HYPO-RT-PC
Ultra-hypofractionated versus conventionally fractionated radiotherapy for prostate cancer: the HYPO-RT-PC randomised, non-inferiority, phase 3 trial
Phase 3N = 1,200
- Population
- Men up to 75 years of age with intermediate-to-high-risk prostate cancer (89% intermediate risk, 11% high risk) and WHO performance status 0 to 2
- Design
- Open-label randomised non-inferiority phase 3 trial in 12 centres in Sweden and Denmark, July 2005 to November 2015: 1200 men up to 75 years of age with intermediate-to-high-risk prostate cancer were assigned to ultra-hypofractionation (42.7 Gy in seven fractions, 3 days per week for 2.5 weeks; 598) or conventional fractionation (78.0 Gy in 39 fractions, 5 days per week for 8 weeks; 602). No androgen deprivation therapy was allowed. Primary endpoint: time to biochemical or clinical failure, analysed in the per-protocol population (1180 patients); prespecified non-inferiority margin 4% at 5 years (critical hazard ratio 1.338). Registered as ISRCTN45905321.
- Primary endpoint
- BCF-free survival
- Arms
- 78 Gy in 39 fractions (control, n = 602): 78.0 Gy in 39 fractions, 5 days per week for 8 weeks
- 42.7 Gy in 7 fractions (experimental, n = 598): 42.7 Gy in seven fractions, 3 days per week for 2.5 weeks
- People
- Widmark A, senior author Nilsson P
BCF-free survivalHR 1.002 (95% CI 0.758–1.325)Δ 60-month BCF-free survival0 pointsΔ RTOG grade 2 or worse genitourinary toxicity+5 pointsΔ 12-month RTOG grade 2 or worse genitourinary toxicity+4 pointsΔ 60-month RTOG grade 2 or worse genitourinary toxicity0 pointsΔ 60-month RTOG grade 2 or worse gastrointestinal toxicity−3 points
Show the numbers
| Endpoint | Analysis | 42.7 Gy in 7 fractions | 78 Gy in 39 fractions | Effect |
|---|---|---|---|---|
| BCF-free survivalPer-protocol population (1180 of 1200 patients)Estimated failure-free survival at 5 years (primary endpoint: time to biochemical or clinical failure) | primarymedian follow-up 5 yearsWidmark 2019 | 84% at 5 y (80–87%) | 84% at 5 y (80–87%) | HR 1.002 (95% CI 0.758–1.325)P=0.99Adjusted hazard ratio; log-rank P value. |
| RTOG grade 2 or worse genitourinary toxicityPatients assessed at end of radiotherapy (569 and 578)Acute physician-reported RTOG grade 2 or worse urinary toxicity at end of radiotherapy | primaryWidmark 2019 | 28% | 23% | P=0.057158 of 569 vs 132 of 578; the abstract calls this weak evidence of an increase with ultra-hypofractionation. Patient-reported acute urinary and bowel symptoms were significantly higher with ultra-hypofractionation. |
| RTOG grade 2 or worse genitourinary toxicityPatients assessed at 1 year (528 and 529)Physician-reported RTOG grade 2 or worse urinary toxicity at 1-year follow-up | primaryWidmark 2019 | 6% at 12 mo | 2% at 12 mo | P=0.003732 of 528 vs 13 of 529. |
| RTOG grade 2 or worse genitourinary toxicityPatients assessed at 5 years (243 and 249)Physician-reported RTOG grade 2 or worse urinary toxicity at 5 years | primaryWidmark 2019 | 5% at 5 y | 5% at 5 y | P=1.0011 of 243 vs 12 of 249. |
| RTOG grade 2 or worse gastrointestinal toxicityPatients assessed at 5 years (244 and 249)Physician-reported RTOG grade 2 or worse bowel toxicity at 5 years | primaryWidmark 2019 | 1% at 5 y | 4% at 5 y | P=0.143 of 244 vs 9 of 249. |
| Endpoint | Analysis | 42.7 Gy in 7 fractions | 78 Gy in 39 fractions | Effect |
|---|---|---|---|---|
| BCF-free survivalPer-protocol population (1180 of 1200 patients)Estimated failure-free survival at 5 years (primary endpoint: time to biochemical or clinical failure) | primarymedian follow-up 5 yearsWidmark 2019 | 84% at 5 y (80–87%) | 84% at 5 y (80–87%) | HR 1.002 (95% CI 0.758–1.325)P=0.99Adjusted hazard ratio; log-rank P value. |
| RTOG grade 2 or worse genitourinary toxicityPatients assessed at end of radiotherapy (569 and 578)Acute physician-reported RTOG grade 2 or worse urinary toxicity at end of radiotherapy | primaryWidmark 2019 | 28% | 23% | P=0.057158 of 569 vs 132 of 578; the abstract calls this weak evidence of an increase with ultra-hypofractionation. Patient-reported acute urinary and bowel symptoms were significantly higher with ultra-hypofractionation. |
| RTOG grade 2 or worse genitourinary toxicityPatients assessed at 1 year (528 and 529)Physician-reported RTOG grade 2 or worse urinary toxicity at 1-year follow-up | primaryWidmark 2019 | 6% at 12 mo | 2% at 12 mo | P=0.003732 of 528 vs 13 of 529. |
| RTOG grade 2 or worse genitourinary toxicityPatients assessed at 5 years (243 and 249)Physician-reported RTOG grade 2 or worse urinary toxicity at 5 years | primaryWidmark 2019 | 5% at 5 y | 5% at 5 y | P=1.0011 of 243 vs 12 of 249. |
| RTOG grade 2 or worse gastrointestinal toxicityPatients assessed at 5 years (244 and 249)Physician-reported RTOG grade 2 or worse bowel toxicity at 5 years | primaryWidmark 2019 | 1% at 5 y | 4% at 5 y | P=0.143 of 244 vs 9 of 249. |
Data table
| Endpoint | HR | 95% CI |
|---|---|---|
| BCF-free survival | 1.002 | 0.758–1.325 |
Appears in
Sources
Widmark A, Gunnlaugsson A, Beckman L, Thellenberg-Karlsson C, Hoyer M, Lagerlund M, et al. Ultra-hypofractionated versus conventionally fractionated radiotherapy for prostate cancer: 5-year outcomes of the HYPO-RT-PC randomised, non-inferiority, phase 3 trial. Lancet. 2019;394(10196):385-395.