Background
Multicentre, open-label, randomised phase 3 (25 French centres). N=505. High-risk localised prostate cancer (PSA ≥20 ng/mL, Gleason ≥8, or cT3–T4). Tests whether 10 Gy dose escalation (80 vs 70 Gy) improves PFS when combined with long-term ADT. Minimisation stratified by centre and prior pelvic lymph node dissection.
Results
Interventions and follow up: Arm A: Dose-escalated EBRT 80 Gy (2 Gy/fx, 8 weeks) + long-term ADT
Arm B: Standard EBRT 70 Gy (2 Gy/fx, 7 weeks) + long-term ADT
Primary endpoint: 5-year PFS (biochemical [PSA nadir + 2] or clinical progression); 10-yr PFS reported post hoc
mFollow up: 9.5 years
Results: 5-yr PFS: 91.4% vs 88.1%
10-yr PFS (post hoc): 83.6% vs 72.2%; stratified HR 0.56 (95% CI 0.40–0.78); P<.0001
Prostate cancer-specific survival: NR in abstract
OS: NR in abstract
Arm B: Standard EBRT 70 Gy (2 Gy/fx, 7 weeks) + long-term ADT
Primary endpoint: 5-year PFS (biochemical [PSA nadir + 2] or clinical progression); 10-yr PFS reported post hoc
mFollow up: 9.5 years
Results: 5-yr PFS: 91.4% vs 88.1%
10-yr PFS (post hoc): 83.6% vs 72.2%; stratified HR 0.56 (95% CI 0.40–0.78); P<.0001
Prostate cancer-specific survival: NR in abstract
OS: NR in abstract
Adverse events
Acute grade ≥3 (6 mo): 24% vs 25%
Acute grade ≥3 by type: sexual disorders 11% vs 8%; bladder/urethra 5% vs 8%
Late any-grade (5 yr): 70% vs 73%
Late grade ≥3 (5 yr): 8% vs 7% (bladder/urethra 4% vs 2%)
Serious AEs: 4% vs 4%; no treatment-related deaths
Acute grade ≥3 by type: sexual disorders 11% vs 8%; bladder/urethra 5% vs 8%
Late any-grade (5 yr): 70% vs 73%
Late grade ≥3 (5 yr): 8% vs 7% (bladder/urethra 4% vs 2%)
Serious AEs: 4% vs 4%; no treatment-related deaths
Conclusions
In high-risk prostate cancer treated with long-term ADT, escalating EBRT from 70 to 80 Gy improved long-term PFS (10-yr 83.6% vs 72.2%, HR 0.56) without added grade ≥3 toxicity. Supports dose escalation as a standard component of definitive RT + ADT for high-risk disease.
Key Limitations
Open-label. Prespecified 5-year PFS analysis was underpowered (few events) so the headline result rests on a post hoc 10-year endpoint. PFS driven largely by biochemical progression; survival endpoints not in abstract and need confirmation. Enrolled 2009–2013 with conventional fractionation and 3D/IMRT of that era; relevance to modern moderate hypofractionation, brachytherapy boost, and ARPI intensification (STAMPEDE abiraterone) is uncertain. Pelvic nodal RT not standardised.
Clinical Context
Prior dose-escalation trials (RTOG 0126, MRC RT01, GETUG 06) showed biochemical benefit but no survival gain, mostly without long-term ADT. GETUG AFU 18 (ASCO 2024 plenary) is the first phase 3 to show dose escalation improves outcomes on top of long-term ADT in high-risk disease. NCCN and ESMO already recommend high-dose RT (≥76–80 Gy or equivalent, or brachytherapy boost) with 18–36 months ADT for high-risk prostate cancer; this trial provides the randomised support.