ESTRO 2025 congress report | Clinical track
Late-Breaking Papers Session, Saturday 3 May 2025

Report by the ESTRO urology focus group

The landmark trial of the use of hypofractionated radiotherapy for prostate cancer (HYPO-RT-PC) provides level 1 evidence in support of the application of ultra-hypofractionated (UHF) radiotherapy in the treatment of intermediate-to-high-risk localised prostate cancer. The Scandinavian phase 3 non-inferiority trial, which was presented at ESTRO 2025 by Dr Thellenberg Karlsson, randomised 1,180 patients to receive either UHF (42.7Gy in seven fractions over 2.5 weeks) or conventionally fractionated (CF) radiotherapy (78.0Gy in 39 fractions over eight weeks), with androgen deprivation therapy (ADT) excluded in both treatment arms.

The study cohort predominantly involved patients with intermediate-risk disease (89%), with a minority (11%) classified as high risk. Treatment was focused on the prostate using a 7mm planning target volume margin, delivered via 3D-conformal radiotherapy (3D-CRT) guided by fiducial markers.

After a median follow-up duration of 10.6 years, UHF was shown to be non-inferior to CF in terms of failure-free survival (FFS), with 10-year FFS rates of 72% for UHF compared with 65% for CF (adjusted hazard ratio = 0.84, 95% confidence interval: 0.69-1.03). Kaplan-Meier curves were comparable for approximately six years after treatment before diverging in favour of UHF, with the difference reaching statistical significance at the 10-year mark (p = 0.025). These findings generated the hypothesis that the shorter course might actually be superior in the long run.

Ten-year overall survival rates were similar between arms (81% for UHF vs. 79% for CF, p = 0.34), as was the proportion of patients remaining free from ADT (77% vs. 75%, p = 0.36). The cumulative incidence of prostate-cancer-specific mortality was identical at 4% in both groups.

Rates of late grade ≥2 genitourinary (GU) toxicity were equivalent (27% for UHF vs. 28% for CF, p = 0.78), as were rates of late grade ≥2 gastrointestinal toxicity (14% vs. 15%, p = 0.49). A transient increase in GU toxicity was observed in the UHF cohort at 12 months, but it resolved with extended follow-up.

These outcomes confirm and extend the five-year results previously published in The Lancet (2019). They offer robust, long-term support for UHF as a safe and effective treatment modality for intermediate-risk prostate cancer. Despite advancements in clinical practice since the trial’s initiation, the findings remain pertinent to contemporary treatment paradigms. Indeed, the wide use of 3D-CRT to deliver extremely hypofractionated radiotherapy emphasises the radiobiological rationale behind the use of UHF, rather than a direct assessment of modern and more precise stereotactic body radiotherapy (SBRT). Notably, the demonstration of efficacy in the absence of ADT is particularly advantageous for patients who wish to avoid hormonal therapy.

Overall, these results lend indirect support to emerging evidence in favour of five-fraction SBRT, such as that from the PACE-B trial. Taken together, these observations clearly support the use of shortened radiation schedules in the treatment of prostate cancer, as they result in a significant quality-of-life advantage and potentially lower healthcare costs.

Prof Stefano Arcangeli
Radiotherapy unit director
San Gerardo dei Tintori IRCCS Foundation
University of Milano-Bicocca
Monza, Italy
Member of the ESTRO urology focus group

Watch our on-site interview with the study co-author, Assistant Professor Camilla Thellenberg Karlsson: https://www.estro.org/Congresses/ESTRO-2025/ESTRO-2025-Interviews