Can shorter radiotherapy schedules deliver the same long-term outcomes as conventional treatment? The phase 3 HYPO-RT-PC trial provides one of the longest follow-ups to date, showing whether ultra-hypofractionation can match standard radiotherapy in both efficacy and safety for prostate cancer.
Title: Ultra-hypofractionated versus conventionally fractionated radiotherapy for localised prostate cancer (HYPO-RT-PC): 10-year outcomes of an open-label, randomised, phase 3, non-inferiority trial
Per Nilsson, Adalsteinn Gunnlaugsson, Lars Beckman, Anders Widmark, Per Fransson, Morten Hoyer, Magnus Lagerlund, Jon Kindblom, Bengt Johansson, Kirsten Björnlinger, Claes Ginman, Martha Olsson, Måns Agrup, Elisabeth Kjellén, Björn Zackrisson, Björn Tavelin, Lars Franzén, Harald Anderson, Camilla Thellenberg Karlsson.
Published in Lancet, March 2026
Background
Conventional radiotherapy for localized prostate cancer requires up to 8 weeks of treatment. Ultra-hypofractionation offers a much shorter schedule, but long-term data have been limited.
The HYPO-RT-PC trial was designed to determine whether a 7-fraction regimen could achieve comparable disease control without increasing late toxicity.
Methods
This phase 3, open-label, randomized non-inferiority trial was conducted across multiple centers in Sweden and Denmark. A total of 1200 men with intermediate- or high-risk localized prostate cancer were enrolled, with no use of androgen deprivation therapy permitted. Patients were randomly assigned to receive either ultra-hypofractionated radiotherapy, delivered as 42.7 Gy in seven fractions over 2.5 weeks, or conventionally fractionated radiotherapy, delivered as 78 Gy in 39 fractions over 8 weeks. The primary endpoint was failure-free survival, defined as biochemical failure, clinical progression, initiation of androgen deprivation therapy, or death from prostate cancer.
Results
After a median follow-up of just over 10 years, ultra-hypofractionated radiotherapy demonstrated sustained efficacy. Ten-year failure-free survival reached 72% in the ultra-hypofractionation group compared with 65% in the conventional group. The hazard ratio of 0.84 confirmed non-inferiority, with outcomes numerically favoring the shorter regimen.
Long-term toxicity profiles were comparable between the two approaches. Late grade 2 or higher genitourinary toxicity occurred in 28% of patients receiving ultra-hypofractionation and 30% of those receiving conventional treatment. Gastrointestinal toxicity rates were identical at 14% in both groups. No meaningful differences in late adverse effects were observed.
Key Findings
Ultra-hypofractionated radiotherapy maintained non-inferior long-term disease control compared with conventional fractionation, without increasing late toxicity. Despite delivering treatment in a much shorter timeframe, outcomes remained consistent over a decade of follow-up.
Conclusion
The 10-year results of the HYPO-RT-PC trial confirm that ultra-hypofractionated radiotherapy is a safe, effective, and practical alternative to conventional treatment for localized prostate cancer. These findings support its role as a standard-of-care option, offering substantial reductions in treatment duration while preserving long-term outcomes.
Written By Aren Karapetyan, MD