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

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 pro...

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Published in:The Lancet (British edition) 2024-06, Vol.403 (10442), p.2405-2415
Main Authors: Hoskin, Peter, Herasimtschuk, Anna, Pickering, Holly, Rauchenberger, Mary, Brown, Teddy, Smith, Margaret, Coventry, Thomas, Ford, Victoria, Krysta, Beata, Robertson, Bryony, Cousins, Jane, Zarkar, Anjali, Kedge, Liz, Flavin, Aileen, Metcalf, Karen, Teo, Mark, Hollister, Robert, Wheeler, Lucie, Brain, Carol, Treasure, Ann, Mazhar, Danish, Ramanujachar, Ramya, Appleby, Bonny, Galante, Joao, Skelton, Amy, Martindale, John, Penhaligon, Corrine, Javle, P, Taylor, Jennifer, Forman, Susan, Roantree, Alison, Stone, Sarah, Hughes, Robert, Stapleton, Stephanie, Brown, Sandra, Doughty, Victoria, Lister, Debbie, Young, Sally, Bermingham, Nicola, Sadare (Olaleye), Ibiyemi, Balogun, Shaki, Hijab, Adham, Nawrozzadeh, Mohammed, Patel, Priyanka, Thomson, Sister Jane, Kuenzig, Greg, Neave, Farhad, Storrs, Sarah, Riches, Oscar, Agdiran, Didem, Mitra, Anita, Collins, Gerald, Hardstaff, Lisa, Choudhury, Ananya, Partington, Lillian, Birch, Richard, London, Clare, Hodson, Hayley, Lydon, Anne Marie, Wadsworth, Oliver, Campbell, Allister, Dallas, Nicola, Darch, Flora, Mahoney, Sue, Corcoran, Sam, Johnstone, Maria, Taylor, Becky, Millage, Helen, Bowling, Lorna, Fallah, Fereshteh, Harvey, Sally, Holbrook, Andy, Raftery, Liz, Moller Christensen, Trine, Pokhrel, Sujata, Lavertu, Sophie, Trudel, Diane, Murtha, Albert, Dugas, Stevie, Moffatt, Emily, Dayes, Ian S, Creelman, Brianna, Opitz, Debbie, Edwards, Jackie, Shantz, Brenda S, Eichenberger, Lois, Mayer, Heather, Lachance, Nicole, Albrecht, Virginia, Singson, Angelina, Somasiri, Ashane, Haddad, Alain, Pochini, Craig, Danjoux, Cyril, Escueta, Vivette, Leung, Michael, Tseng, Eric Chia Lin, Muraj, Zaynab, Nichol, Rhonda, Rudnicki, Rayleen
Format: Article
Language:English
Subjects:
Aged
Androgen Antagonists - administration & dosage
Androgen Antagonists - therapeutic use
Androgens
Anilides - administration & dosage
Anilides - therapeutic use
Antigens
Cancer therapies
Clinical medicine
Combined Modality Therapy
Deprivation
Gonadotropin-releasing hormone
Gonadotropin-Releasing Hormone - agonists
Gonadotropins
Health services
Humans
Male
Medical innovations
Medical research
Metastases
Metastasis
Middle Aged
Nitriles - administration & dosage
Nitriles - therapeutic use
Oligopeptides - administration & dosage
Oligopeptides - therapeutic use
Oncology
Patients
Pituitary (anterior)
Prostate cancer
Prostate-specific antigen
Prostate-Specific Antigen - blood
Prostatectomy
Prostatic Neoplasms - drug therapy
Prostatic Neoplasms - pathology
Prostatic Neoplasms - radiotherapy
Prostatic Neoplasms - therapy
Radiation therapy
Randomization
Survival
Tosyl Compounds - administration & dosage
Tosyl Compounds - therapeutic use
Toxicity
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Summary: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 t
ISSN:0140-6736
1474-547X
1474-547X
DOI:10.1016/S0140-6736(24)00548-8