Background
Phase III RCT (HYPO-RT-PC). 1,200 patients with intermediate-to-high-risk localized prostate cancer (T1c–T3a, Gleason ≤7 [3+4], PSA ≤20 ng/mL) from 12 Swedish and 1 Norwegian centers, enrolled 2005–2015. Randomized 1:1: ultra-hypofractionated SBRT (42.7 Gy/7 fx, 3 times/week) vs conventional fractionation (78 Gy/39 fx). Conducted without ADT in both arms. This is the largest RCT of SBRT for prostate cancer vs conventional RT, demonstrating non-inferiority.
Interventions and follow up
Arm A: Ultra-hypofractionated SBRT: 42.7 Gy in 7 fractions (6.1 Gy/fx), 3 fractions/week, without ADT
Arm B: Conventional RT: 78 Gy in 39 fractions (2 Gy/fx), without ADT
Primary endpoint: Failure-free survival (non-inferiority; Δ failure-free survival non-inferiority margin: 4%)
mFollow up: Median 5 year
Arm B: Conventional RT: 78 Gy in 39 fractions (2 Gy/fx), without ADT
Primary endpoint: Failure-free survival (non-inferiority; Δ failure-free survival non-inferiority margin: 4%)
mFollow up: Median 5 year
Results
5-year failure-free survival: 84% SBRT vs 84% conventional — non-inferior (HR 1.002, 90% CI 0.758–1.325)
OS: No significant difference at 5 years
PSA nadir: Lower with SBRT than conventional RT (better long-term PSA control trend)
OS: No significant difference at 5 years
PSA nadir: Lower with SBRT than conventional RT (better long-term PSA control trend)
Adverse events
Main adverse events: Acute grade ≥2 GU toxicity: 28% SBRT vs 5% conventional (P<.001). Late grade ≥2 GU toxicity at 2 years: 5% SBRT vs 2% conventional (P=.057). Late grade ≥2 GI toxicity at 2 years: 9% SBRT vs 5% conventional (P=.11). Higher patient-reported urinary and bowel symptoms with SBRT in short term, but converging at 2–5 years. No treatment-related deaths.
Conclusions
Ultra-hypofractionated SBRT (42.7 Gy/7 fx) is non-inferior to conventional fractionation (78 Gy/39 fx) for failure-free survival in intermediate-to-high-risk prostate cancer. SBRT significantly increased acute GU toxicity and trended toward higher late GU/GI toxicity, but with convergence at 5 years. SBRT treatment course is substantially shorter (2.5 weeks vs 8 weeks) with equivalent oncologic outcomes.
Key Limitations
Key Limitations: Higher acute toxicity with SBRT is clinically significant — patients experienced substantially more urinary symptoms during and immediately after SBRT. The non-inferior efficacy at 5 years may not capture late relapses in prostate cancer. No ADT in either arm — does not address the question in high-risk patients routinely receiving long-term ADT. The 42.7 Gy/7 fx schedule (3 fx/week) is different from the US standard (36.25 Gy/5 fx) used in PACE-B.
Clinical Context
HYPO-RT-PC, together with PACE-B, establishes ultra-hypofractionated SBRT as a non-inferior option to conventional fractionation for localized prostate cancer. HYPO-RT-PC uses 42.7 Gy/7 fx (7-fraction schedule from Sweden), while PACE-B uses 36.25 Gy/5 fx (5-fraction US/UK schedule). Both demonstrate non-inferiority for oncologic outcomes with shorter treatment courses. NCCN, EAU, and AUA/ASTRO/ASTRO/ASTRO guidelines now endorse SBRT as a standard treatment option for low- and intermediate-risk prostate cancer at experienced centers.
References
References: Widmark A et al, Lancet 2019 (HYPO-RT-PC trial)