5 year outcomes of a phase III randomised trial of conventional or hypofractionated high dose intensity modulated radiotherapy for prostate cancer [CRUK/06/016]: report from the CHHiP Trial Management Group

Emma Hall1,Isabel Syndikus2,Helen Mossop1,John Staffurth3,Christopher Scrase4,Miguel Panades5,Julian Money-Kyrle6,John Logue7,Vincent Khoo8,John Graham9,David Bloomfield10,Alison Birtle11,Jean Tremlett10,Olivia Naismith8,Helen Mayles2,Shama Hassan1,Clare Cruickshank1,Clare Griffin1,David Dearnaley1,8

1The Institute of Cancer Research, London, UK,2Clatterbridge Cancer Centre, Wirral, UK,3Velindre Cancer Centre, Cardiff, UK,4Ipswich Hospital, Ipswich, UK,5Lincoln County Hospital, Lincoln, UK,6Royal Surrey County Hospital, Guildford, UK,7Christie Hospital, Manchester, UK,8Royal Marsden NHS Trust, London, UK,9Musgrove Park Hospital, Taunton, UK,10Royal Sussex County Hospital, Brighton, UK,11Royal Preston Hospital, Preston, UK

Presenting date: Wednesday 4 November

Background

CHHiP is a non-inferiority trial to determine efficacy and safety of hypofractionated radiotherapy (hRT) using intensity modulated radiotherapy.

Method

Patients with node negative T1b-T3a localised prostate cancer (PCa) were randomised (1:1:1 ratio) to 74 Gray(Gy)/37 fractions(f) (control), 60Gy/20f or 57Gy/19f. The primary endpoint was PCa progression, defined as freedom from biochemical failure (Phoenix consensus guidelines) or PCa recurrence. 3213 patients were needed to rule out 5% inferiority (80% power, one-sided alpha 5%) assuming 70% event-free in the control arm (critical hazard ratio (HR): 1.208). Toxicity was assessed to week 18 post start of RT and late side effects 6 monthly to 2 years (yr) and yearly to 5yr by RTOG, LENT-SOM and patient reported outcomes (PROs).

Results

3216 patients were randomised between 2002 and 2011. Baseline characteristics were well balanced: median age 69yr; PSA 10.1ng/ml; NCCN risk group 15% low, 73% intermediate, 12% high. With median follow up of 62 months, 5yr progression-free rate (95%CI) was 74Gy: 88.3% (86.0%, 90.2%); 60Gy: 90.6% (88.5%, 92.3%), 57Gy: 85.9 (83.4, 88.0); HR60: 0.83, 90%CI (0.68, 1.03), HR57: 1.20, 90%CI (0.99, 1.45). Acute RTOG grade 2+ (G2+) bowel toxicity was higher in patients receiving hRT, with no significant difference in G2+ bladder toxicity. Late toxicity profile was favourable with significantly less RTOG G2+ bowel toxicity observed with 57Gy compared to 74Gy at 2yr, but no significant difference at 5yr. G2+ bladder toxicity showed no significant difference between control and experimental groups at 2yr or 5yr. Analysis of LENT-SOM and PROs supported these results.

Conclusion

After 5yr follow up, 60Gy/20f is non-inferior to control for PCa progression and is not associated with significant differences in late toxicity. 57Gy/19f has not been shown to be non-inferior. hRT using 60Gy/20f appears effective and safe and may be recommended as a new standard of care.