Background
Phase III RCT (PACE-B — Prostate Advances in Comparative Evidence B). 874 men with low-to-intermediate-risk prostate cancer (PSA ≤20 ng/mL, Gleason ≤7 [3+4], clinical stage T1–T2, excluding Gleason 4+3) enrolled 2012–2018 at 37 centers (UK, Ireland, Canada). Randomized 1:1: standard-of-care radiotherapy (conventionally fractionated 78 Gy/39 fx or moderately hypofractionated 62 Gy/20 fx) vs stereotactic body radiotherapy (SBRT: 36.25 Gy/5 fx over 1–2 weeks). Androgen deprivation was not permitted. The Brand Lancet Oncol 2019 paper reports the acute toxicity analysis (coprimary endpoint); longer-term efficacy data from PACE-B await maturity.
Interventions and follow up
Arm A: Standard-of-care RT: 78 Gy/39 fx OR 62 Gy/20 fx (investigator's choice), IMRT/VMAT
Arm B: SBRT: 36.25 Gy in 5 fractions (7.25 Gy/fx) over 1–2 weeks, SABR technique
Primary endpoint: Coprimary: (1) freedom from biochemical/clinical failure (oncologic; not yet reported); (2) worst acute RTOG GI or GU toxicity score ≥grade 2 at 12 weeks (acute toxicity; reported in Brand 2019)
mFollow up: 12 weeks for acute toxicity; oncologic follow-up ongoing
Arm B: SBRT: 36.25 Gy in 5 fractions (7.25 Gy/fx) over 1–2 weeks, SABR technique
Primary endpoint: Coprimary: (1) freedom from biochemical/clinical failure (oncologic; not yet reported); (2) worst acute RTOG GI or GU toxicity score ≥grade 2 at 12 weeks (acute toxicity; reported in Brand 2019)
mFollow up: 12 weeks for acute toxicity; oncologic follow-up ongoing
Results
Acute grade ≥2 GI toxicity (12 weeks): 12% standard RT vs 10% SBRT (difference −1.9 pp, 95% CI −6.2 to 2.4; P=.38) — not significantly different
Acute grade ≥2 GU toxicity (12 weeks): 27% standard RT vs 23% SBRT (difference −4.2 pp, P=.16) — not significantly different
No treatment-related deaths:
Acute grade ≥2 GU toxicity (12 weeks): 27% standard RT vs 23% SBRT (difference −4.2 pp, P=.16) — not significantly different
No treatment-related deaths:
Adverse events
Main adverse events: Acute RTOG grade ≥2 GI: 10–12% both arms. Acute grade ≥2 GU: 23–27% both arms. SBRT did not significantly increase either acute GI or acute GU toxicity, in contrast to the HYPO-RT-PC experience (which showed higher acute GU toxicity with SBRT). No grade 4–5 treatment-related acute events.
Conclusions
SBRT (36.25 Gy/5 fx) did not increase acute GI or GU toxicity compared with standard-of-care radiotherapy for low-to-intermediate-risk prostate cancer. This contrasts with HYPO-RT-PC data showing higher acute toxicity with SBRT, possibly reflecting differences in SBRT technique (5 fx vs 7 fx, CyberKnife vs linac). Long-term oncologic efficacy data are pending.
Key Limitations
Key Limitations: Acute toxicity analysis only — oncologic primary endpoint not yet reported. Investigator choice of standard arm (conventional vs moderate hypofractionation) introduced heterogeneity. Excludes high-risk patients and Gleason 4+3. ADT not permitted — does not address SBRT for higher-risk patients typically receiving ADT. Direct comparison with HYPO-RT-PC (different schedule) is difficult due to patient selection and technique differences.
Clinical Context
PACE-B is the key RCT establishing acute safety of prostate SBRT vs standard radiotherapy in low/intermediate-risk disease. Combined with HYPO-RT-PC (which showed non-inferiority for efficacy), PACE-B provides important reassurance about the acute safety profile of 5-fraction SBRT. The 5-fraction (36.25 Gy) schedule is used at most US/UK SBRT centers and is endorsed by AUA/ASTRO/ASTRO and NCCN for experienced centers. Longer-term PACE-B efficacy data (first published in 2024, showing non-inferiority at 5 years) have further established SBRT as a standard option for low-intermediate risk prostate cancer.
References