New ASTRO Guideline Backs Hypofractionated Radiation in Prostate Cancer

The American Society for Radiation Oncology (ASTRO) has published an updated clinical practice guideline on hypofractionated external beam radiation therapy (EBRT) for localized prostate cancer in Practical Radiation Oncology.¹ It recommends moderate hypofractionation over conventional fractionation for all risk groups. It also establishes ultrahypofractionation, typically delivered as stereotactic body radiation therapy (SBRT), as a standard treatment option for patients with low- and intermediate-risk disease. The guideline replaces ASTRO’s 2018 recommendations.²

For patients receiving EBRT to the prostate with or without the seminal vesicles, the task force strongly recommended moderate hypofractionation over conventional fractionation for all risk groups based on high-quality evidence. It also strongly recommended moderate hypofractionation regardless of age, comorbidity, anatomy, or urinary function, based on moderate-quality evidence. Since 2010, 11 randomized controlled trials involving more than 7000 patients have compared moderate hypofractionation with conventional fractionation, with follow-up exceeding 10 years in some. On meta-analysis, moderate hypofractionation reduced biochemical recurrence by 26% in relative terms. No trial showed superior biochemical control with conventional fractionation.

Ultrahypofractionated EBRT was strongly recommended as a treatment option in 2 groups, based on high-quality evidence:

• patients with low-risk disease who decline active surveillance;
• patients with intermediate-risk disease (high-quality evidence for Grade Group 2 and moderate-quality evidence for Grade Group 3).

Additionally, it was conditionally recommended for high-risk or very high-risk disease based on low-quality evidence.

The phase 3 PACE-B trial (NCT01584258) and phase 3 HYPO-RT-PC study (ISRCTN45905321) showed that ultrahypofractionation was noninferior to moderate hypofractionation or conventional fractionation for biochemical recurrence-free survival at 5 years.^3,4 In PACE-B, SBRT produced no differences in grade 2 or higher gastrointestinal toxicity or sexual adverse effects (AEs) vs the control arm. Medium-term grade 2 or higher genitourinary AEs were modestly higher with SBRT but resolved after approximately 30 months of follow-up.

For patients with significant baseline urinary symptoms, moderate hypofractionation was conditionally recommended over ultrahypofractionation. An International Prostate Symptom Score of 15 to 20 or higher is often used as the threshold, though the authors discouraged applying any cutoff rigidly. Ultrahypofractionation for elective pelvic nodal irradiation was conditionally recommended only within a clinical trial. Decisions about adding androgen deprivation therapy should be made independently of the fractionation regimen.

“SBRT has moved from a promising alternative to a standard treatment option for many patients with localized prostate cancer. These recommendations give clinicians clear direction on using shorter-course treatment safely while preserving the excellent outcomes patients expect from definitive radiation therapy,” said lead author Scott C. Morgan, MD, MSc, a radiation oncologist at The Ottawa Hospital Cancer Centre and associate professor in the Division of Radiation Oncology at the University of Ottawa in Canada, who chaired the guideline task force, in a news release.²

The guideline also sets out dose-fractionation regimens:

• Moderate hypofractionation: 6000 to 6200 cGy in 20 fractions, or 7000 cGy in 28 fractions (strong recommendation, high-quality evidence).
• Ultrahypofractionation: 3625 to 4000 cGy to the prostate in 5 fractions (conditional recommendation, moderate-quality evidence), preferably delivered on nonconsecutive days over approximately 2 weeks (conditional recommendation, low-quality evidence).
• Fewer than 5 fractions: not recommended outside a clinical trial (strong recommendation).
• Elective pelvic nodal irradiation: a single-phase plan, with moderate hypofractionation to the prostate and conventional or near-conventional fractionation to the pelvic nodes, is recommended.

The multidisciplinary task force addressed 5 key questions:

• indications for moderate hypofractionation;
• indications for ultrahypofractionation;
• dose-fractionation regimens;
• target volumes;
• treatment planning and delivery techniques.

The task force included radiation and medical oncologists, urologists, a medical physicist, and a patient representative. Recommendations were based on a systematic review conducted by the Agency for Healthcare Research and Quality and approved through a modified Delphi consensus process. The guideline was developed in collaboration with the American Society of Clinical Oncology (ASCO), the American Urological Association (AUA), the European Society for Radiotherapy and Oncology (ESTRO), and the Society of Urologic Oncology (SUO). It was endorsed by the AUA, ESTRO, SUO, and the Royal Australian and New Zealand College of Radiologists.

The authors added that, because shorter courses can reduce travel, time away from work, and overall treatment burden, ensuring equitable access to hypofractionated radiation remains a priority. Ongoing trials including NRG-GU009 (NCT04513717), NRG-GU010 (NCT05050084), NRG-GU013 (NCT05946213), and PACE-C (NCT01584258) are expected to clarify the role of ultrahypofractionation in higher-risk disease and its use alongside androgen deprivation therapy.

“Over the past decade, hypofractionation has transitioned from an alternative approach to the dominant form of definitive prostate EBRT in current use. The ability to safely shorten treatment duration while maintaining cancer control and [quality of life] represents a meaningful advance in patient-centered care and treatment delivery,” Morgan and coauthors wrote in the guideline.¹

References

1. Morgan SC, Halthore A, Jia AY, et al. Hypofractionated radiation therapy for localized prostate cancer: an ASTRO clinical practice guideline. Pract Radiat Oncol. Published online October 27, 2026. doi:10.1016/j.prro.2026.09.017
2. ASTRO updates guideline on shorter-course radiation therapy for localized prostate cancer. News release. American Society for Radiation Oncology. October 27, 2026. Accessed October 27, 2026. https://tinyurl.com/mppm8pt3
3. van As N, Griffin C, Tree A, et al. Phase 3 trial of stereotactic body radiotherapy in localized prostate cancer. N Engl J Med. 2024;391(15):1413-1425. doi:10.1056/NEJMoa2403365
4. Widmark A, Gunnlaugsson A, Beckman L, et al. Ultra-hypofractionated versus conventionally fractionated radiotherapy for prostate cancer: 5-year outcomes of the HYPO-RT-PC randomised, non-inferiority, phase 3 trial. Lancet. 2019;394(10196):385-395. doi:10.1016/S0140-6736(19)31131-6