Ultrahypofractionation of localized prostate cancer-an updated statement of the prostate cancer working group of the German Society of Radiation Oncology (DEGRO)

Background Prostate cancer (PCa) is the most frequently diagnosed malignancy among men in Germany. Radiation therapy is a standard treatment for localized PCa. Ultrahypofractionation (UHF) delivers high doses in fewer fractions, thus offering a time-efficient option compared to traditional standard fractionation lasting for 7-8 weeks. The German Society of Radiation Oncology (DEGRO) expert panel statement provides an updated evaluation of randomized trials with at least 5 years of follow-up. Methods The members of the DEGRO PCa working group performed a literature search for randomized trials of UHF for localized prostate cancer in March 2025. The analysis included phase III randomized trials with at least 5 years of follow-up: HYPO-RT-PC, PACE-B, and a proton therapy trial. Results All trials demonstrated noninferiority of UHF radiotherapy in maintaining disease control. The HYPO-RT-PC trial reported a 5-year failure-free survival rate of 84% in both treatment groups and PACE-B reported noninferiority with a 95.8% rate in the SBRT group compared to 94.6% in the control group. Acute urinary and bowel toxicities were more pronounced in UHF arms but resolved over time. Late urinary toxicity was significantly higher in SBRT patients (26.9% vs. 18.3%, p < 0.001, PACE-B). Proton SBRT showed slightly increased toxicity measured by sexual and urinary EPIC. Conclusion Ultrahypofractionation represents an effective alternative to conventional fractionation in low- to intermediate-risk PCa with similar oncologic outcomes. However, physicians should inform their patients-particularly those with suboptimal urinary function-about an increased risk for GU toxicity.