In the NRG-GU005 trial, five-session SBRT improved bowel quality of life and the rate of serious urinary adverse events in intermediate-risk prostate cancer; but it did not achieve superiority in three-year disease-free survival and biochemical failure was more frequent.
SBRT, which reduces four to eight weeks of radiotherapy to a single week, increased comfort but could not demonstrate oncological superiority
19 August 2026 | Source: JAMA, Urology Times, Medscape, ASTRO 2025, NRG Oncology | Topic: Localized Prostate Cancer / Radiotherapy
KEY FINDINGS
- Trial: NRG-GU005 (NCT03367702), an international, open-label, randomized phase 3 trial covering 698 patients at 136 centres; the results were published in JAMA.
- Comparison: SBRT 36.25 Gy in 5 fractions versus moderately hypofractionated IMRT (MH-IMRT) 70 Gy in 28 fractions or 60 Gy in 20 fractions.
- Bowel quality of life favoured SBRT: Clinically meaningful deterioration (MCID) at year 2 was 34.9% versus 43.8% (p=0.03).
- No difference in urinary irritative/obstructive quality of life: 35.4% versus 33.7% (p=0.68).
- Serious urinary toxicity was lower with SBRT: Grade 3-4 genitourinary adverse events 0.6% versus 2.5% (p=0.04). Urinary incontinence (years 1 and 2) and sexual function (year 1) also favoured SBRT.
- Oncological superiority was not demonstrated: Three-year disease-free survival was 88.6% with SBRT and 92.1% with MH-IMRT; biochemical failure was 7.8% versus 4.2% (adjusted HR 1.82; 95% CI 1.01-3.27; p=0.046).
- Rectal spacer: Spacer use in both arms improved patient-reported bowel function.
Background: Why Do We Want to Reduce the Number of Fractions?
In localized prostate cancer, definitive radiotherapy forms, together with radical prostatectomy, the basis of curative treatment options. In classical conventional schedules treatment is spread over 8-9 weeks, and in moderately hypofractionated protocols over 4-6 weeks. Every session increases the patient's travel to the centre, loss of working time and psychological burden.
Stereotactic body radiotherapy (SBRT) delivers a high dose of radiation to a very small target volume under image guidance, typically in 5 fractions and within one to two weeks. The low α/β ratio of prostate tissue - that is, its relative sensitivity to a high dose per fraction - constitutes the radiobiological rationale for this approach. However, a high fraction dose also means a sharper risk for the bladder neck, the urethra and the anterior rectal wall.
What is MCID? The minimal clinically important difference is the threshold defining whether a change in a quality of life score is at a level perceptible by the patient. In NRG-GU005, the proportion of patients experiencing deterioration at the MCID level at year 2 was compared using the EPIC-26 questionnaire.
Study Design
| Parameter | Detail |
|---|---|
| Number of patients | 698 (SBRT n=353; MH-IMRT n=345), 136 centres |
| Patient profile | Previously untreated, localized intermediate-risk prostate cancer |
| Clinical stage | cT1-T2b |
| Risk definition | Gleason 3+4 (Grade Group 2) with PSA <20 ng/mL, or Gleason 3+3 (Grade Group 1) with PSA 10-20 ng/mL |
| Experimental arm | SBRT - 36.25 Gy in 5 fractions |
| Control arm | MH-IMRT - 70 Gy in 28 fractions or 60 Gy in 20 fractions |
| Quality of life instrument | EPIC-26 (urinary irritative/obstructive and bowel domains) |
| Primary endpoints | Rate of deterioration at the MCID level at year 2 and three-year disease-free survival |
Key Results
| Endpoint | SBRT (36.25 Gy / 5) | MH-IMRT | p |
|---|---|---|---|
| Urinary irritative/obstructive QoL - year 2 MCID | 35.4% | 33.7% | 0.68 |
| Bowel QoL - year 2 MCID | 34.9% | 43.8% | 0.03 |
| Grade 3-4 genitourinary adverse events | 0.6% | 2.5% | 0.04 |
| Three-year disease-free survival | 88.6% (95% CI 85.2-92.1) | 92.1% (95% CI 88.9-95.2) | - |
| Three-year biochemical failure | 7.8% | 4.2% | 0.04 |
Quality of life: two domains, two different results
In the urinary irritative/obstructive domain the difference did not reach statistical significance; that is, five-session high-dose delivery neither added a burden nor produced a clear gain in terms of voiding symptoms. In the bowel domain, by contrast, the picture favoured SBRT (an absolute difference of approximately 9 points). In addition, the use of a rectal spacer in both arms improved bowel function - a finding that underlines the value of rectal protection strategies whichever fractionation is chosen.
Oncological outcome: no superiority, but rather a warning signal
The adjusted hazard ratio was 1.82 (95% CI 1.01-3.27; p=0.046), and the fact that the lower bound of the confidence interval is very close to 1 indicates that this finding is borderline significant. This early signal, emerging ahead of the planned 5-year analysis, needs to be confirmed with longer follow-up.
Comparison With PACE-B: Does the Dose Difference Matter?
The other important phase 3 trial comparing SBRT with standard radiotherapy is PACE-B. In that trial, 874 patients (T1-T2) were randomized, and at a median follow-up of 74.0 months SBRT was found non-inferior to standard radiotherapy in terms of biochemical or clinical failure (95.8% versus 94.6%; HR 0.73; 90% CI 0.48-1.12; non-inferiority p=0.004). However, in PACE-B late grade 2 or higher genitourinary toxicity was more frequent in the SBRT arm (26.9% versus 18.3%; p<0.001).
The NRG-GU005 investigators note that the higher SBRT dose permitted in the PACE-B protocol may have contributed to the better PSA control observed in that trial. Reading the two trials together produces this picture: as the dose increases oncological control improves while urinary toxicity rises; when the dose is reduced, toxicity falls but biochemical control may weaken.
Dr Rodney J. Ellis, senior author of the trial, emphasises that longer follow-up and further studies are needed to determine whether the dose delivered to the whole gland should be raised to the PACE-B level, or whether equivalent outcomes could be reached while preserving low toxicity by applying a focused boost to high-risk regions under advanced imaging guidance.
Implications for Clinical Practice
1. SBRT is a legitimate option in the appropriately selected patient
In low and intermediate risk localized prostate cancer, five-session SBRT is a treatment that can be offered in the light of both PACE-B's non-inferiority data and NRG-GU005's toxicity profile. The reduction of treatment duration from 5-8 weeks to one week is a concrete gain for working patients, patients travelling long distances and elderly patients for whom frequent visits to the centre are difficult because of comorbidity.
2. But "shorter" is not automatically "better"
While SBRT provides an advantage in terms of comfort and early toxicity, it did not demonstrate superiority in biochemical control; on the contrary, it gave a borderline significant signal of disadvantage. This balance must be conveyed clearly when informing patients.
3. The distinction of risk group is critical
The NRG-GU005 population had a favourable intermediate-risk profile: cT1-T2b, Grade Group 1-2, PSA <20 ng/mL. These results cannot be transferred directly to high-risk disease, Grade Group 3 and above, or cases with suspected lymph node involvement.
4. A rectal spacer is valuable independently of fractionation
That spacer use improved bowel function in both arms supports taking rectal protection strategies into routine consideration.
5. A multidisciplinary decision is essential
In intermediate-risk localized prostate cancer, radical prostatectomy, definitive radiotherapy (conventional, hypofractionated or SBRT) and, in selected cases, active surveillance should all be put on the table together. The decision should be made jointly by urology, radiation oncology and medical oncology, taking into account the patient's age, life expectancy, voiding function, bowel history, expectations for sexual function and conditions of access to the centre.
Glossary
- SBRT: An advanced radiotherapy technique in which a high dose of radiation is focused on the target under image guidance in very few sessions (typically 5).
- MH-IMRT: An approach in which the dose per fraction is higher than the conventional schedule but lower than SBRT; usually completed in 20-28 sessions.
- EPIC-26: A standard 26-item patient-completed scale measuring quality of life in the urinary, bowel, sexual and hormonal domains.
- Biochemical failure: A rise in PSA more than 2 ng/mL above its lowest level (nadir) after radiotherapy; regarded as a harbinger of clinical recurrence.
- Rectal spacer: A gel-like, gradually absorbed spacer placed between the prostate and the rectum that reduces the radiation dose received by the rectum.
Conclusion
NRG-GU005 has established that five-session SBRT in localized intermediate-risk prostate cancer is a more comfortable but not oncologically superior option. The improvement in bowel quality of life and the reduction in serious urinary adverse events are meaningful and valuable in terms of patient experience. Against this, the higher rate of biochemical failure observed at three years calls for caution in treatment selection.
This picture once again makes visible the question at the centre of modern uro-oncology: where should we secure oncological safety while preserving quality of life by reducing treatment intensity? The answer lies not in a single protocol but in an individualised decision in which the right technique is chosen for the right patient. Five-year follow-up data and focused boost strategies under advanced imaging guidance will clarify this balance.
References
- Ellis RJ, Pugh SL, Yu JB, et al. Stereotactic body radiotherapy vs moderately hypofractionated IMRT for localized intermediate-risk prostate cancer: A randomized clinical trial. JAMA. 2026. doi:10.1001/jama.2026.12627
- Clarke H. SBRT improves multiple quality of life domains but not DFS vs MH-IMRT. Urology Times, 18 August 2026.
- Medscape. SBRT vs IMRT: Better for Bowel Symptoms, Not Cancer Control. August 2026.
- Ellis RJ, et al. Primary Results from NRG-GU005. Int J Radiat Oncol Biol Phys (ASTRO 2025 plenary).
- van As N, Griffin C, Tree A, et al. Phase 3 trial of stereotactic body radiotherapy in localized prostate cancer (PACE-B). N Engl J Med. 2024;391(15):1413-1425.
Important Note: This article has been prepared for scientific information purposes and does not constitute individual medical advice. The method used in the treatment of prostate cancer is determined by taking into account the stage of disease, Gleason score, PSA level, age, accompanying conditions and the patient's expectations. Always consult your physician regarding treatment decisions.
Dr. Murat Binbay - Urology, Uro-Oncology and Robotic Surgery
