Journal article
Adding 6 months of androgen deprivation therapy to postoperative radiotherapy for prostate cancer: a comparison of short-course versus no androgen deprivation therapy in the RADICALS-HD randomised controlled trial
The Lancet (British edition), Vol.403(10442), pp.2405-2415
06/01/2024
DOI: 10.1016/S0140-6736(24)00548-8
PMCID: PMC7616360
PMID: 38763154
Abstract
Previous evidence indicates that adjuvant, short-course androgen deprivation therapy (ADT) improves metastasis-free survival when given with primary radiotherapy for intermediate-risk and high-risk localised prostate cancer. However, the value of ADT with postoperative radiotherapy after radical prostatectomy is unclear.
RADICALS-HD was an international randomised controlled trial to test the efficacy of ADT used in combination with postoperative radiotherapy for prostate cancer. Key eligibility criteria were indication for radiotherapy after radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to radiotherapy alone (no ADT) or radiotherapy with 6 months of ADT (short-course ADT), using monthly subcutaneous gonadotropin-releasing hormone analogue injections, daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as distant metastasis arising from prostate cancer or death from any cause. Standard survival analysis methods were used, accounting for randomisation stratification factors. The trial had 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 80% to 86% (hazard ratio [HR] 0·67). Analyses followed the intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov, NCT00541047.
Between Nov 22, 2007, and June 29, 2015, 1480 patients (median age 66 years [IQR 61-69]) were randomly assigned to receive no ADT (n=737) or short-course ADT (n=743) in addition to postoperative radiotherapy at 121 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 9·0 years (IQR 7·1-10·1), metastasis-free survival events were reported for 268 participants (142 in the no ADT group and 126 in the short-course ADT group; HR 0·886 [95% CI 0·688-1·140], p=0·35). 10-year metastasis-free survival was 79·2% (95% CI 75·4-82·5) in the no ADT group and 80·4% (76·6-83·6) in the short-course ADT group. Toxicity of grade 3 or higher was reported for 121 (17%) of 737 participants in the no ADT group and 100 (14%) of 743 in the short-course ADT group (p=0·15), with no treatment-related deaths.
Metastatic disease is uncommon following postoperative bed radiotherapy after radical prostatectomy. Adding 6 months of ADT to this radiotherapy did not improve metastasis-free survival compared with no ADT. These findings do not support the use of short-course ADT with postoperative radiotherapy in this patient population.
Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society.
Details
- Title: Subtitle
- Adding 6 months of androgen deprivation therapy to postoperative radiotherapy for prostate cancer: a comparison of short-course versus no androgen deprivation therapy in the RADICALS-HD randomised controlled trial
- Creators
- Chris C Parker - Royal Marsden NHS Foundation TrustNoel W Clarke - Cancer Research UK Manchester InstituteAdrian D Cook - MRC Clinical Trials Unit at UCLHoward Kynaston - Cardiff UniversityCharles N Catton - Princess Margaret Cancer CentreWilliam R Cross - St James's University HospitalPeter M Petersen - Cancer Research UK Manchester InstituteRajendra A Persad - Department of Urology, Bristol Urological Institute, Bristol, UKFred Saad - Centre Hospitalier de l’Université de MontréalLorna C Bower - Institute of Cancer ResearchJohn Logue - The Christie NHS Foundation TrustHeather Payne - The Prostate CentreSilvia Forcat - MRC Clinical Trials Unit at UCLCindy Goldstein - MRC Clinical Trials Unit at UCLClaire Murphy - MRC Clinical Trials Unit at UCLJuliette Anderson - St James's University HospitalMaroie Barkati - Centre Hospitalier de l’Université de MontréalDavid M Bottomley - St James's University HospitalJennifer Branagan - Northampton General HospitalAnanya Choudhury - Cancer Research UK Manchester InstitutePeter W M ChungLyn Cogley - Derriford HospitalChee L Goh - Royal Surrey County HospitalPeter Hoskin - Cancer Research UK Manchester InstituteVincent Khoo - Royal Marsden NHS Foundation TrustShawn C Malone - University of OttawaLindsey Masters - MRC Clinical Trials Unit at UCLStephen L Morris - Guy's and St Thomas' NHS Foundation TrustAbdenour Nabid - Centre Hospitalier Universitaire de SherbrookeAldrich D Ong - University of ManitobaRakesh Raman - Kent and Canterbury HospitalKathryn L Tarver - Queen's HospitalAlison C Tree - Royal Marsden NHS Foundation TrustJane Worlding - University Hospitals Coventry and Warwickshire NHS TrustJames P Wylie - The Christie NHS Foundation TrustAnjali M Zarkar - NIHR Surgical Reconstruction and Microbiology Research CentreWendy R Parulekar - Queen's UniversityMahesh K B Parmar - University College LondonMatthew R Sydes - MRC Clinical Trials Unit at UCLRADICALS investigatorsSara C Horton - Stead Family Department of Pediatrics
- Resource Type
- Journal article
- Publication Details
- The Lancet (British edition), Vol.403(10442), pp.2405-2415
- DOI
- 10.1016/S0140-6736(24)00548-8
- PMID
- 38763154
- PMCID
- PMC7616360
- ISSN
- 0140-6736
- eISSN
- 1474-547X
- Language
- English
- Date published
- 06/01/2024
- Academic Unit
- Stead Family Department of Pediatrics; Hematology/Oncology
- Record Identifier
- 9984701643402771
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