CHHiP Trial and Prostate Cancer Treatment
Based on the landmark CHHiP trial, hypofractionated radiotherapy delivering 60 Gy in 20 fractions over 4 weeks is non-inferior to conventional 74 Gy in 37 fractions and should be adopted as the new standard of care for external beam radiotherapy in localized prostate cancer. 1
Key Findings from the CHHiP Trial
The CHHiP trial enrolled 3,216 men with localized prostate cancer (pT1b-T3aN0M0) between 2002-2011, with median follow-up of 62.4 months. 1
Efficacy Results
60 Gy in 20 fractions demonstrated non-inferiority to conventional 74 Gy in 37 fractions, with 5-year biochemical or clinical failure-free survival of 90.6% versus 88.3% (HR 0.84,90% CI 0.68-1.03, p=0.0018). 1
The 57 Gy in 19 fractions arm did NOT meet non-inferiority criteria (85.9% failure-free survival, HR 1.20, p=0.48), and therefore should not be used. 1
Most patients received 3-6 months of neoadjuvant and concurrent androgen suppression with radiotherapy. 1
Toxicity Profile
Long-term side effects were similar or potentially better with hypofractionation compared to conventional fractionation. 1
Bowel toxicity (RTOG grade ≥2): 11.9% at 60 Gy versus 13.7% at 74 Gy at 5 years 1
Bladder toxicity (RTOG grade ≥2): 11.7% at 60 Gy versus 9.1% at 74 Gy at 5 years 1
No treatment-related deaths occurred in any arm 1
Patient-reported outcomes showed no significant differences between arms 1
Supporting Evidence from Other Trials
A meta-analysis of randomized noninferiority trials (including CHHiP) demonstrated that hypofractionated RT improved disease-free survival compared to conventional fractionation (HR 0.869,95% CI 0.757-0.998, p=0.047) in men with intermediate-risk prostate cancer. 2
An independent randomized trial confirmed these findings, showing 85% 5-year biochemical-clinical failure-free survival in both hypofractionated (60 Gy in 20 fractions) and conventional (78 Gy in 39 fractions) arms, with no increase in grade ≥3 late toxicity. 3
Real-world data from 1,325 patients across 16 centers demonstrated excellent long-term outcomes with hypofractionation: 15-year biochemical relapse-free survival of 85.5% and cancer-specific survival of 98.5%, with very low rates of grade ≥3 late toxicity (1.6% GU, 0.9% GI). 4
Clinical Implementation Algorithm
Patient Selection
All patients with localized prostate cancer (T1b-T3aN0M0) requiring external beam radiotherapy are candidates for hypofractionated treatment. 1
Recommended Regimen
- Dose: 60 Gy in 20 fractions over 4 weeks 1
- Technique: Intensity-modulated radiotherapy (IMRT) with image-guided radiotherapy (IGRT) is mandatory 5, 1
- Androgen deprivation: Add 4-6 months for intermediate-risk disease; 2-3 years for high-risk disease 5
Risk-Stratified Approach
For intermediate-risk disease (Gleason 7, PSA 10-20, or T2b-c):
- 60 Gy in 20 fractions with IMRT/IGRT 1
- Consider 4-6 months neoadjuvant/concurrent/adjuvant ADT 5
- Consider pelvic lymph node irradiation 5
For high-risk disease (T3a, Gleason 8-10, or PSA >20):
- 60 Gy in 20 fractions with IMRT/IGRT 1
- Add 2-3 years of ADT (Category 1 recommendation) 5
- Include pelvic lymph node irradiation 5
For low-risk disease (T1-2a, Gleason ≤6, PSA <10):
- Consider active surveillance first 5, 6
- If radiotherapy chosen: 60 Gy in 20 fractions without ADT or pelvic nodal irradiation 5
Critical Technical Requirements
Image-guided radiotherapy (IGRT) is essential when delivering these doses, using CT, ultrasound with implanted fiducials, electromagnetic targeting/tracking, or endorectal balloon for daily prostate localization. 5
3D conformal or IMRT techniques must be used to minimize toxicity while maintaining tumor control. 5, 1
Common Pitfalls to Avoid
Do not use the 57 Gy in 19 fractions schedule from CHHiP, as it failed to demonstrate non-inferiority 1
Do not omit IGRT when using hypofractionation, as precise daily localization is critical for safety 5
Do not use neoadjuvant ADT before radical prostatectomy (strongly discouraged), but it is appropriate before/during radiotherapy for intermediate and high-risk disease 5
Patients with very large prostates, high bladder outlet obstruction symptoms, or previous TURP may require neoadjuvant ADT to shrink the prostate before brachytherapy, but this does not apply to external beam hypofractionation 5
Advantages Over Conventional Fractionation
Hypofractionation offers significant practical benefits: