Randomised Trial of No, Short-term, or Long-term Androgen Deprivation Therapy with Postoperative Radiotherapy After Radical Prostatectomy: Results from the Three-way Comparison of RADICALS-HD (NCT00541047)

Chris C Parker; Noel W Clarke; Adrian D Cook; Peter M Petersen; Charles N Catton; William R Cross; Howard Kynaston; Raj A Persad; Fred Saad; John Logue; Heather Payne; Claire Amos; Lorna Bower; Rakesh Raman; Ian Sayers; Jane Worlding; Wendy R Parulekar; Mahesh K B Parmar; Matthew R Sydes; RADICALS investigators

doi:10.1016/j.eururo.2024.07.026

Randomised Trial of No, Short-term, or Long-term Androgen Deprivation Therapy with Postoperative Radiotherapy After Radical Prostatectomy: Results from the Three-way Comparison of RADICALS-HD (NCT00541047)

Chris C Parker, Noel W Clarke, Adrian D Cook, Peter M Petersen, Charles N Catton, William R Cross, Howard Kynaston, Raj A Persad, Fred Saad, John Logue, Heather Payne, Claire Amos, Lorna Bower, Rakesh Raman, Ian Sayers, Jane Worlding, Wendy R Parulekar, Mahesh K B Parmar, Matthew R Sydes^*, RADICALS investigators

^*Corresponding author for this work

Department of Oncology

Abstract

BACKGROUND AND OBJECTIVE: The use and duration of androgen deprivation therapy (ADT) with postoperative radiotherapy (RT) have been uncertain. RADICALS-HD compared adding no ("None"), 6-months ("Short"), or 24-mo ("Long") ADT to study efficacy in the long term.

METHODS: Participants with prostate cancer were indicated for postoperative RT and agreed randomisation between all durations. ADT was allocated for 0, 6, or 24 mo. The primary outcome measure (OM) was metastasis-free survival (MFS). The secondary OMs included freedom from distant metastasis, overall survival, and initiation of nonprotocol ADT. Sample size was determined by two-way comparisons. Analyses followed standard time-to-event approaches and intention-to-treat principles.

KEY FINDINGS AND LIMITATIONS: Between 2007 and 2015, 492 participants were randomised one of three groups: 166 None, 164 Short, and 162 Long. The median age at randomisation was 66 yr; Gleason scores at surgery were as follows: <7 = 64 (13%), 3+4 = 229 (47%), 4+3 = 127 (26%), and 8+ = 72 (15%); T3b was 112 (23%); and T4 was 5 (1%). The median follow-up was 9.0 yr and, with MFS events reported for 89 participants (32 None, 31 Short, and 26 Long), there was no evidence of difference in MFS overall (logrank p = 0.98), and, for Long versus None, hazard ratio = 0.948 (95% confidence interval 0.54-1.68). After 10 yr, 80% None, 77% Short, and 81% Long patients were alive without metastatic disease. The three-way randomisation was not powered to conventional levels for assessment, yet provides a fair comparison.

CONCLUSIONS AND CLINICAL IMPLICATIONS: Long-term outcomes after radical prostatectomy are usually favourable. In those indicated for postoperative RT and considered suitable for no, short-term, or long-term ADT, there was no evidence of improvement with addition of ADT. Future research should focus on patients at a higher risk of metastases in whom improvements are required more urgently.

Original language	English
Journal	European Urology
ISSN	0302-2838
DOIs	https://doi.org/10.1016/j.eururo.2024.07.026
Publication status	E-pub ahead of print - 30 Aug 2024

Keywords

Androgen deprivation therapy
Clinical trials
Duration
Hormone therapy
Multiarm trial
Prostate cancer
Radical prostatectomy
Radiotherapy
Randomised controlled trial

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Parker, C. C., Clarke, N. W., Cook, A. D., Petersen, P. M., Catton, C. N., Cross, W. R., Kynaston, H., Persad, R. A., Saad, F., Logue, J., Payne, H., Amos, C., Bower, L., Raman, R., Sayers, I., Worlding, J., Parulekar, W. R., Parmar, M. K. B., Sydes, M. R., & RADICALS investigators (2024). Randomised Trial of No, Short-term, or Long-term Androgen Deprivation Therapy with Postoperative Radiotherapy After Radical Prostatectomy: Results from the Three-way Comparison of RADICALS-HD (NCT00541047). European Urology. Advance online publication. https://doi.org/10.1016/j.eururo.2024.07.026

Randomised Trial of No, Short-term, or Long-term Androgen Deprivation Therapy with Postoperative Radiotherapy After Radical Prostatectomy: Results from the Three-way Comparison of RADICALS-HD (NCT00541047). / Parker, Chris C; Clarke, Noel W; Cook, Adrian D et al.
In: European Urology, 30.08.2024.

Research output: Contribution to journal › Journal article › Research › peer-review

Parker, CC, Clarke, NW, Cook, AD, Petersen, PM, Catton, CN, Cross, WR, Kynaston, H, Persad, RA, Saad, F, Logue, J, Payne, H, Amos, C, Bower, L, Raman, R, Sayers, I, Worlding, J, Parulekar, WR, Parmar, MKB, Sydes, MR & RADICALS investigators 2024, 'Randomised Trial of No, Short-term, or Long-term Androgen Deprivation Therapy with Postoperative Radiotherapy After Radical Prostatectomy: Results from the Three-way Comparison of RADICALS-HD (NCT00541047)', European Urology. https://doi.org/10.1016/j.eururo.2024.07.026

@article{1ebca83283a540dc9cbca4b7811a6e10,

title = "Randomised Trial of No, Short-term, or Long-term Androgen Deprivation Therapy with Postoperative Radiotherapy After Radical Prostatectomy: Results from the Three-way Comparison of RADICALS-HD (NCT00541047)",

abstract = "BACKGROUND AND OBJECTIVE: The use and duration of androgen deprivation therapy (ADT) with postoperative radiotherapy (RT) have been uncertain. RADICALS-HD compared adding no ({"}None{"}), 6-months ({"}Short{"}), or 24-mo ({"}Long{"}) ADT to study efficacy in the long term.METHODS: Participants with prostate cancer were indicated for postoperative RT and agreed randomisation between all durations. ADT was allocated for 0, 6, or 24 mo. The primary outcome measure (OM) was metastasis-free survival (MFS). The secondary OMs included freedom from distant metastasis, overall survival, and initiation of nonprotocol ADT. Sample size was determined by two-way comparisons. Analyses followed standard time-to-event approaches and intention-to-treat principles.KEY FINDINGS AND LIMITATIONS: Between 2007 and 2015, 492 participants were randomised one of three groups: 166 None, 164 Short, and 162 Long. The median age at randomisation was 66 yr; Gleason scores at surgery were as follows: <7 = 64 (13%), 3+4 = 229 (47%), 4+3 = 127 (26%), and 8+ = 72 (15%); T3b was 112 (23%); and T4 was 5 (1%). The median follow-up was 9.0 yr and, with MFS events reported for 89 participants (32 None, 31 Short, and 26 Long), there was no evidence of difference in MFS overall (logrank p = 0.98), and, for Long versus None, hazard ratio = 0.948 (95% confidence interval 0.54-1.68). After 10 yr, 80% None, 77% Short, and 81% Long patients were alive without metastatic disease. The three-way randomisation was not powered to conventional levels for assessment, yet provides a fair comparison.CONCLUSIONS AND CLINICAL IMPLICATIONS: Long-term outcomes after radical prostatectomy are usually favourable. In those indicated for postoperative RT and considered suitable for no, short-term, or long-term ADT, there was no evidence of improvement with addition of ADT. Future research should focus on patients at a higher risk of metastases in whom improvements are required more urgently.",

keywords = "Androgen deprivation therapy, Clinical trials, Duration, Hormone therapy, Multiarm trial, Prostate cancer, Radical prostatectomy, Radiotherapy, Randomised controlled trial",

author = "Parker, {Chris C} and Clarke, {Noel W} and Cook, {Adrian D} and Petersen, {Peter M} and Catton, {Charles N} and Cross, {William R} and Howard Kynaston and Persad, {Raj A} and Fred Saad and John Logue and Heather Payne and Claire Amos and Lorna Bower and Rakesh Raman and Ian Sayers and Jane Worlding and Parulekar, {Wendy R} and Parmar, {Mahesh K B} and Sydes, {Matthew R} and {RADICALS investigators}",

note = "Copyright {\textcopyright} 2024. Published by Elsevier B.V.",

year = "2024",

month = aug,

day = "30",

doi = "10.1016/j.eururo.2024.07.026",

language = "English",

journal = "European Urology",

issn = "0302-2838",

publisher = "Elsevier BV",

}

TY - JOUR

T1 - Randomised Trial of No, Short-term, or Long-term Androgen Deprivation Therapy with Postoperative Radiotherapy After Radical Prostatectomy

T2 - Results from the Three-way Comparison of RADICALS-HD (NCT00541047)

AU - Parker, Chris C

AU - Clarke, Noel W

AU - Cook, Adrian D

AU - Petersen, Peter M

AU - Catton, Charles N

AU - Cross, William R

AU - Kynaston, Howard

AU - Persad, Raj A

AU - Saad, Fred

AU - Logue, John

AU - Payne, Heather

AU - Amos, Claire

AU - Bower, Lorna

AU - Raman, Rakesh

AU - Sayers, Ian

AU - Worlding, Jane

AU - Parulekar, Wendy R

AU - Parmar, Mahesh K B

AU - Sydes, Matthew R

AU - RADICALS investigators

PY - 2024/8/30

Y1 - 2024/8/30

N2 - BACKGROUND AND OBJECTIVE: The use and duration of androgen deprivation therapy (ADT) with postoperative radiotherapy (RT) have been uncertain. RADICALS-HD compared adding no ("None"), 6-months ("Short"), or 24-mo ("Long") ADT to study efficacy in the long term.METHODS: Participants with prostate cancer were indicated for postoperative RT and agreed randomisation between all durations. ADT was allocated for 0, 6, or 24 mo. The primary outcome measure (OM) was metastasis-free survival (MFS). The secondary OMs included freedom from distant metastasis, overall survival, and initiation of nonprotocol ADT. Sample size was determined by two-way comparisons. Analyses followed standard time-to-event approaches and intention-to-treat principles.KEY FINDINGS AND LIMITATIONS: Between 2007 and 2015, 492 participants were randomised one of three groups: 166 None, 164 Short, and 162 Long. The median age at randomisation was 66 yr; Gleason scores at surgery were as follows: <7 = 64 (13%), 3+4 = 229 (47%), 4+3 = 127 (26%), and 8+ = 72 (15%); T3b was 112 (23%); and T4 was 5 (1%). The median follow-up was 9.0 yr and, with MFS events reported for 89 participants (32 None, 31 Short, and 26 Long), there was no evidence of difference in MFS overall (logrank p = 0.98), and, for Long versus None, hazard ratio = 0.948 (95% confidence interval 0.54-1.68). After 10 yr, 80% None, 77% Short, and 81% Long patients were alive without metastatic disease. The three-way randomisation was not powered to conventional levels for assessment, yet provides a fair comparison.CONCLUSIONS AND CLINICAL IMPLICATIONS: Long-term outcomes after radical prostatectomy are usually favourable. In those indicated for postoperative RT and considered suitable for no, short-term, or long-term ADT, there was no evidence of improvement with addition of ADT. Future research should focus on patients at a higher risk of metastases in whom improvements are required more urgently.

AB - BACKGROUND AND OBJECTIVE: The use and duration of androgen deprivation therapy (ADT) with postoperative radiotherapy (RT) have been uncertain. RADICALS-HD compared adding no ("None"), 6-months ("Short"), or 24-mo ("Long") ADT to study efficacy in the long term.METHODS: Participants with prostate cancer were indicated for postoperative RT and agreed randomisation between all durations. ADT was allocated for 0, 6, or 24 mo. The primary outcome measure (OM) was metastasis-free survival (MFS). The secondary OMs included freedom from distant metastasis, overall survival, and initiation of nonprotocol ADT. Sample size was determined by two-way comparisons. Analyses followed standard time-to-event approaches and intention-to-treat principles.KEY FINDINGS AND LIMITATIONS: Between 2007 and 2015, 492 participants were randomised one of three groups: 166 None, 164 Short, and 162 Long. The median age at randomisation was 66 yr; Gleason scores at surgery were as follows: <7 = 64 (13%), 3+4 = 229 (47%), 4+3 = 127 (26%), and 8+ = 72 (15%); T3b was 112 (23%); and T4 was 5 (1%). The median follow-up was 9.0 yr and, with MFS events reported for 89 participants (32 None, 31 Short, and 26 Long), there was no evidence of difference in MFS overall (logrank p = 0.98), and, for Long versus None, hazard ratio = 0.948 (95% confidence interval 0.54-1.68). After 10 yr, 80% None, 77% Short, and 81% Long patients were alive without metastatic disease. The three-way randomisation was not powered to conventional levels for assessment, yet provides a fair comparison.CONCLUSIONS AND CLINICAL IMPLICATIONS: Long-term outcomes after radical prostatectomy are usually favourable. In those indicated for postoperative RT and considered suitable for no, short-term, or long-term ADT, there was no evidence of improvement with addition of ADT. Future research should focus on patients at a higher risk of metastases in whom improvements are required more urgently.

KW - Androgen deprivation therapy

KW - Clinical trials

KW - Duration

KW - Hormone therapy

KW - Multiarm trial

KW - Prostate cancer

KW - Radical prostatectomy

KW - Radiotherapy

KW - Randomised controlled trial

UR - http://www.scopus.com/inward/record.url?scp=85202760955&partnerID=8YFLogxK

U2 - 10.1016/j.eururo.2024.07.026

DO - 10.1016/j.eururo.2024.07.026

M3 - Journal article

C2 - 39217077

SN - 0302-2838

JO - European Urology

JF - European Urology

ER -

Randomised Trial of No, Short-term, or Long-term Androgen Deprivation Therapy with Postoperative Radiotherapy After Radical Prostatectomy: Results from the Three-way Comparison of RADICALS-HD (NCT00541047)

Abstract

Keywords

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