Journal article
Duration of androgen deprivation therapy with postoperative radiotherapy for prostate cancer: a comparison of long-course versus short-course androgen deprivation therapy in the RADICALS-HD randomised trial
The Lancet (British edition), Vol.403(10442), pp.2416-2425
06/01/2024
DOI: 10.1016/S0140-6736(24)00549-X
PMCID: PMC7616389
PMID: 38763153
Abstract
Previous evidence supports androgen deprivation therapy (ADT) with primary radiotherapy as initial treatment for intermediate-risk and high-risk localised prostate cancer. However, the use and optimal duration of ADT with postoperative radiotherapy after radical prostatectomy remains uncertain.
RADICALS-HD was a randomised controlled trial of ADT duration within the RADICALS protocol. Here, we report on the comparison of short-course versus long-course ADT. Key eligibility criteria were indication for radiotherapy after previous 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 add 6 months of ADT (short-course ADT) or 24 months of ADT (long-course ADT) to radiotherapy, using subcutaneous gonadotrophin-releasing hormone analogue (monthly in the short-course ADT group and 3-monthly in the long-course ADT group), 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 metastasis arising from prostate cancer or death from any cause. The comparison had more than 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 75% to 81% (hazard ratio [HR] 0·72). Standard time-to-event analyses were used. Analyses followed intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov, NCT00541047.
Between Jan 30, 2008, and July 7, 2015, 1523 patients (median age 65 years, IQR 60-69) were randomly assigned to receive short-course ADT (n=761) or long-course ADT (n=762) in addition to postoperative radiotherapy at 138 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 8·9 years (7·0-10·0), 313 metastasis-free survival events were reported overall (174 in the short-course ADT group and 139 in the long-course ADT group; HR 0·773 [95% CI 0·612-0·975]; p=0·029). 10-year metastasis-free survival was 71·9% (95% CI 67·6-75·7) in the short-course ADT group and 78·1% (74·2-81·5) in the long-course ADT group. Toxicity of grade 3 or higher was reported for 105 (14%) of 753 participants in the short-course ADT group and 142 (19%) of 757 participants in the long-course ADT group (p=0·025), with no treatment-related deaths.
Compared with adding 6 months of ADT, adding 24 months of ADT improved metastasis-free survival in people receiving postoperative radiotherapy. For individuals who can accept the additional duration of adverse effects, long-course ADT should be offered with postoperative radiotherapy.
Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society.
Details
- Title: Subtitle
- Duration of androgen deprivation therapy with postoperative radiotherapy for prostate cancer: a comparison of long-course versus short-course androgen deprivation therapy in the RADICALS-HD randomised trial
- Creators
- Chris C Parker - Royal Marsden NHS Foundation TrustHoward Kynaston - Cardiff UniversityAdrian D Cook - University College LondonNoel W Clarke - Salford Royal NHS Foundation TrustCharles N Catton - Princess Margaret Cancer CentreWilliam R Cross - St James's University HospitalPeter M Petersen - University of CopenhagenRajendra A Persad - Department of Urology, Bristol Urological Institute, Bristol, UKCheryl A Pugh - University College LondonFred Saad - Centre Hospitalier de l’Université de MontréalJohn Logue - The Christie NHS Foundation TrustHeather Payne - The Prostate CentreLorna C Bower - Institute of Cancer ResearchChris Brawley - University College LondonMary Rauchenberger - University College LondonMaroie Barkati - Centre Hospitalier de l’Université de MontréalDavid M Bottomley - St James's University HospitalKlaus Brasso - RigshospitaletRuth Conroy - The Christie NHS Foundation TrustHans T Chung - University of TorontoAlison Falconer - Charing Cross HospitalPeter W M ChungVicky Ford - Phillips Exeter AcademyChee L Goh - Royal Surrey County HospitalCatherine M Heath - University Hospital Southampton NHS Foundation TrustNicholas D James - Institute of Cancer ResearchCharmaine Kim-Sing - Department of Radiation Oncology, BC Cancer-Vancouver, Vancouver, BC, CanadaRavi Kodavatiganti - Glan Clwyd HospitalShawn C Malone - University of OttawaStephen 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 HospitalSree Rodda - Bradford Teaching Hospitals NHS Foundation TrustPaula Wells - St Bartholomew's HospitalJane Worlding - University Hospitals Coventry and Warwickshire NHS TrustWendy R Parulekar - Queen's UniversityMahesh K B Parmar - University College LondonMatthew R Sydes - University College LondonRADICALS investigatorsSara C Horton - Stead Family Department of Pediatrics
- Resource Type
- Journal article
- Publication Details
- The Lancet (British edition), Vol.403(10442), pp.2416-2425
- Publisher
- ELSEVIER SCIENCE INC; NEW YORK
- DOI
- 10.1016/S0140-6736(24)00549-X
- PMID
- 38763153
- PMCID
- PMC7616389
- ISSN
- 0140-6736
- eISSN
- 1474-547X
- Grant note
Cancer Research UK, UK Research and Innovation (formerly Medical Research Council) , and Canadian Cancer Society.
- Language
- English
- Date published
- 06/01/2024
- Academic Unit
- Stead Family Department of Pediatrics; Hematology/Oncology
- Record Identifier
- 9984701550402771
Metrics
5 Record Views