Dose-escalated radiotherapy in high-risk prostate cancer has been contested for years, because the trials showing biochemical benefit were done before long-term androgen deprivation became standard, leaving open whether the extra dose adds anything once hormones are optimised. GETUG AFU 18 answered that directly. At 25 French centres, 505 men with high-risk disease — PSA 20 ng/mL or above, Gleason 8 or above, or clinical stage T3 to T4 — all receiving long-term androgen deprivation, were randomised to 80 Gy over 8 weeks or 70 Gy over 7 weeks.
At a median follow-up of 9.5 years, five-year progression-free survival was 91.4% against 88.1% — a modest gap, and the reason the trial reported ten-year data post hoc. At ten years the separation was clear: 83.6% (95% CI 77.8 to 88.0) against 72.2% (65.3 to 78.0), stratified hazard ratio 0.56 (95% CI 0.40 to 0.78, p<0.0001).
Toxicity is the part that makes this actionable. Grade 3 or worse acute adverse events at 6 months occurred in 24% of the 80 Gy arm and 25% of the 70 Gy arm. Late grade 3 or worse toxicity at 5 years was 8% against 7%. Bladder and urethral problems, the expected cost of dose escalation, were 4% against 2% for late grade 3 events. Serious adverse events were 4% in both arms and none were treatment-related. Ten extra grays bought an 11-percentage-point absolute gain at ten years for what is, on these numbers, a negligible toxicity price.
Two honest caveats. The benefit is in progression-free survival, driven substantially by biochemical progression, and the trial was not powered for cancer-specific or overall survival — the authors say so explicitly. And the ten-year analysis was post hoc, added because five-year events were too few, which weakens it relative to a prespecified endpoint even though the direction was consistent.
For Indian practice the constraint is machine time. Eight weeks of daily fractions against seven is a 14% increase in linac occupancy per patient, in a system where waiting lists are the binding limit on who gets treated at all. That is a real trade-off and worth naming, particularly as moderate hypofractionation offers another route to biologically equivalent dose escalation in fewer fractions.
- Offer 80 Gy rather than 70 Gy to men with high-risk prostate cancer receiving long-term androgen deprivation.
- Quote the ten-year figure: 83.6% against 72.2% progression-free, an 11-point absolute gain.
- Reassure on toxicity — acute and late grade 3 or worse rates were essentially identical between arms.
- Be clear that the endpoint is progression-free survival; cancer-specific and overall survival were not shown.
- Weigh the extra week of machine time against waiting-list pressure, and consider hypofractionated equivalents.
The statistics, in plain English
The gap between the five-year and ten-year results is instructive. At five years only a few events had occurred, so the curves had barely separated; the difference emerged with time, which is typical for a local treatment effect in a slow-growing cancer. But the ten-year analysis was post hoc — decided after the data were seen — and post hoc analyses carry less weight because the choice of when to look can itself be influenced by the result. The hazard ratio of 0.56 with an interval of 0.40 to 0.78 is a strong signal, and its consistency with the five-year direction supports it. What none of this establishes is that men live longer; biochemical progression is a marker that often precedes clinical events by many years, and sometimes by more years than the patient has.
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