Timing of Radiotherapy (RT) After Radical Prostatectomy (RP): Long-term outcomes in the RADICALS-RT trial [NCT00541047]

C C Parker; P M Petersen; A D Cook; N W Clarke; C Catton; W R Cross; H Kynaston; W R Parulekar; R A Persad; F Saad; L Bower; G C Durkan; J Logue; C Maniatis; D Noor; H Payne; J Anderson; A K Bahl; F Bashir; D M Bottomley; K Brasso; L Capaldi; P W Cooke; C Chung; J Donohue; B Eddy; C M Heath; A Henderson; A Henry; R Jaganathan; H Jakobsen; N D James; J Joseph; K Lees; J Lester; H Lindberg; A Makar; S L Morris; N Oommen; P Ostler; L Owen; P Patel; A Pope; R Popert; R Raman; V Ramani; A Røder; I Sayers; M Simms; V Srinivasan; RADICALS investigators; Matthew R Sydes

doi:10.1016/j.annonc.2024.03.010

Timing of Radiotherapy (RT) After Radical Prostatectomy (RP): Long-term outcomes in the RADICALS-RT trial [NCT00541047]

C C Parker^*, P M Petersen, A D Cook, N W Clarke, C Catton, W R Cross, H Kynaston, W R Parulekar, R A Persad, F Saad, L Bower, G C Durkan, J Logue, C Maniatis, D Noor, H Payne, J Anderson, A K Bahl, F Bashir, D M BottomleyK Brasso, L Capaldi, P W Cooke, C Chung, J Donohue, B Eddy, C M Heath, A Henderson, A Henry, R Jaganathan, H Jakobsen, N D James, J Joseph, K Lees, J Lester, H Lindberg, A Makar, S L Morris, N Oommen, P Ostler, L Owen, P Patel, A Pope, R Popert, R Raman, V Ramani, A Røder, I Sayers, M Simms, V Srinivasan, RADICALS investigators, Matthew R Sydes^*

^*Corresponding author for this work

8 Citations (Scopus)

Abstract

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.

Original language	English
Journal	Annals of Oncology
Volume	35
Issue number	7
Pages (from-to)	656-666
Number of pages	11
ISSN	0923-7534
DOIs	https://doi.org/10.1016/j.annonc.2024.03.010
Publication status	Published - Jul 2024

Keywords

clinical trial
long-term follow-up
observational
prostate cancer
radiotherapy
randomised controlled trial
Prostatic Neoplasms/radiotherapy
Humans
Middle Aged
Radiotherapy, Adjuvant/adverse effects
Salvage Therapy/methods
Prostatectomy/methods
Male
Neoplasm Recurrence, Local/pathology
Prostate-Specific Antigen/blood
Neoplasm Grading
Time Factors
Aged

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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., ... Sydes, M. R. (2024). Timing of Radiotherapy (RT) After Radical Prostatectomy (RP): Long-term outcomes in the RADICALS-RT trial [NCT00541047]. Annals of Oncology, 35(7), 656-666. https://doi.org/10.1016/j.annonc.2024.03.010

Parker, CC, Petersen, PM, Cook, AD, Clarke, NW, Catton, C, Cross, WR, Kynaston, H, Parulekar, WR, Persad, RA, Saad, F, Bower, L, Durkan, GC, Logue, J, Maniatis, C, Noor, D, Payne, H, Anderson, J, Bahl, AK, Bashir, F, Bottomley, DM, Brasso, K, Capaldi, L, Cooke, PW, Chung, C, Donohue, J, Eddy, B, Heath, CM, Henderson, A, Henry, A, Jaganathan, R, Jakobsen, H, James, ND, Joseph, J, Lees, K, Lester, J, Lindberg, H, Makar, A, Morris, SL, Oommen, N, Ostler, P, Owen, L, Patel, P, Pope, A, Popert, R, Raman, R, Ramani, V, Røder, A, Sayers, I, Simms, M, Srinivasan, V, RADICALS investigators & Sydes, MR 2024, 'Timing of Radiotherapy (RT) After Radical Prostatectomy (RP): Long-term outcomes in the RADICALS-RT trial [NCT00541047]', Annals of Oncology, vol. 35, no. 7, pp. 656-666. https://doi.org/10.1016/j.annonc.2024.03.010

@article{413aab5ac2d240fab38db1087609a465,

title = "Timing of Radiotherapy (RT) After Radical Prostatectomy (RP): Long-term outcomes in the RADICALS-RT trial [NCT00541047]",

abstract = "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.",

keywords = "clinical trial, long-term follow-up, observational, prostate cancer, radiotherapy, randomised controlled trial, Prostatic Neoplasms/radiotherapy, Humans, Middle Aged, Radiotherapy, Adjuvant/adverse effects, Salvage Therapy/methods, Prostatectomy/methods, Male, Neoplasm Recurrence, Local/pathology, Prostate-Specific Antigen/blood, Neoplasm Grading, Time Factors, Aged",

author = "Parker, {C C} and Petersen, {P M} and Cook, {A D} and Clarke, {N W} and C Catton and Cross, {W R} and H Kynaston and Parulekar, {W R} and Persad, {R A} and F Saad and L Bower and Durkan, {G C} and J Logue and C Maniatis and D Noor and H Payne and J Anderson and Bahl, {A K} and F Bashir and Bottomley, {D M} and K Brasso and L Capaldi and Cooke, {P W} and C Chung and J Donohue and B Eddy and Heath, {C M} and A Henderson and A Henry and R Jaganathan and H Jakobsen and James, {N D} and J Joseph and K Lees and J Lester and H Lindberg and A Makar and Morris, {S L} and N Oommen and P Ostler and L Owen and P Patel and A Pope and R Popert and R Raman and V Ramani and A R{\o}der and I Sayers and M Simms and V Srinivasan and {RADICALS investigators} and Sydes, {Matthew R}",

year = "2024",

month = jul,

doi = "10.1016/j.annonc.2024.03.010",

language = "English",

volume = "35",

pages = "656--666",

journal = "Annals of Oncology",

issn = "0923-7534",

publisher = "Oxford University Press",

number = "7",

}

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 - Cooke, P W

AU - Chung, C

AU - Donohue, J

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 - RADICALS investigators

AU - Sydes, Matthew R

PY - 2024/7

Y1 - 2024/7

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

KW - Prostatic Neoplasms/radiotherapy

KW - Humans

KW - Middle Aged

KW - Radiotherapy, Adjuvant/adverse effects

KW - Salvage Therapy/methods

KW - Prostatectomy/methods

KW - Male

KW - Neoplasm Recurrence, Local/pathology

KW - Prostate-Specific Antigen/blood

KW - Neoplasm Grading

KW - Time Factors

KW - Aged

UR - http://www.scopus.com/inward/record.url?scp=85194396910&partnerID=8YFLogxK

U2 - 10.1016/j.annonc.2024.03.010

DO - 10.1016/j.annonc.2024.03.010

M3 - Journal article

C2 - 38583574

SN - 0923-7534

VL - 35

SP - 656

EP - 666

JO - Annals of Oncology

JF - Annals of Oncology

IS - 7

ER -

Timing of Radiotherapy (RT) After Radical Prostatectomy (RP): Long-term outcomes in the RADICALS-RT trial [NCT00541047]

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