dc.contributor.author | Parker, CC | |
dc.contributor.author | Kynaston, H | |
dc.contributor.author | Cook, AD | |
dc.contributor.author | Clarke, NW | |
dc.contributor.author | Catton, CN | |
dc.contributor.author | Cross, WR | |
dc.contributor.author | Petersen, PM | |
dc.contributor.author | Persad, RA | |
dc.contributor.author | Pugh, CA | |
dc.contributor.author | Saad, F | |
dc.contributor.author | Logue, J | |
dc.contributor.author | Payne, H | |
dc.contributor.author | Bower, LC | |
dc.contributor.author | Brawley, C | |
dc.contributor.author | Rauchenberger, M | |
dc.contributor.author | Barkati, M | |
dc.contributor.author | Bottomley, DM | |
dc.contributor.author | Brasso, K | |
dc.contributor.author | Chung, HT | |
dc.contributor.author | Chung, PWM | |
dc.contributor.author | Conroy, R | |
dc.contributor.author | Falconer, A | |
dc.contributor.author | Ford, V | |
dc.contributor.author | Goh, CL | |
dc.contributor.author | Heath, CM | |
dc.contributor.author | James, ND | |
dc.contributor.author | Kim-Sing, C | |
dc.contributor.author | Kodavatiganti, R | |
dc.contributor.author | Malone, SC | |
dc.contributor.author | Morris, SL | |
dc.contributor.author | Nabid, A | |
dc.contributor.author | Ong, AD | |
dc.contributor.author | Raman, R | |
dc.contributor.author | Rodda, S | |
dc.contributor.author | Wells, P | |
dc.contributor.author | Worlding, J | |
dc.contributor.author | Parulekar, WR | |
dc.contributor.author | Parmar, MKB | |
dc.contributor.author | Sydes, MR | |
dc.contributor.author | RADICALS investigators, | |
dc.coverage.spatial | England | |
dc.date.accessioned | 2024-08-13T13:49:22Z | |
dc.date.available | 2024-08-13T13:49:22Z | |
dc.date.issued | 2024-06-01 | |
dc.identifier | S0140-6736(24)00549-X | |
dc.identifier.citation | The Lancet, 2024, 403 (10442), pp. 2416 - 2425 | |
dc.identifier.issn | 0140-6736 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/6357 | |
dc.identifier.eissn | 1474-547X | |
dc.identifier.eissn | 1474-547X | |
dc.identifier.doi | 10.1016/S0140-6736(24)00549-X | |
dc.identifier.doi | 10.1016/S0140-6736(24)00549-X | |
dc.description.abstract | BACKGROUND: 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. METHODS: 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. FINDINGS: 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. INTERPRETATION: 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. FUNDING: Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society. | |
dc.format | Print-Electronic | |
dc.format.extent | 2416 - 2425 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | Elsevier BV | |
dc.relation.ispartof | The Lancet | |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | |
dc.subject | Humans | |
dc.subject | Male | |
dc.subject | Prostatic Neoplasms | |
dc.subject | Androgen Antagonists | |
dc.subject | Prostatectomy | |
dc.subject | Aged | |
dc.subject | Tosyl Compounds | |
dc.subject | Middle Aged | |
dc.subject | Anilides | |
dc.subject | Nitriles | |
dc.subject | Oligopeptides | |
dc.subject | Gonadotropin-Releasing Hormone | |
dc.subject | Prostate-Specific Antigen | |
dc.subject | Combined Modality Therapy | |
dc.subject | Drug Administration Schedule | |
dc.title | 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. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2024-03-15 | |
dc.date.updated | 2024-08-13T13:48:41Z | |
rioxxterms.version | VoR | |
rioxxterms.versionofrecord | 10.1016/S0140-6736(24)00549-X | |
rioxxterms.licenseref.startdate | 2024-06-01 | |
rioxxterms.type | Journal Article/Review | |
pubs.author-url | https://www.ncbi.nlm.nih.gov/pubmed/38763153 | |
pubs.issue | 10442 | |
pubs.organisational-group | ICR | |
pubs.organisational-group | ICR/Primary Group | |
pubs.organisational-group | ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging | |
pubs.organisational-group | ICR/Primary Group/Royal Marsden Clinical Units | |
pubs.organisational-group | ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Prostate and Bladder Cancer Research | |
pubs.organisational-group | ICR/ImmNet | |
pubs.publication-status | Published | |
pubs.publisher-url | http://dx.doi.org/10.1016/s0140-6736(24)00549-x | |
pubs.volume | 403 | |
icr.researchteam | Prostate & Bladder Cancer | |
dc.contributor.icrauthor | James, Nicholas | |
icr.provenance | Deposited by Mr Arek Surman on 2024-08-13. Deposit type is initial. No. of files: 1. Files: 1-s2.0-S014067362400549X-main.pdf | |