Multicenter phase 3 trial of high-dose radiotherapy in patients with high-risk prostate cancer treated with long-term androgen deprivation therapy

Prof. Christophe Hennequin

For patients with high-risk prostate cancer, the role of dose-escalated radiotherapy in combination with long-term androgen deprivation therapy (ADT) is controversial. The multicenter phase 3 GETUG AFU 18 trial, at 25 centers in France, evaluated the effect of a 10 Gy dose increase, from 70 Gy to 80 Gy, on progression-free survival in men with high-risk prostate cancer (PSA 20 ng/mL or more, Gleason score at least 8, or clinical state T3-T4). Patients were randomized 1:1 to receive prostate-targeted dose-escalated EBRT (80 Gy, 2 Gy per fraction for 8 weeks; n=250) or standard-dose EBRT (70 Gy; 2 Gy per fraction for 7 weeks; n=255), combined with long-term ADT. The primary endpoint was 5-year progression-free survival (PFS) defined as the time from randomization to first biochemical or clinical disease progression. At a median follow-up of 9.5 years (IQR 8.5-10.3), 5-year PFS rate was 91.4% in the dose-escalation group versus 88.1% in the control group, and the 10-year PFS rate was 83.6% versus 72.2% (sHR 0.56; p<0.0001). Grade 3 or worse adverse events assessed at 6 months (acute toxicity) were observed in 24% versus 25%. Adverse events assessed at 5 years (late toxicity) occurred in 70% versus 73%; grade 3 or worse late toxicities occurred in 8% versus 7%. There were no treatment-related deaths. The authors conclude that for patients with high-risk prostate cancer, radiotherapy at a total dose of 80 Gy, in combination with long-term ADT, improved PFS and could be a potential option in this situation. However, given the low number of events, further research is needed to consolidate and confirm the benefit in dose-escalation in prostate cancer-specific survival and overall survival.