FAQ: ASTRO guideline on hypofractionated radiation therapy for localized prostate cancer

The American Society for Radiation Oncology (ASTRO) has published an updated clinical practice guideline on the use of hypofractionated external beam radiation therapy (EBRT) for patients with localized prostate cancer.¹ The guideline replaces ASTRO's 2018 recommendations and reflects a considerably more mature evidence base, which shows that shorter-course radiation therapy can maintain cancer control and reduce overall treatment burden for patients receiving definitive EBRT.² It was developed by a multidisciplinary task force of radiation, medical oncologists, and urologic oncologists, as well as a medical physicist and a patient representative, in collaboration with the American Society of Clinical Oncology, the American Urological Association, the European Society for Radiotherapy and Oncology, and the Society of Urologic Oncology.

Among the key updates, the guideline recommends moderate hypofractionation over conventional fractionation across all risk groups and recommends ultrahypofractionation as a standard option for many patients, including those with intermediate-risk disease.

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

The following FAQs summarize the guideline's key recommendations, supplemented with additional insight from Morgan.

1. How does moderate hypofractionation differ from ultrahypofractionation?

Hypofractionated EBRT delivers radiation therapy in fewer treatment sessions than conventional fractionation, using a higher dose per treatment but maintaining a similar overall therapeutic effect.² Morgan explained that, historically, conventional fractionation delivered 2 Gy per fraction, which translated into a treatment course of roughly 8 weeks for patients with localized prostate cancer.

He noted that “prostate cancer has some tissue properties that make it particularly attractive for the use of hypofractionation.”

Moderate hypofractionation is typically delivered over 4 to 6 weeks, which Morgan described as approximately 20 to 28 fractions. Ultrahypofractionation, most commonly delivered as stereotactic body radiation therapy (SBRT), allows patients to complete treatment in 5 sessions over 1 to 2 weeks. According to Morgan, this approach has been made possible by advances in imaging and computing, including the use of MRI for target delineation, intensity modulation, and daily imaging before and during treatment.

2. What questions did the guideline task force set out to answer?

The task force addressed 5 key questions related to hypofractionated EBRT in localized prostate cancer, covering indications for moderate hypofractionation and ultrahypofractionation, appropriate dose-fractionation regimens, target volumes, and treatment planning and delivery techniques. Morgan added that the panel also considered how pretreatment characteristics should inform fractionation decisions, including which patients may be appropriate for either approach.

The recommendations are based on a systematic evidence review, supplemented by expert consensus where evidence was limited. Recommendations were graded for quality of evidence and strength of recommendation. Shared decision-making between physicians and patients is emphasized throughout, particularly where options vary by risk group, baseline urinary function, and patient preferences.

3. What evidence supports recommending moderate hypofractionation across all risk groups?

The guideline recommends moderate hypofractionation over conventional fractionation for patients receiving EBRT to the prostate, with or without treatment of the seminal vesicles, across all risk groups. This recommendation is supported by randomized trials that included more than 7000 patients, with long-term data showing comparable cancer control, adverse effect profiles, and quality of life.³

Morgan explained that, at the time of the 2018 guideline, median follow-up in many of the largest trials was approximately 5 years, and relatively few patients with high-risk disease had been enrolled. Since then, the evidence base has matured, with more than 10 randomized trials and published follow-up data of 10 years or longer for several of them.

“I think we can be that much more confident that moderate hypofractionation gives at least equivalent oncologic outcomes,” Morgan said. He added that the systematic review underpinning the guideline suggested a small overall improvement in biochemical control with moderate hypofractionation compared with conventional fractionation, with a similar late genitourinary (GU) and gastrointestinal (GI) adverse effect profile, and that companion patient-reported outcome data from several trials further support the recommendation.

4. Should patient characteristics influence whether moderate hypofractionation is used?

No. Moderate hypofractionation is recommended regardless of patient age, comorbidity, anatomy, or baseline urinary function. The guideline also states that decisions about androgen deprivation therapy should be made independently from the choice of fractionation regimen.

5. How does the guideline address elective pelvic nodal radiation therapy?

For patients receiving elective pelvic nodal radiation therapy, the guideline recommends moderate hypofractionation to the prostate with concurrent conventional or near-conventional radiation therapy to the pelvic lymph nodes, using a single-phase plan. According to Morgan, this new recommendation filled an evidence gap from 2018.

“There was a randomized trial that was done in Canada. It's called PCS-5, and that exclusively enrolled patients with high-risk disease where elective pelvic nodal radiotherapy was planned,” he said, adding that its findings were similar to those of the prostate-only trials.⁴

In contrast, ultrahypofractionated EBRT for elective pelvic nodal treatment is conditionally recommended only as part of a clinical trial.

6. Which patients are candidates for ultrahypofractionation?

Ultrahypofractionated EBRT is recommended as a treatment option for patients with low-risk localized prostate cancer who decline active surveillance and choose EBRT, as well as for patients with intermediate-risk disease receiving EBRT to the prostate and seminal vesicles. Ultrahypofractionated EBRT is conditionally recommended as a treatment option for patients with high-risk or very high-risk disease.

Morgan noted that no randomized trials of ultrahypofractionation had been published at the time of the 2018 guideline. Since then, 2 randomized trials have been published: HYPO-RT-PC, which compared ultrahypofractionation with conventional fractionation,⁵ and PACE-B (NCT01584258), which compared ultrahypofractionation with conventional fractionation or moderate hypofractionation.⁶ Both trials demonstrated noninferior oncologic outcomes. He emphasized that HYPO-RT-PC, which enrolled patients from approximately 2005 to 2015, predated SBRT techniques, whereas PACE-B used true SBRT.

Because PACE-B was conducted primarily in patients with intermediate-risk, grade group 2 (Gleason 3+4) disease, the evidence is strongest in that population. Morgan noted that the evidence is somewhat less strong for grade group 3 disease.

7. How should baseline urinary function inform the choice of fractionation?

For patients with significant baseline urinary symptoms, moderate hypofractionation is conditionally recommended over ultrahypofractionation, because ultrahypofractionation may increase the risk of treatment-related urinary adverse events in patients with significant lower urinary tract symptoms (LUTS).

Morgan noted that, in PACE-B, a slight excess in urinary adverse effects was observed with SBRT compared with moderate hypofractionation at 2 years after treatment, although this difference was not seen at 5-year follow-up.⁶ A post hoc analysis by the PACE-B investigators evaluated patient, clinical, treatment, dosimetric factors as potential predictors.⁷

“It seems that patients who have significant baseline lower urinary tract symptoms appear to be those that are at increased risk for GU [adverse] effects following SBRT,” Morgan said.

8. What dose-fractionation schedules are recommended?

For moderately hypofractionated EBRT, recommended dose schedules include 6000 to 6200 cGy in 20 fractions or 7000 cGy in 28 fractions. For ultrahypofractionated EBRT, a dose of 3625 to 4000 cGy in 5 fractions is conditionally recommended, and regimens using fewer than 5 fractions are not recommended outside of a clinical trial.

9. What target volumes does the guideline recommend?

Recommendations for target volumes vary by risk group and disease features. For patients with low-risk disease who decline active surveillance, treatment of the prostate alone is recommended. For patients with higher-risk disease, inclusion of at least part of the seminal vesicles is recommended or conditionally recommended depending on clinical risk, and a focal intraprostatic boost may be considered for selected patients with a dominant lesion visible on MRI.

10. What treatment planning and delivery practices does the guideline recommend?

Best practices emphasize precision and safety, including MRI-informed planning when appropriate, daily motion management, and intensity-modulated radiation therapy. The guideline also conditionally recommends intrafraction tracking for patients receiving ultrahypofractionated EBRT and discusses the use of rectal spacers as part of shared decision-making.

Overall, the evidence supports “contemporary image-guided, conformal treatment techniques to optimize target coverage and minimize toxicity.”¹ Morgan emphasized that improvements in radiation therapy track closely with advances in imaging.

“We are an imaging-oriented specialty in terms of how our treatment is planned and delivered,” he said.

11. What barriers need to be addressed to ensure equitable access to hypofractionated radiation therapy?

In national datasets, use of hypofractionated EBRT has varied by age, race, socioeconomic factors, and treatment setting, ASTRO noted. They added, “Because shorter-course treatment can reduce travel, time away from work, and other burdens associated with care, the guideline notes that equitable access to high-quality hypofractionated radiation therapy should remain a priority.”²

Morgan noted that SBRT is a more technically complex undertaking that requires expertise across multiple domains, including physics, radiation therapy, radiation oncology, and imaging. This expertise may be less likely to be present in rural or remote settings than in urban settings and may not be equitably distributed between academic and community centers. However, he described this barrier as one that can be addressed over time as technical expertise diffuses from high-volume academic centers.

He also emphasized that reducing an 8-week course to 5 fractions over approximately 2 weeks substantially reduces treatment burden for patients and has potential resource benefits for health care systems.

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REFERENCES

1. Morgan SC, Halthore A, Jia AY, et al. Hypofractionated Radiation Therapy for Localized Prostate Cancer: An ASTRO Clinical Practice Guideline. Practical Radiation Oncology. 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 November 9, 2026. https://www.astro.org/news-and-publications/news-and-media-center/news-releases/2026/astro-updates-guideline-on-shorter-course-radiation-therapy-for-localized-prostate-cancer

3. Hoffman KE, Voong KR, Levy LB, et al. Randomized Trial of Hypofractionated, Dose-Escalated, Intensity-Modulated Radiation Therapy (IMRT) Versus Conventionally Fractionated IMRT for Localized Prostate Cancer. J Clin Oncol. 2018 Oct 10;36(29):2943-2949. doi:10.1200/JCO.2018.77.9868

4. Niazi T, Nabid A, Malagon T, et al. Hypofractionated Dose Escalation Radiotherapy for High-Risk Prostate Cancer: the survival analysis of the Prostate Cancer Study-5 (PCS-5), a GROUQ-led phase III trial. Eur Urol. 2025;87(3):314-323. doi:10.1016/j.eururo.2024.08.032

5. Nilsson P, Gunnlaugsson A, Beckman L, et al. 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. Lancet Oncol. 2026 Mar;27(3):293-301. doi:10.1016/S1470-2045(25)00656-4

6. 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;391:1413-1425. doi:10.1056/NEJMoa2403365

7. Ratnakumaran R, Brand DH, Sasitharan A, et al. Exploring Factors Associated with Late Urinary Toxicity After Prostate Stereotactic Body Radiotherapy: Findings from the PACE-B Study. Eur Urol. 2026;89(1):71-79. doi:10.1016/j.eururo.2025.07.007