Timing of radiotherapy (RT) after radical prostatectomy (RP): long-term outcomes in the RADICALS-RT trial (NCT00541047)
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Timing of radiotherapy (RT) after radical prostatectomy (RP) : long-term outcomes in the RADICALS-RT trial (NCT00541047). / Parker, C. C.; Petersen, P. M.; Cook, A. D.; Clarke, N. W.; Catton, C.; Cross, W. R.; Kynaston, H.; Parulekar, W. R.; Persad, R. A.; Saad, F.; Bower, L.; Durkan, G. C.; Logue, J.; Maniatis, C.; Noor, D.; Payne, H.; Anderson, J.; Bahl, A. K.; Bashir, F.; Bottomley, D. M.; Brasso, K.; Capaldi, L.; Chung, C.; Cooke, P. W.; Donohue, J. F.; Eddy, B.; Heath, C. M.; Henderson, A.; Henry, A.; Jaganathan, R.; Jakobsen, H.; James, N. D.; Joseph, J.; Lees, K.; Lester, J.; Lindberg, H.; Makar, A.; Morris, S. L.; Oommen, N.; Ostler, P.; Owen, L.; Patel, P.; Pope, A.; Popert, R.; Raman, R.; Ramani, V.; Røder, A.; Sayers, I.; Simms, M.; Srinivasan, V.; Sundaram, S.; Tarver, K. L.; Tran, A.; Wells, P.; Wilson, J.; Zarkar, A. M.; Parmar, M. K. B.; Sydes, M. R.; RADICALS investigators.
I: Annals of Oncology, Bind 35, Nr. 7, 2024, s. 656-666.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Timing of radiotherapy (RT) after radical prostatectomy (RP)
T2 - long-term outcomes in the RADICALS-RT trial (NCT00541047)
AU - Parker, C. C.
AU - Petersen, P. M.
AU - Cook, A. D.
AU - Clarke, N. W.
AU - Catton, C.
AU - Cross, W. R.
AU - Kynaston, H.
AU - Parulekar, W. R.
AU - Persad, R. A.
AU - Saad, F.
AU - Bower, L.
AU - Durkan, G. C.
AU - Logue, J.
AU - Maniatis, C.
AU - Noor, D.
AU - Payne, H.
AU - Anderson, J.
AU - Bahl, A. K.
AU - Bashir, F.
AU - Bottomley, D. M.
AU - Brasso, K.
AU - Capaldi, L.
AU - Chung, C.
AU - Cooke, P. W.
AU - Donohue, J. F.
AU - Eddy, B.
AU - Heath, C. M.
AU - Henderson, A.
AU - Henry, A.
AU - Jaganathan, R.
AU - Jakobsen, H.
AU - James, N. D.
AU - Joseph, J.
AU - Lees, K.
AU - Lester, J.
AU - Lindberg, H.
AU - Makar, A.
AU - Morris, S. L.
AU - Oommen, N.
AU - Ostler, P.
AU - Owen, L.
AU - Patel, P.
AU - Pope, A.
AU - Popert, R.
AU - Raman, R.
AU - Ramani, V.
AU - Røder, A.
AU - Sayers, I.
AU - Simms, M.
AU - Srinivasan, V.
AU - Sundaram, S.
AU - Tarver, K. L.
AU - Tran, A.
AU - Wells, P.
AU - Wilson, J.
AU - Zarkar, A. M.
AU - Parmar, M. K. B.
AU - Sydes, M. R.
AU - RADICALS investigators
N1 - Publisher Copyright: © 2024 The Author(s)
PY - 2024
Y1 - 2024
N2 - 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.
AB - 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.
KW - clinical trial
KW - long-term follow-up
KW - observational
KW - prostate cancer
KW - radiotherapy
KW - randomised controlled trial
U2 - 10.1016/j.annonc.2024.03.010
DO - 10.1016/j.annonc.2024.03.010
M3 - Journal article
C2 - 38583574
AN - SCOPUS:85194396910
VL - 35
SP - 656
EP - 666
JO - Annals of Oncology
JF - Annals of Oncology
SN - 0923-7534
IS - 7
ER -
ID: 395134938