Conventional versus hypofractionated high-dose intensity-modulated radiotherapy for prostate cancer: 5-year outcomes of the randomised, non-inferiority, phase 3 CHHiP trial.

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.

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.

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.

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.

Cancer Research UK, Department of Health, and the National Institute for Health Research Cancer Research Network.

The Lancet. Oncology. 2016 Jun 20 [Epub ahead of print]

David Dearnaley, Isabel Syndikus, Helen Mossop, Vincent Khoo, Alison Birtle, David Bloomfield, John Graham, Peter Kirkbride, John Logue, Zafar Malik, Julian Money-Kyrle, Joe M O'Sullivan, Miguel Panades, Chris Parker, Helen Patterson, Christopher Scrase, John Staffurth, Andrew Stockdale, Jean Tremlett, Margaret Bidmead, Helen Mayles, Olivia Naismith, Chris South, Annie Gao, Clare Cruickshank, Shama Hassan, Julia Pugh, Clare Griffin, Emma Hall, CHHiP Investigators

The Institute of Cancer Research, London, UK; Royal Marsden NHS Foundation Trust, London, UK. Electronic address: ., Clatterbridge Cancer Centre, Wirral, UK., The Institute of Cancer Research, London, UK., The Institute of Cancer Research, London, UK; Royal Marsden NHS Foundation Trust, London, UK., Rosemere Cancer Centre, Royal Preston Hospital, Preston, UK., Brighton and Sussex University Hospitals, Brighton, UK., Beacon Centre, Musgrove Park Hospital, Taunton, UK., Sheffield Teaching Hospitals Foundation Trust, Sheffield, UK., Christie Hospital, Manchester, UK., Clatterbridge Cancer Centre, Wirral, UK., Royal Surrey County Hospital, Guildford, UK., Queen's University Belfast, Belfast, UK., Lincoln County Hospital, Lincoln, UK., The Institute of Cancer Research, London, UK; Royal Marsden NHS Foundation Trust, London, UK., Addenbrooke's Hospital, Cambridge, UK., Ipswich Hospital, Ipswich, UK., Cardiff University/Velindre Cancer Centre, Cardiff, UK., University Hospital Coventry, Coventry, UK., Brighton and Sussex University Hospitals, Brighton, UK., Royal Marsden NHS Foundation Trust, London, UK., Clatterbridge Cancer Centre, Wirral, UK., Royal Marsden NHS Foundation Trust, London, UK., Royal Surrey County Hospital, Guildford, UK., The Institute of Cancer Research, London, UK; Royal Marsden NHS Foundation Trust, London, UK., The Institute of Cancer Research, London, UK., The Institute of Cancer Research, London, UK., The Institute of Cancer Research, London, UK., The Institute of Cancer Research, London, UK., The Institute of Cancer Research, London, UK.