HYPO-RT-PC
ForIntermediate/high-risk N0M0 prostate, PSA ≤20, no ADT, age ≤75
5yr FFS 84% vs 84%
adjusted HR 1.002 (95% CI 0.758-1.325), non-inferior vs HR limit 1.338
TL;DR5yr FFS 84% vs 84%, adjusted HR 1.002 (95% CI 0.758-1.325): 42.7 Gy/7 fx non-inferior to 78 Gy/39 fx in intermediate-to-high-risk prostate, no ADT.
The schedule tested is 42.7 Gy/7 fx every other weekday to a prostate-only CTV (no seminal vesicles) with a 7 mm fiducial margin, 80% 3DCRT, no ADT. That supports UHF for prostate-only volumes without ADT, not SV-inclusive or ADT-paired high-risk plans. Counsel on the 1yr G2+ GU bump (6% vs 2%).
In a man up to 75 with intermediate-risk, N0M0 prostate cancer, PSA ≤20 and no ADT planned, this supports 7-fraction UHF as disease-control equivalent to 39 fractions; it does not extend to pts needing ADT, PSA >20, or seminal vesicle coverage.
The schedule tested is 42.7 Gy/7 fx every other weekday to a prostate-only CTV (no seminal vesicles) with a 7 mm fiducial margin, 80% 3DCRT, no ADT. That supports UHF for prostate-only volumes without ADT, not SV-inclusive or ADT-paired high-risk plans. Counsel on the 1yr G2+ GU bump (6% vs 2%).
10 details 5 trials watching
Open-label randomised phase 3 non-inferiority trial, 1:1, 12 centres in Sweden and Denmark, N=1200 randomised 2005-2015. Median follow-up 5.0 yr (IQR 3.1-7.0).
Men up to 75 with intermediate-to-high-risk, T1c-T3a N0M0 prostate cancer, PSA ≤20, WHO PS 0-2. No ADT allowed. 89% intermediate risk, 11% high risk.
42.7 Gy/7 fx (3 d/wk, 2.5 wk) vs 78.0 Gy/39 fx (5 d/wk, 8 wk), prescribed as mean PTV dose and designed equi-effective for late effects at α/β = 3 Gy. CTV prostate only, no seminal vesicles; 7 mm isotropic margin with fiducials; 80% 3DCRT.
Primary: failure-free survival (Phoenix nadir+2 biochemical or clinical failure), per-protocol, NI margin 4% at 5yr (critical HR 1.338). Secondary: OS, PCSS, RTOG toxicity, erectile function.
Efficacy and toxicity by arm are tabulated above; the primary met NI with a point estimate of essentially no difference.
| Endpoint | UHF 42.7 Gy/7 fx | CF 78.0 Gy/39 fx | Comparison |
|---|---|---|---|
| 5yr FFS | 84% (80-87) | 84% (80-87) | adj HR 1.002 (0.758-1.325) |
| 5yr OS | 94% (92-96) | 96% (95-98) | HR 1.11 (0.73-1.69) |
| Acute G2+ GU, end RT | 28% (158/569) | 23% (132/578) | p=0.057 |
| G2+ GU at 1yr | 6% (32/528) | 2% (13/529) | p=0.0037 |
| G2+ GU at 5yr | 5% (11/243) | 5% (12/249) | p=1.00 |
| G2+ bowel at 5yr | 1% (3/244) | 4% (9/249) | p=0.14 |
| Endpoint | UHF | CF | Log-rank p |
|---|---|---|---|
| GU at 2yr | 13% (11-16) | 9% (7-12) | 0.63 |
| GU at 5yr | 18% (15-22) | 17% (14-20) | 0.63 |
| Bowel at 2yr | 6% (5-9) | 5% (4-8) | 1.00 |
| Bowel at 5yr | 10% (7-13) | 10% (7-13) | 1.00 |
UHF carries a higher acute and 1yr GU burden (G2+ at 1yr 6% vs 2%, p=0.0037) that converges by 5yr (5% vs 5%). Late bowel toxicity no different; patient-reported acute urinary and bowel symptoms higher with UHF.
CHHiP, RTOG 0415, PROFIT and HYPRO established moderate hypofractionation against conventional fractionation. HYPO-RT-PC is the first randomised test of ultra-hypofractionation, the evidence the 2018 ASTRO/ASCO/AUA guideline said it was waiting for.
The upper CI bound (1.325) clears the 1.338 limit narrowly. 80% 3DCRT and a 7 mm margin predate modern SBRT delivery, and 7 fx every other weekday is not the 5 fx schedule most programs use. Five-year median follow-up is short for late intermediate-risk failures.
The trial settles disease-control equivalence of UHF for prostate-only, ADT-free treatment. It leaves open UHF with ADT, with SV or nodal coverage, and against moderate hypofractionation.
CONSORT flow
Randomised phase 3, NI primary met at 5yr median f/u; open-label, per-protocol primary, redesigned from superiority mid-trial. Backs guideline-conditional UHF rather than redefining SOC alone.
- UHF with concurrent ADT or seminal vesicle coverage in high-risk disease n=120 · primary completion 2027-12 · randomized SBRT vs 76 Gy/38 fx IMRT, high-risk N0n=700 · primary completion 2033-10 · phase 3 2x2: SBRT dose escalation ± darolutamide, high-risk
- UHF versus moderate hypofractionation head-to-head active Radiation Hypofractionation Via Extended Versus Accelerated Therapy (HEAT) For Prostate Cancer Phase NAn=161 · primary completion 2027-02 · 36.25 Gy/5 fx vs 70.2 Gy/26 fx, 4-yr BF non-inferiorityn=503 · primary completion 2028-08 · moderate hypo vs SBRT vs EBRT+SBRT boost; BF, toxicityactive Standard Moderately Hypofractionated RT vs. Ultra-hypofractionated Focal Lesion Ablative Microboost in Prostate Cancer Phase NAn=484 · primary completion 2032-01 · UHF focal microboost vs 20-fx moderate hypo, int/high risk
- Late biochemical failure beyond 5-year median follow-up
📚 Sources · 📄 1 paper
The longer read
The question HYPO-RT-PC answers is narrower than its headline. Moderate hypofractionation was already established by CHHiP, RTOG 0415, PROFIT and HYPRO, and the 2018 ASTRO/ASCO/AUA guideline still graded ultra-hypofractionation as conditional because no randomised data existed. This trial supplies that randomised comparison, but against dose-escalated conventional fractionation (78 Gy in 39 fractions), not against the moderate schedules most centres had already moved to. A reader choosing between a moderate schedule and an ultra-hypofractionated one gets indirect support here, not a head-to-head answer.
The efficacy result is as clean as non-inferiority results get on the point estimate: identical 5-year failure-free survival of 84% and an adjusted HR of 1.002. The confidence interval tells a more careful story. Its upper bound of 1.325 sits just below the prespecified limit of 1.338, so the data rule out a meaningful disadvantage only by a small cushion. The margin itself was set after the trial was converted from a superiority design, prompted by a blinded interim that estimated 87% failure-free survival overall. Because that interim was blinded to arm, the redesign does not look like outcome-driven goalpost moving, but the reader should know the 4% margin was chosen mid-course. The per-protocol primary is a common worry in non-inferiority trials, since it can flatter equivalence; here the per-protocol and ITT populations differ by 10 pts, so that concern is close to moot.
Transferability is where the RT details matter most. The schedule was 42.7 Gy in 7 fractions given three days a week, prescribed to the mean PTV dose, to a prostate-only CTV that excluded the seminal vesicles, with a 7 mm isotropic margin and 3DCRT in 80% of pts. That is not the five-fraction SBRT most programs deliver today, and the direction of the difference cuts both ways: tighter modern margins and IMRT should reduce toxicity, while a higher dose per fraction and a shorter course could raise it. The absence of ADT and the small high-risk fraction (11%) mean the result says little about unfavourable disease where ADT or seminal vesicle coverage is standard.
The toxicity pattern deserves a specific counselling conversation rather than a summary of equivalence. UHF produced more acute urinary morbidity and a real bump in grade 2 or worse urinary toxicity at one year (6% vs 2%), and cumulative late urinary toxicity at two years ran 13% vs 9% before converging to 18% vs 17% at five years. Toxicity grading was unblinded, though patient-reported outcomes moved in the same direction, which makes the signal more believable rather than less.
What would make the conclusion wrong is late biochemical failure. Median follow-up of five years is short for an intermediate-risk population, and prostate cancer deaths (11 vs 8) are too few to read. The decision this moves is fraction number for prostate-only, ADT-free treatment; it does not settle ultra-hypofractionation with ADT, with elective volumes, or against moderate hypofractionation.