Dose-escalated 80 Gy radiotherapy with long-term ADT improved 10-year progression-free survival

Design

Phase 3, open-label, randomised, 25 French centres

Population

505 men with high-risk prostate cancer on long-term ADT

Primary outcome

5-year progression-free survival (10-year reported post hoc)

Effect

10-year PFS 83.6% vs 72.2%, HR 0.56 (0.40-0.78); 5-year 91.4% vs 88.1%

GETUG AFU 18 was an open-label phase 3 trial at 25 French centres. 505 men with high-risk prostate cancer (PSA 20 ng/mL or more, Gleason 8 or more, or T3-T4) receiving long-term androgen deprivation were randomised to 80 Gy or 70 Gy in 2 Gy fractions.

At a median 9.5 years, 5-year progression-free survival was 91.4% vs 88.1%. At 10 years it was 83.6% vs 72.2% (HR 0.56, 95% CI 0.40-0.78). Severe acute toxicity was similar (24% vs 25%), as was severe late toxicity (8% vs 7%); late grade 3 bladder or urethral events were 4% vs 2%. There were no treatment-related deaths.

Whether dose escalation adds anything once long-term ADT is given has been disputed, because earlier trials were run largely without hormones. This trial shows a clinically meaningful and durable reduction in progression with little extra harm.

Most modern regimens already deliver escalated biologically effective doses through hypofractionation. For centres still using 70 Gy conventional schedules with ADT for high-risk disease, this is a reason to change.

• Deliver dose-escalated radiotherapy (80 Gy equivalent) with long-term ADT for high-risk prostate cancer.
• Audit whether any local high-risk pathways still use 70 Gy.
• Counsel about a small increase in late bladder or urethral toxicity.
• Discuss that survival benefit has not yet been shown.

Why it matters

It settles whether radiotherapy dose still matters when long-term hormones are given: it does, for progression at least.

Don't overread it

The 10-year analysis was post hoc because 5-year events were few, and no benefit in cancer-specific or overall survival has been shown.

The statistics, in plain English

The prespecified 5-year result was not clearly different, which is why the 10-year analysis, added afterwards, carries less weight than a primary endpoint. A hazard ratio of 0.56 means the progression rate was about 44% lower with 80 Gy over follow-up.

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