Higher-dose radiotherapy for high-risk prostate cancer paid off only at 10 years

Giving men with high-risk prostate cancer a higher radiotherapy dose on top of long-term hormone therapy improved how long they stayed free of disease progression — but the clearest evidence for that benefit showed up at ten years, not at the five-year mark the trial was actually built to test [s1]. The distinction matters, because the size of the advantage and its statistical footing look very different depending on when you measure.

Radiotherapy combined with long-term androgen deprivation therapy (ADT) is standard treatment for high-risk prostate cancer, but whether pushing the radiation dose higher adds anything has long been contested, with no prior demonstration of a benefit on cancer-specific or overall survival [s1]. GETUG AFU 18 set out to answer a narrower question: does raising the prostate dose by 10 Gy, from 70 Gy to 80 Gy, delay progression [s1]?

What the trial did

GETUG AFU 18 was a multicentre, open-label, randomised, phase 3 trial run at 25 centres in France [s1]. It enrolled patients with high-risk disease, defined as a prostate-specific antigen of 20 ng/mL or more, a Gleason score of at least 8, or clinical stage T3–T4 [s1]. Between April 6, 2009, and Jan 24, 2013, 505 patients were randomly assigned: 250 to dose-escalated radiotherapy delivered at 80 Gy in 2 Gy fractions over eight weeks, and 255 to standard-dose radiotherapy at 70 Gy in 2 Gy fractions over seven weeks, each alongside long-term ADT [s1]. Neither patients nor investigators were masked to the assigned dose [s1]. The prespecified primary endpoint was 5-year progression-free survival, requiring 197 events; because so few events had accrued by five years, the investigators additionally reported 10-year progression-free survival as a post-hoc analysis [s1]. The trial was registered before recruitment began [s2].

What it found

At a median follow-up of 9.5 years (IQR 8.5–10.3), 5-year progression-free survival was 91.4% (95% CI 87.0–94.4) with dose escalation versus 88.1% (83.2–91.6) with the standard dose — a modest gap [s1]. By ten years the difference had widened considerably: 83.6% (77.8–88.0) versus 72.2% (65.3–78.0), a stratified hazard ratio of 0.56 (95% CI 0.40–0.78, p<0.0001) [s1].

Toxicity was broadly similar between the arms. Grade 3 or worse acute adverse events at six months occurred in 60 (24%) of the dose-escalation group and 62 (25%) of the control group [s1]. The most frequent were sexual disorders (28 [11%] vs 20 [8%]) and bladder or urethra disorders (12 [5%] vs 19 [8%]) [s1]. Late toxicity assessed at five years occurred in 118 (70%) of 168 in the higher-dose group and 122 (73%) of 168 in the control group, with grade 3 or worse late events in 19 (8%) versus 17 (7%) [s1]. Serious adverse events occurred in nine (4%) patients in each group, none considered treatment related, and there were no treatment-related deaths [s1].

How to read it

The honest summary is that the trial's own prespecified comparison — progression-free survival at five years — showed only a small difference, and the more striking 10-year separation is a post-hoc result that the authors themselves flag as resting on a low number of events [s1]. That is a real caveat: a benefit that emerges most clearly outside the endpoint a trial was powered to detect deserves confirmation rather than celebration. The investigators are careful to say further research is needed to consolidate any effect on prostate cancer-specific or overall survival, neither of which this trial was designed or sized to establish [s1].

What GETUG AFU 18 does offer is reassurance on both counts a patient weighing dose escalation would care about: the higher dose did not come with meaningfully more serious toxicity over the follow-up reported, and long-term disease control was at least as good and probably better [s1]. The trial was funded by the French National Cancer Institute and by AstraZeneca, which markets prostate cancer drugs — worth noting even though the intervention here is radiation dose, not a product [s1].

Related coverage has examined when active surveillance is a reasonable alternative to immediate treatment, what the prostate-screening trials actually show, and adding a radioligand to hormone therapy in hormone-sensitive disease.

What to watch

The open question is whether the 10-year signal translates into a difference in the outcomes that matter most — metastasis-free, cancer-specific, and overall survival — and whether it holds in the era of image-guided and hypofractionated radiotherapy that has moved on from the technique tested here [s1]. Until then, GETUG AFU 18 is best read as supportive but not definitive evidence for pushing the dose.

This article describes trial results and is not medical advice. Radiotherapy dose and treatment choices in prostate cancer are decisions for treating clinicians.

Sources

• High-dose radiotherapy in high-risk prostate cancer (GETUG AFU 18) — The Lancet Oncology, 24 August 2026
• GETUG-AFU 18 trial registration (NCT00967863) — ClinicalTrials.gov, first posted 28 August 2009