathryn; Lester, Jason; Lindberg, Henriette; Money-kyrle, Julian; Morris, Stephen; O'sullivan, Joe; Ostler, Peter; Owen, Lisa; Patel, Prashant; Pope, Alvan; Popert, Richard; Raman, Rakesh; Røder, Martin Andreas; Sayers, Ian; Simms, Matthew; Wilson, Jim; Zarkar, Anjali; Parmar, Mahesh K B; Sydes, Matthew R.

In: The Lancet, Vol. 396, No. 10260, 31.10.2020, p. 1413-1421.

Research output: Contribution to journalArticlepeer-review

Harvard

Parker, CC, Clarke, NW, Cook, AD, Kynaston, HG, Petersen, PM, Catton, C, Cross, W, Logue, J, Parulekar, W, Payne, H, Persad, R, Pickering, H, Saad, F, Anderson, J, Bahl, A, Bottomley, D, Brasso, K, Chahal, R, Cooke, PW, Eddy, B, Gibbs, S, Goh, C, Gujral, S, Heath, C, Henderson, A, Jaganathan, R, Jakobsen, H, James, ND, Kanaga Sundaram, S, Lees, K, Lester, J, Lindberg, H, Money-kyrle, J, Morris, S, O'sullivan, J, Ostler, P, Owen, L, Patel, P, Pope, A, Popert, R, Raman, R, Røder, MA, Sayers, I, Simms, M, Wilson, J, Zarkar, A, Parmar, MKB & Sydes, MR 2020, 'Timing of radiotherapy after radical prostatectomy (RADICALS-RT): a randomised, controlled phase 3 trial', The Lancet, vol. 396, no. 10260, pp. 1413-1421. https://doi.org/10.1016/S0140-6736(20)31553-1

APA

Parker, C. C., Clarke, N. W., Cook, A. D., Kynaston, H. G., Petersen, P. M., Catton, C., Cross, W., Logue, J., Parulekar, W., Payne, H., Persad, R., Pickering, H., Saad, F., Anderson, J., Bahl, A., Bottomley, D., Brasso, K., Chahal, R., Cooke, P. W., ... Sydes, M. R. (2020). Timing of radiotherapy after radical prostatectomy (RADICALS-RT): a randomised, controlled phase 3 trial. The Lancet, 396(10260), 1413-1421. https://doi.org/10.1016/S0140-6736(20)31553-1

Vancouver

Parker CC, Clarke NW, Cook AD, Kynaston HG, Petersen PM, Catton C et al. Timing of radiotherapy after radical prostatectomy (RADICALS-RT): a randomised, controlled phase 3 trial. The Lancet. 2020 Oct 31;396(10260):1413-1421. https://doi.org/10.1016/S0140-6736(20)31553-1

Author

Parker, Christopher C ; Clarke, Noel W ; Cook, Adrian D ; Kynaston, Howard G ; Petersen, Peter Meidahl ; Catton, Charles ; Cross, William ; Logue, John ; Parulekar, Wendy ; Payne, Heather ; Persad, Rajendra ; Pickering, Holly ; Saad, Fred ; Anderson, Juliette ; Bahl, Amit ; Bottomley, David ; Brasso, Klaus ; Chahal, Rohit ; Cooke, Peter W ; Eddy, Ben ; Gibbs, Stephanie ; Goh, Chee ; Gujral, Sandeep ; Heath, Catherine ; Henderson, Alastair ; Jaganathan, Ramasamy ; Jakobsen, Henrik ; James, Nicholas D ; Kanaga Sundaram, Subramanian ; Lees, Kathryn ; Lester, Jason ; Lindberg, Henriette ; Money-kyrle, Julian ; Morris, Stephen ; O'sullivan, Joe ; Ostler, Peter ; Owen, Lisa ; Patel, Prashant ; Pope, Alvan ; Popert, Richard ; Raman, Rakesh ; Røder, Martin Andreas ; Sayers, Ian ; Simms, Matthew ; Wilson, Jim ; Zarkar, Anjali ; Parmar, Mahesh K B ; Sydes, Matthew R. / Timing of radiotherapy after radical prostatectomy (RADICALS-RT) : a randomised, controlled phase 3 trial. In: The Lancet. 2020 ; Vol. 396, No. 10260. pp. 1413-1421.

Bibtex

@article{0340fc9b739e402b856a9a669fc2a506,
title = "Timing of radiotherapy after radical prostatectomy (RADICALS-RT): a randomised, controlled phase 3 trial",
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.",
author = "Parker, {Christopher C} and Clarke, {Noel W} and Cook, {Adrian D} and Kynaston, {Howard G} and Petersen, {Peter Meidahl} and Charles Catton and William Cross and John Logue and Wendy Parulekar and Heather Payne and Rajendra Persad and Holly Pickering and Fred Saad and Juliette Anderson and Amit Bahl and David Bottomley and Klaus Brasso and Rohit Chahal and Cooke, {Peter W} and Ben Eddy and Stephanie Gibbs and Chee Goh and Sandeep Gujral and Catherine Heath and Alastair Henderson and Ramasamy Jaganathan and Henrik Jakobsen and James, {Nicholas D} and {Kanaga Sundaram}, Subramanian and Kathryn Lees and Jason Lester and Henriette Lindberg and Julian Money-kyrle and Stephen Morris and Joe O'sullivan and Peter Ostler and Lisa Owen and Prashant Patel and Alvan Pope and Richard Popert and Rakesh Raman and R{\o}der, {Martin Andreas} and Ian Sayers and Matthew Simms and Jim Wilson and Anjali Zarkar and Parmar, {Mahesh K B} and Sydes, {Matthew R}",
year = "2020",
month = oct,
day = "31",
doi = "10.1016/S0140-6736(20)31553-1",
language = "English",
volume = "396",
pages = "1413--1421",
journal = "The Lancet",
issn = "0140-6736",
publisher = "Elsevier",
number = "10260",

}

RIS

TY - JOUR

T1 - Timing of radiotherapy after radical prostatectomy (RADICALS-RT)

T2 - a randomised, controlled phase 3 trial

AU - Parker, Christopher C

AU - Clarke, Noel W

AU - Cook, Adrian D

AU - Kynaston, Howard G

AU - Petersen, Peter Meidahl

AU - Catton, Charles

AU - Cross, William

AU - Logue, John

AU - Parulekar, Wendy

AU - Payne, Heather

AU - Persad, Rajendra

AU - Pickering, Holly

AU - Saad, Fred

AU - Anderson, Juliette

AU - Bahl, Amit

AU - Bottomley, David

AU - Brasso, Klaus

AU - Chahal, Rohit

AU - Cooke, Peter W

AU - Eddy, Ben

AU - Gibbs, Stephanie

AU - Goh, Chee

AU - Gujral, Sandeep

AU - Heath, Catherine

AU - Henderson, Alastair

AU - Jaganathan, Ramasamy

AU - Jakobsen, Henrik

AU - James, Nicholas D

AU - Kanaga Sundaram, Subramanian

AU - Lees, Kathryn

AU - Lester, Jason

AU - Lindberg, Henriette

AU - Money-kyrle, Julian

AU - Morris, Stephen

AU - O'sullivan, Joe

AU - Ostler, Peter

AU - Owen, Lisa

AU - Patel, Prashant

AU - Pope, Alvan

AU - Popert, Richard

AU - Raman, Rakesh

AU - Røder, Martin Andreas

AU - Sayers, Ian

AU - Simms, Matthew

AU - Wilson, Jim

AU - Zarkar, Anjali

AU - Parmar, Mahesh K B

AU - Sydes, Matthew R

PY - 2020/10/31

Y1 - 2020/10/31

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85091664198&partnerID=8YFLogxK

U2 - 10.1016/S0140-6736(20)31553-1

DO - 10.1016/S0140-6736(20)31553-1

M3 - Article

VL - 396

SP - 1413

EP - 1421

JO - The Lancet

JF - The Lancet

SN - 0140-6736

IS - 10260

ER -