NRG-GU003

Confirmatory

ForPostprostatectomy, pT2/3 pNX/0: detectable PSA, or undetectable with pT3/margin+

TL;DR5-yr: G3 GU AEs 13% HYPORT (62.5 Gy/25 fx) vs 3% COPORT (66.6 Gy/37 fx), p=0.003; EPIC scores and 5-yr BF (21% vs 18%) no different.

Why it mattersRadiation oncology

Physician-graded and patient-reported toxicity diverge: grade 3 cystitis (7% vs 0%) and hematuria (6% vs 0.7%) are higher with 62.5 Gy/25 fx, yet 5-yr EPIC urinary change (-8.0 vs -5.7, p=0.4) does not separate, on 56% EPIC compliance. The decision is prostate-bed hypofractionation with a disclosed bleeding-type GU risk, not a toxicity-neutral swap.

Monday clinic

In men after prostatectomy with pT2/3 pNX/0 disease and a detectable PSA, or an undetectable PSA with pT3 or margin-positive pT2, this supports prostate-bed HYPORT as an option alongside COPORT; it does not extend to pelvic nodal RT, which the source does not report.

12 details 3 trials watching

Design

Phase 3 trial, 296 men randomized (152 COPORT, 144 HYPORT). This is the 5-year report; median follow-up 7 years (range: 0 to 8). Blinding, stratification and site count are not stated in source.

Population & inclusion

Postprostatectomy men with either a detectable post-op PSA (source prints "=0.1 ng/mL") and pT2/3 pNX/0 disease, or an undetectable PSA (<0.1 ng/mL) with pT3 disease or pT2 with a positive surgical margin. The split between these two groups is not reported in source.

Radiotherapy

HYPORT: 62.5 Gy to the prostate bed in 25 fractions of 2.5 Gy. COPORT: 66.6 Gy in 37 fractions of 1.8 Gy, 48% more fractions. Pelvic nodal RT, technique and ADT use are not reported in source.

Endpoints

Primary (reported at 2 years): patient-reported GU and GI toxicity by EPIC, where HYPORT was noninferior. Secondary, reported here: EQ-5D quality of life, AEs, overall survival, prostate-cancer specific survival, and biochemical failure (PSA 0.4 ng/mL and rising; source prints the operator as "=").

Results

Arm-level figures are in the table. No difference in 5-yr EPIC bowel or urinary change scores, EQ-5D change, or 5-yr BF; 31 deaths, 4 (13%) due to prostate cancer.

Endpoint	HYPORT	COPORT	p
Grade 3 AEs	16% (23 men)	7% (11 men)	p=0.02
Grade 3 renal and urinary disorders	13% (18 men)	3% (5 men)	p=0.003
Noninfective cystitis	7%	0%	not reported
Hematuria	6%	0.7%	not reported
5-yr EPIC bowel change score	-2.0	0.6	p=0.1
5-yr EPIC urinary change score	-8.0	-5.7	p=0.4
EQ-5D change, baseline to 5 yr	0.0	-0.01	p=0.5
5-yr biochemical failure	21%	18%	p=0.3

Safety

Grade 3 AEs 16% (23 men) HYPORT vs 7% (11 men) COPORT, p=0.02, driven by grade 3 renal and urinary disorders, 13% vs 3% (p=0.003): noninfective cystitis 7% vs 0%, hematuria 6% vs 0.7%. No grade 4-5 RT-related AEs, one grade 3 stricture (COPORT), and time to grade 3 AEs did not differ (p=0.4).

vs leading data

Moderate hypofractionation for the intact prostate rests on large randomized trials such as CHHiP and PROFIT; the postoperative bed has lacked comparable randomized data. The authors state the grade 3 GU rates, including the excess with HYPORT, were consistent with contemporary series, which the source does not name.

Applies to

men after prostatectomy with pT2/3 pNX/0 disease and a detectable PSA, or an undetectable PSA with pT3 or margin-positive pT2, treated to the prostate bed

Does not represent pelvic nodal RT or any setting outside these eligibility groups, and ADT use is not reported in source.

Limitations

The patient-reported reassurance rests on 56% EPIC and 51% EQ-5D compliance at 5 years, with no account of who dropped out. BF is a secondary endpoint with no stated noninferiority margin, and p-values for the cystitis and hematuria differences are not given.

Discussion

HYPORT buys a shorter course at the cost of a physician-reported grade 3 cystitis/hematuria excess that patient-reported scores do not register. Biochemical control looks comparable (5-yr BF 21% vs 18%, p=0.3) but the trial was built around toxicity, so equivalence of disease control is suggested, not established.

Enrolment

CONSORT flow

Randomized296

↓

HYPORT

allocated 144

COPORT

allocated 152

Rationale

Phase 3 RCT with its primary PRO noninferiority endpoint met at 2 yr; 5-yr update agrees on PROs and BF but adds a physician-reported G3 GU excess. Abstract only.

Open questions

Does prostate-bed hypofractionation hold with pelvic nodal RT or concurrent ADT?
Ultrahypofractionated (SBRT) prostate-bed RT vs moderate hypofractionation

recruiting Post-prostatectomy Radiation Therapy--Moderate Versus Ultra-hypofractionated (Also Known as Stereotactic Body Radiation Therapy [SBRT]) Phase 2

n=136 · primary completion 2026-11 · randomized ph2 SBRT vs mod hypofx post-RP, 2-yr QOL

recruiting Salvage Stereotactic Body Radiotherapy of the Prostate Bed for Biochemical Recurrence After Radical Prostatectomy. Phase NA

n=284 · primary completion 2029-02 · randomized ph2/3 salvage bed SBRT vs SOC RT

not yet RIsk aDapted Stereotactic Radiotherapy vs. standarD of Care Radiotherapy in Patients With Prostate Cancer in the Adjuvant or saLvage sEtting With or Without Lymph Node Irradiation (RIDDLELN) - A Phase III Trial Phase 3

n=206 · primary completion 2031-09 · ph3 5-fx bed SBRT vs mild hypofx, PRO QOL non-inferiority
Do grade 3 cystitis/hematuria events keep accruing beyond 7-yr follow-up?

📚 Sources · 📄 1 paper

📄 PAPER M. K. Buyyounouski; M. Borges; R. C. Chen et al. · ASTRO 2026 Annual Meeting (2026-09)

Five-Year Results of a Phase 3 Trial of Hypofractionated vs. Conventional Postprostatectomy Radiotherapy: NRG Oncology GU003

doi article →

Abstract

ASTRO 2026 abstract 7 · CT 01 - Clinical Trials Session · 2026-09-27 · presented by Mark Buyyounouski, MD, MS, FASTRO Purpose/Objective(s): Biopsy Gleason 8–10 disease and MRI-suspected extracapsular extension identify men at high risk for adverse pathologic features at prostatectomy, observed in ~55–75% of cases. For a substantial subset, surgery alone is not curative, and PSA recurrence leads to radiotherapy (RT) to preserve curative intent. Conventionally fractionated postprostatectomy RT (COPORT) requires 37 fractions, 48% more than hypofractionated RT (HYPORT). In the primary 2-year analysis of this trial, HYPORT was noninferior to COPORT for patient-reported genitourinary and gastrointestinal toxicity. We now report longer-term 5-year results. Materials/Methods: A total of 296 men were randomized (152 to COPORT and 144 to HYPORT). Men with a detectable post-op PSA (=0.1 ng/mL) with pT2/3pNX/0 disease or an undetectable PSA (<0.1 ng/mL) with either pT3 or pT2 disease with a positive surgical margin were eligible. HYPORT was 62.5 Gy to the prostate bed in 25 fractions of 2.5 Gy. COPORT was 66.6 Gy in 37 fractions of 1.8 Gy. Patient-reported GU and GI toxicity was measured using the Expanded Prostate Index Composite (EPIC). Other secondary endpoints include quality of life as measured by EQ-5D, adverse events (AEs), overall survival, prostate-cancer specific survival, and biochemical failure (BF; PSA = 0.4 ng/mL and rising). Results: No grade 4–5 AEs related to RT were reported. Grade 3 AEs occurred in 7% (11 men) with COPORT and 16% (23 men) with HYPORT (p=0.02). Grade 3 renal and urinary disorders occurred in 3% (5 men) with COPORT and 13% (18 men) with HYPORT (p=0.003). This difference reflected higher rates of noninfective cystitis (0% vs 7%) and hematuria (0.7% vs 6%) with HYPORT vs COPORT. There was only one grade 3 urinary tract obstruction (stricture) on the COPORT arm. Time to grade 3 AEs did not differ between arms (p=0.4). At 5 years, EPIC compliance was 56% (58% in the COPORT arm and 55% in the HYPORT arm), while EQ-5D compliance was 51% in both arms. No significant differences were observed in 5-year EPIC bowel (0.6 vs -2.0; p=0.1) or urinary change scores (-5.7 vs -8.0; p=0.4) between COPORT and HYPORT. No significant difference was observed in EQ-5D score change from baseline to 5 years between COPORT and HYPORT (-0.01 vs 0.0; p=0.5). Median follow-up is 7 years (range: 0 to 8). A total of 31 deaths have been reported (14 on COPORT and 17 on HYPORT), 4 (13%) due to prostate cancer. There was no difference in BF (5-year rate: 18% for COPORT vs. 21% for HYPORT; p=0.3). Conclusion: The rates of grade 3 GU AEs (3% with COPORT and 13% with HYPORT), including the higher incidence with HYPORT and the predominance of cystitis and hematuria, were consistent with contemporary series. Despite a small absolute increase in physician-reported cystitis (7%) and hematuria (5%), HYPORT showed no differences in patient-reported outcomes compared with COPORT and comparable biochemical control, supporting HYPORT as an effective, patient-centered, and acceptable treatment approach.

📝 https://amportal.astro.org/sessions/ct-01-22948/five-year-results-of-a-phase-3-trial-of-hypofractionated-vs-conventional-postprostatectomy-ra-113319 10.1016/j.ijrobp.2026.06.009

Radiation Curative Phase 3 RCT Confirmatory ASTRO Annual Meeting 2026

The longer read

Moderate hypofractionation became standard for the intact prostate on the strength of large randomized trials such as CHHiP and PROFIT, but the postoperative bed is a different target. The bladder neck and the vesicourethral anastomosis sit inside the high-dose volume, and the randomized evidence for larger fractions there has been thin. GU003 is the randomized test of that extrapolation, and one design choice governs how to read it: the trial was built around patient-reported GU and GI toxicity, with HYPORT already shown noninferior at 2 years, and not around disease control.

The 5-year update splits according to who is doing the reporting. Physician-graded grade 3 renal and urinary events were 13% with HYPORT against 3% with COPORT (p=0.003), driven by noninfective cystitis and hematuria, while EPIC urinary change scores (-8.0 vs -5.7, p=0.4) did not separate. Both can be true at once. A bleeding episode that prompts intervention is graded 3 by the clinician without necessarily moving a urinary domain score measured years later. But the patient-reported side rests on 56% EPIC compliance at 5 years, and the abstract does not say whether men who had an event were as likely to return a questionnaire as men who did not. The reassurance from the PROs is softer than the p-values alone suggest.

The pattern of events is informative for an RT reader. Time to grade 3 AEs did not differ between arms (p=0.4), which reads as more events with HYPORT, not earlier ones. There were no grade 4-5 RT-related events, and the single grade 3 stricture occurred on the COPORT arm, so the specific fear that 2.5 Gy fractions would injure the anastomosis is not borne out here. What the larger fraction size appears to cost is bladder mucosal bleeding.

On disease control, a 5-year BF of 21% vs 18% (p=0.3) is a secondary endpoint in 296 men with no noninferiority margin stated in the source. A nonsignificant p-value is not evidence of equivalence, and with 31 deaths, 4 from prostate cancer, survival endpoints cannot discriminate between arms. The comparison is also against 66.6 Gy, so comparable control is relative to that dose and not to an escalated salvage regimen. Eligibility mixed adjuvant-type pts (undetectable PSA with adverse pathology) and salvage-type pts (detectable PSA). Since RADICALS-RT and RAVES moved practice toward early salvage, the detectable-PSA stratum is the one closest to current referrals, and the abstract does not report outcomes by that split.

What this changes is narrow and concrete: prostate-bed-only RT can be offered in 25 fractions, where COPORT's 37 fractions are 48% more, with a quantified grade 3 cystitis and hematuria risk to disclose. It leaves untouched whether the same holds with pelvic nodal fields or concurrent ADT, neither of which the source reports. The read would be wrong if PRO dropout was informative, or if bladder events keep accruing beyond the 7-year median follow-up.