Conventional versus hypofractionated high-dose intensity-modulated radiotherapy for prostate cancer: 5-year outcomes of the randomised, non-inferiority, phase 3 CHHiP trial
Open accessAbstract
BACKGROUND: Prostate cancer might have high radiation-fraction sensitivity that would give a therapeutic advantage to hypofractionated treatment. We present a pre-planned analysis of the efficacy and side-effects of a randomised trial comparing conventional and hypofractionated radiotherapy after 5 years follow-up. METHODS: CHHiP is a randomised, phase 3, non-inferiority trial that recruited men with localised prostate cancer (pT1b-T3aN0M0). Patients were randomly assigned (1:1:1) to conventional (74 Gy delivered in 37 fractions over 7·4 weeks) or one of two hypofractionated schedules (60 Gy in 20 fractions over 4 weeks or 57 Gy in 19 fractions over 3·8 weeks) all delivered with intensity-modulated techniques. Most patients were given radiotherapy with 3-6 months of neoadjuvant and concurrent androgen suppression. Randomisation was by computer-generated random permuted blocks, stratified by National Comprehensive Cancer Network (NCCN) risk group and radiotherapy treatment centre, and treatment allocation was not masked. The primary endpoint was time to biochemical or clinical failure; the critical hazard ratio (HR) for non-inferiority was 1·208. Analysis was by intention to treat. Long-term follow-up continues. The CHHiP trial is registered as an International Standard Randomised Controlled Trial, number ISRCTN97182923. FINDINGS: Between Oct 18, 2002, and June 17, 2011, 3216 men were enrolled from 71 centres and randomly assigned (74 Gy group, 1065 patients; 60 Gy group, 1074 patients; 57 Gy group, 1077 patients). Median follow-up was 62·4 months (IQR 53·9-77·0). The proportion of patients who were biochemical or clinical failure free at 5 years was 88·3% (95% CI 86·0-90·2) in the 74 Gy group, 90·6% (88·5-92·3) in the 60 Gy group, and 85·9% (83·4-88·0) in the 57 Gy group. 60 Gy was non-inferior to 74 Gy (HR 0·84 [90% CI 0·68-1·03], pNI=0·0018) but non-inferiority could not be claimed for 57 Gy compared with 74 Gy (HR 1·20 [0·99-1·46], pNI=0·48). Long-term side-effects were similar in the hypofractionated groups compared with the conventional group. There were no significant differences in either the proportion or cumulative incidence of side-effects 5 years after treatment using three clinician-reported as well as patient-reported outcome measures. The estimated cumulative 5 year incidence of Radiation Therapy Oncology Group (RTOG) grade 2 or worse bowel and bladder adverse events was 13·7% (111 events) and 9·1% (66 events) in the 74 Gy group, 11·9% (105 events) and 11·7% (88 events) in the 60 Gy group, 11·3% (95 events) and 6·6% (57 events) in the 57 Gy group, respectively. No treatment-related deaths were reported. INTERPRETATION: Hypofractionated radiotherapy using 60 Gy in 20 fractions is non-inferior to conventional fractionation using 74 Gy in 37 fractions and is recommended as a new standard of care for external-beam radiotherapy of localised prostate cancer. FUNDING: Cancer Research UK, Department of Health, and the National Institute for Health Research Cancer Research Network.
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Primary endocrine therapy for older patients with early-stage ER-positive, HER2-negative breast cancer is supported by evidence showing no positive impact of surgery on overall survival.
“For example, the use of primary endocrine therapy for older patients with early-stage ER-positive, HER2-negative breast cancer is supported by evidence demonstrating no positive impact of surgery on overall survival (OS) [[48], [49], [50]].”
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Cites
Cox, J. D., Stetz, J., & Pajak, T. F. (1995) · International Journal of Radiation Oncology*Biology*Physics · doi:10.1016/0360-3016(95)00060-c · Cited by 4,811 · see citing works
Roach, M., Hanks, G. E., Thames, H. D., Schellhammer, P. F., Shipley, W. U., Sokol, G. H., & Sandler, H. M. (2006) · International Journal of Radiation Oncology*Biology*Physics · doi:10.1016/j.ijrobp.2006.04.029 · Cited by 2,751 · see citing works
Brenner, D. J., Martinez, A. A., Edmundson, G. K., Mitchell, C. K., Thames, H. D., & Armour, E. P. (2002) · International Journal of Radiation Oncology*Biology*Physics · doi:10.1016/s0360-3016(01)02664-5 · Cited by 650 · see citing works
Is α/β for prostate tumors really low?
Fowler, J., Chappell, R. J., & Ritter, M. A. (2001) · International Journal of Radiation Oncology*Biology*Physics · doi:10.1016/s0360-3016(01)01607-8 · Cited by 631 · see citing works
Soerjomataram, I., Lortet‐Tieulent, J., Parkin, D. M., Ferlay, J., Mathers, C. D., Forman, D., & Bray, F. (2012) · The Lancet · doi:10.1016/s0140-6736(12)60919-2 · Cited by 598 · see citing works
Miralbell, R., Roberts, S. A., Zubizarreta, E., et al. (2011) · International Journal of Radiation Oncology*Biology*Physics · doi:10.1016/j.ijrobp.2010.10.075 · Cited by 527 · see citing works
Randomized Trial of Hypofractionated External-Beam Radiotherapy for Prostate Cancer
Pollack, A. S., Walker, G. R., Horwitz, E. M., Price, R., Feigenberg, S. J., Konski, A. A., Stoyanova, R. S., Movsas, B., Greenberg, R. E., Uzzo, R. G., et al. (2013) · Journal of Clinical Oncology · doi:10.1200/jco.2013.51.1972 · Cited by 467 · see citing works
Roach, M., Marquez, C., Yuo, H. S., et al. (1994) · International Journal of Radiation Oncology*Biology*Physics · doi:10.1016/0360-3016(94)90138-4 · Cited by 464 · see citing works
Dearnaley, D. P., Jovic, G., Syndikus, I., Khoo, V. S., Cowan, R. A., Graham, J. D., Aird, E. G. A., Bottomley, D., Huddart, R. A., Jose, C. C., et al. (2014) · The Lancet Oncology · doi:10.1016/s1470-2045(14)70040-3 · Cited by 463 · see citing works
Self-citationTime-dose factors in radiotherapy: a review of the human data
Thames, H. D., Bentzen, S. M., Turesson, I., et al. (1990) · Radiotherapy and Oncology · doi:10.1016/0167-8140(90)90149-q · Cited by 409 · see citing works
Aluwini, S., Pos, F. J., Schimmel, E. C., et al. (2016) · The Lancet Oncology · doi:10.1016/s1470-2045(15)00567-7 · Cited by 319 · see citing works
Dearnaley, D. P., Syndikus, I., Sumo, G., et al. (2011) · The Lancet Oncology · doi:10.1016/s1470-2045(11)70293-5 · Cited by 310 · see citing works
Self-citationLENT SOMA tables table of contents
(1995) · Radiotherapy and Oncology · doi:10.1016/0167-8140(95)90055-1 · Cited by 289 · see citing works
Prostate alpha/beta revisited – an analysis of clinical results from 14 168 patients
Daşu, A., & Toma-Daşu, I. (2012) · Acta Oncologica · doi:10.3109/0284186x.2012.719635 · Cited by 234 · see citing works
Vogelius, I. R., & Bentzen, S. M. (2012) · International Journal of Radiation Oncology*Biology*Physics · doi:10.1016/j.ijrobp.2012.03.004 · Cited by 202 · see citing works
Aluwini, S., Pos, F. J., Schimmel, E. C., van Lin, E. N. J. T., Krol, A. D. G., van der Toorn, P. P., de Jager, H., Dirkx, M. L. P., Alemayehu, W. G., Heijmen, B. J. M., et al. (2015) · The Lancet Oncology · doi:10.1016/s1470-2045(14)70482-6 · Cited by 186 · see citing works
Arcangeli, G., Fowler, J., Gomellini, S., et al. (2010) · International Journal of Radiation Oncology*Biology*Physics · doi:10.1016/j.ijrobp.2009.12.045 · Cited by 159 · see citing works
Proust‐Lima, C., Taylor, J. M. G., Sécher, S., et al. (2010) · International Journal of Radiation Oncology*Biology*Physics · doi:10.1016/j.ijrobp.2009.10.008 · Cited by 156 · see citing works
Wilkins, A. C., Mossop, H., Syndikus, I., Khoo, V. S., Bloomfield, D. J., Parker, C. C., Logue, J. P., Scrase, C. D., Patterson, H., Birtle, A. J., et al. (2015) · The Lancet Oncology · doi:10.1016/s1470-2045(15)00280-6 · Cited by 149 · see citing works
Self-citationHoffman, K. E., Voong, K. R., Pugh, T. J., et al. (2014) · International Journal of Radiation Oncology*Biology*Physics · doi:10.1016/j.ijrobp.2014.01.015 · Cited by 133 · see citing works
Pedicini, P., Caivano, R., Strigari, L., et al. (2012) · International Journal of Radiation Oncology*Biology*Physics · doi:10.1016/j.ijrobp.2012.03.056 · Cited by 127 · see citing works
Zaorsky, N. G., Palmer, J. D., Hurwitz, M., et al. (2015) · Radiotherapy and Oncology · doi:10.1016/j.radonc.2015.05.011 · Cited by 118 · see citing works
Diaz, A. Z., Roach, M., Marquez, C., et al. (1994) · International Journal of Radiation Oncology*Biology*Physics · doi:10.1016/0360-3016(94)90011-6 · Cited by 116 · see citing works
A Systematic Review of Hypofractionation for Primary Management of Prostate Cancer
Koontz, B. F., Bossi, A., Cozzarini, C., et al. (2014) · European Urology · doi:10.1016/j.eururo.2014.08.009 · Cited by 103 · see citing works
A systematic review of randomised controlled trials of radiotherapy for localised prostate cancer
Wolff, R. F., Ryder, S., Bossi, A., Briganti, A., Crook, J. M., Henry, A. M., Karnes, J. R., Potters, L., de Reijke, T. M., Stone, N. N., et al. (2015) · European Journal of Cancer · doi:10.1016/j.ejca.2015.07.019 · Cited by 95 · see citing works
(1995) · PubMed · Cited by 91 · see citing works
Syndikus, I., Morgan, R. C., Sydes, M. R., Graham, J. D., & Dearnaley, D. P. (2009) · International Journal of Radiation Oncology*Biology*Physics · doi:10.1016/j.ijrobp.2009.05.052 · Cited by 90 · see citing works
Self-citationDearnaley, D. P., Sydes, M. R., Langley, R. E., Graham, J. D., Huddart, R. A., Syndikus, I., Matthews, J. H. L., Scrase, C. D., Jose, C. C., Logue, J. P., et al. (2007) · Radiotherapy and Oncology · doi:10.1016/j.radonc.2007.02.014 · Cited by 80 · see citing works
Self-citationNorkus, D., Karklelyte, A., Engels, B., et al. (2013) · Radiation Oncology · doi:10.1186/1748-717x-8-206 · Cited by 61 · see citing works
Systematic review of hypofractionated radiation therapy for prostate cancer
Zaorsky, N. G., Ohri, N., Showalter, T. N., et al. (2013) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2013.01.008 · Cited by 60 · see citing works
Khoo, V. S., & Dearnaley, D. P. (2007) · Clinical Oncology · doi:10.1016/j.clon.2007.10.008 · Cited by 59 · see citing works
Self-citationHou, Z., Li, G., & Bai, S. (2014) · Journal of Cancer Research and Clinical Oncology · doi:10.1007/s00432-014-1813-1 · Cited by 55 · see citing works
Radiotherapy Demand and Activity in England 2006–2020
Round, C., Williams, M. V., Mee, T., et al. (2013) · Clinical Oncology · doi:10.1016/j.clon.2013.05.005 · Cited by 49 · see citing works
South, C., Khoo, V. S., Naismith, O. F., et al. (2007) · Clinical Oncology · doi:10.1016/j.clon.2007.10.012 · Cited by 43 · see citing works
Self-citationTree, A., Alexander, E. J., van As, N. J., et al. (2013) · Clinical Oncology · doi:10.1016/j.clon.2013.05.003 · Cited by 41 · see citing works
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Battisti, N. M. L., Mislang, A. R., Cooper, L., O'Donovan, A., Audisio, R. A., Cheung, K.-L., Sarrió, R. G., Stauder, R., Soto-Perez-de-Celis, E., Jaklitsch, M., et al. (2020) · Journal of Geriatric Oncology · doi:10.1016/j.jgo.2020.07.008 · Cited by 79 · see citing works
- Authors
- Dearnaley, D., Syndikus, I., Mossop, H., Khoo, V., Birtle, A., Bloomfield, D., Graham, J., Kirkbride, P., Logue, J., Malik, Z., Money-Kyrle, J., O'Sullivan, J. M., Panades, M., Parker, C., Patterson, H., Scrase, C., Staffurth, J., Stockdale, A., Tremlett, J., Bidmead, M., Mayles, H., Naismith, O., South, C., Gao, A., Cruickshank, C., Hassan, S., Pugh, J., Griffin, C., & Hall, E.
- Affiliations
- Royal Marsden NHS Foundation Trust (GB)
- Clatterbridge Cancer Centre NHS Foundation Trust (GB)
- Institute of Cancer Research (GB)
- Royal Preston Hospital (GB)
- Musgrove Park Hospital (GB)
- Sheffield Teaching Hospitals NHS Foundation Trust (GB)
- The Christie Hospital (GB)
- Lincoln County Hospital (GB)
- Addenbrooke's Hospital (GB)
- Ipswich Hospital (GB)
- Velindre Cancer Centre (GB)
- University Hospital Coventry (GB)
- Royal Surrey County Hospital (GB)
- Corresponding author
- Dearnaley, David
- ORCID
- Venue
- The Lancet Oncology
- Publisher
- Elsevier BV
- Published
- 2016-08
- Volume
- 17
- Issue
- 8
- Pages
- 1047-1060
- ISSN
- 1470-2045 (ISSN-L)
- PMC
- PMC4961874
- OpenAlex
- W2465092116
- Cited by
- 1,339
- References
- 35
- Citations by year
- 2026: 99 · 2025: 146 · 2024: 132 · 2023: 145 · 2022: 146 · 2021: 152 · 2020: 158 · 2019: 143 · 2018: 106 · 2017: 80 · 2016: 30
- FWCI
- 107.05
- Type
- journal article
- Language
- en
- Update notices
- erratum (2016-08-01)
- Open access
- hybrid
- doi.org
- Licence
- Locations
- The Lancet Oncology (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- ORCA Online Research @Cardiff (Cardiff University) (acceptedVersion)
- Research Portal (Queen's University Belfast) (submittedVersion, cc-by)
- Minerva Access (University of Melbourne) (submittedVersion, cc-by)
- Newcastle University ePrints (Newcastle Univesity)
- Funders
- Health Research Board (ICORG-2016-1)
- Cancer Research UK (12518, 19727, 10588)
- National Institute for Health and Care Research (NF-SI-0611-10106)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Prostate Cancer Diagnosis and Treatment
- Physical Sciences › Physics and Astronomy › Radiation › Advanced Radiotherapy Techniques
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Breast Cancer Treatment Studies
- Keywords
- prostate cancer, hypofractionated radiotherapy, intensity-modulated radiotherapy, high-dose radiotherapy, conventional fractionation, non-inferiority, biochemical recurrence, clinical failure, androgen deprivation therapy, neoadjuvant therapy, long-term outcomes, radiation toxicity, late effects, quality of life, NCCN risk classification
- MeSH terms
- Radiation Dose Hypofractionation, Aged, Aged, 80 and over, Follow-Up Studies, Humans, International Agencies, Male, Middle Aged, Neoplasm Staging, Prostatic Neoplasms, Risk Factors, Survival Rate, Treatment Outcome, Radiotherapy, Intensity-Modulated
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