Background
Phase III RCT (CHHiP — Conventional or Hypofractionated High-dose Intensity Modulated Radiotherapy for Prostate Cancer). 3,216 men with localized prostate cancer (pT1b–T3aN0M0), enrolled 2002–2011 at 71 UK centers. Randomized 1:1:1: conventional fractionation (74 Gy/37 fx) vs two hypofractionated schedules (60 Gy/20 fx or 57 Gy/19 fx), all with IMRT. Most patients received 3–6 months neoadjuvant/concurrent ADT. Primary question: are hypofractionated schedules non-inferior to conventional fractionation for efficacy and toxicity?
Interventions and follow up
Arm A: 74 Gy in 37 fractions (2 Gy/fx) IMRT over 7.4 week
Arm B: 60 Gy in 20 fractions (3 Gy/fx) IMRT over 4 week
Arm C: 57 Gy in 19 fractions (3 Gy/fx) IMRT over 3.8 week
Primary endpoint: Time to biochemical or clinical failure (non-inferiority)
mFollow up: Median 62.4 month
Arm B: 60 Gy in 20 fractions (3 Gy/fx) IMRT over 4 week
Arm C: 57 Gy in 19 fractions (3 Gy/fx) IMRT over 3.8 week
Primary endpoint: Time to biochemical or clinical failure (non-inferiority)
mFollow up: Median 62.4 month
Results
5-year biochemical/clinical failure-free survival: 74 Gy: 88.3%, 60 Gy: 90.6%, 57 Gy: 85.9%
Non-inferiority (60 Gy vs 74 Gy): HR 0.84 (90% CI 0.68–1.03), P(NI)=.0018 — non-inferior ✓
Non-inferiority (57 Gy vs 74 Gy): HR 1.20 (90% CI 0.99–1.46), P(NI)=.48 — non-inferiority NOT demonstrated
Side effects: No significant differences in grade ≥2 bowel or bladder AEs between arms at 5 years
Non-inferiority (60 Gy vs 74 Gy): HR 0.84 (90% CI 0.68–1.03), P(NI)=.0018 — non-inferior ✓
Non-inferiority (57 Gy vs 74 Gy): HR 1.20 (90% CI 0.99–1.46), P(NI)=.48 — non-inferiority NOT demonstrated
Side effects: No significant differences in grade ≥2 bowel or bladder AEs between arms at 5 years
Adverse events
Main adverse events: RTOG grade ≥2 bowel events at 5 years: 13.7% (74 Gy), 11.9% (60 Gy), 11.3% (57 Gy) — no significant differences. RTOG grade ≥2 bladder events: 9.1%, 11.7%, 6.6% — no significant differences. No treatment-related deaths.
Conclusions
Moderate hypofractionation (60 Gy/20 fx) is non-inferior to conventional fractionation (74 Gy/37 fx) for biochemical control with equivalent late toxicity. The 57 Gy/19 fx schedule failed non-inferiority and is not recommended. CHHiP established 60 Gy/20 fx as a new standard of care for localized prostate cancer IMRT in the UK and globally, offering a 4-week (vs 7.4-week) course with no loss of efficacy or increased toxicity.
Key Limitations
Key Limitations: Only 5-year follow-up reported here (median 62 months); longer-term data are important for slowly relapsing prostate cancer. Concurrent with CHHiP, RTOG 0415 and PROFIT trials also confirmed moderate hypofractionation. The 74 Gy arm is slightly lower than the 78 Gy optimal dose (per MDACC, MRC RT01); the 60 Gy/20 fx arm has a biologically equivalent dose of ~74 Gy (α/β=1.5), which may underestimate BED compared to 78 Gy conventional RT.
Clinical Context
CHHiP is the largest moderate hypofractionation trial for prostate cancer and, with PROFIT (Canada) and RTOG 0415 (US), established 60 Gy/20 fx as a standard fractionation schedule. Current international guidelines (NCCN, ESMO, EAU, AUA/ASTRO/ASTRO) endorse both conventional (78 Gy/39 fx) and moderate hypofractionation (60 Gy/20 fx or 70 Gy/28 fx) as standard options for localized prostate cancer. SBRT (5 fractions) has also been validated in PACE-B and HYPO-RT-PC for low/intermediate risk.
References