Prostate
All four reads are prostate RT: ultrahypofractionation durability and toxicity, moderate-hypofractionation dose selection, and salvage reirradiation for local radiorecurrence.
ARS Appropriate Use Criteria: Intraprostatic Recurrence
TL;DRPSMA-PET + mpMRI staging, mandatory biopsy, then curative-intent salvage reirradiation (โค6 fractions) preferred over ADT alone for local intraprostatic radiorecurrence.
Trials discussed
RTOG 9408FORECAST
Why it mattersRadiation oncology
For the salvage decision after definitive RT: biopsy is mandatory before reirradiation (positive post-RT biopsy carried HR 1.7 for BCR, RTOG 9408), and local salvage is preferred over ADT alone. Technique note: most reRT regimens run in โค6 fractions, and classic ADT (not ARSIs) is the preferred short-course radiosensitizer.
vs leading data
- RTOG 9408 post-hoc: positive post-RT biopsy (n=831) linked to HR 1.7 for BCR, independent of upfront ADT
8 details 5 trials watching
Methods
- ๐ ARS Genitourinary Appropriate Use Criteria; modified Delphi consensus across 4 topics: staging, biopsy, salvage selection, reRT technique
- ๐ Staging: PSMA-PET + mpMRI to exclude occult metastatic disease and map local extent before salvage
- ๐ Biopsy mandatory before local salvage, to avoid treating a radiographic recurrence that is only treatment effect (excess toxicity)
- ๐ ADT for radiosensitization only short-course; classic ADT preferred over novel hormonal agents (ARSIs)
Results
- ๐ Most reRT salvage regimens deliverable in โค6 fractions; whole-gland salvage toxicity called very tolerable
- ๐ FORECAST (n=155): mpMRI vs MRI-targeted biopsy for radiorecurrence (systematic biopsy reference)
Metric mpMRI MRI-targeted biopsy Sensitivity 94% (95% CI 88-98%) 92% (83-97%) Specificity 18% (7-35%) 75% (45-92%)
Critique
- โ ๏ธ Evidence limited to conventionally fractionated EBRT with pre-PSMA-PET-era workup; no prospective salvage RCT
Notes
- Local salvage preferred over noncurative hormonal manipulation alone; shared decision-making stressed
Open questions
- Prospective salvage reirradiation trials to define optimal regimen n=60 ยท primary completion 2024-11 ยท randomises salvage SBRT vs HDR brachy regimensrecruiting Stereotactic Re-irradiation of Local Recurrences of Prostate Cancer After Radiotherapy Phase 2n=55 ยท primary completion 2029-12 ยท phase 2 focal SBRT reRT, GU/GI toxicity endpointn=30 ยท primary completion 2032-01 ยท prospective salvage HDR partial-gland brachy
- Best focal vs whole-gland salvage after PSMA-PET-era staging n=100 ยท primary completion 2025-12 ยท focal partial-gland salvage brachy after prior RTactive Pilot Study of Whole Gland Salvage HDR Prostate Brachytherapy for Locally Recurrent Prostate Cancer Phase NAn=30 ยท primary completion 2027-08 ยท whole-gland salvage HDR brachy comparator arm
- Role of ADT duration/type as radiosensitizer in salvage reRT
๐ Sources ยท ๐ 1 paper
American Radium Society Appropriate Use Criteria for the Workup and Treatment of Local Intraprostatic Recurrence of Prostate Cancer Following Definitive Radiotherapy
HYDRA (MARCAP Consortium)
ForLocalised prostate cancer, definitive EBRT
TL;DRNo PFS difference for isodose or dose-escalated MHFRT vs CFRT (HR 0.92, 0.94); only dose-escalated adds late Gโฅ2 GI toxicity (OR 1.48).
Why it mattersRadiation oncology
The RT-actionable read is regimen choice, not whether to hypofractionate: dose-escalated MHFRT added late Gโฅ2 GI (OR 1.48) and bowel-QOL (OR 1.68) toxicity over CFRT with no PFS gain (HR 0.94), while isodose stayed null on both. Default to isodose 60Gy/20fx, not a dose-escalated hypofractionated schedule.
vs leading data
- Authors' bottom line: isodose (e.g. 60Gy/20fx) should be the standard MHFRT regimen for localized prostate
7 details 3 trials watching
Methods
- ๐ IPD meta-analysis of 7 randomised phase III CFRT vs MHFRT trials (MARCAP Consortium), data published pre-Dec 15 2023
- ๐ Isodose comparison: 3 trials, n=3454. Dose-escalated comparison: 4 trials, n=2426
- ๐ Median f/u 5.4y (IQR 4.6-7.2) isodose, 7.1y (IQR 5.7-8.4) dose-escalated
Results
- ๐ Isodose vs dose-escalated MHFRT, each pooled against CFRT (efficacy, physician toxicity, QOL)
Endpoint (vs CFRT) Isodose MHFRT Dose-escalated MHFRT PFS HR 0.92 (0.81-1.05) HR 0.94 (0.82-1.09) Late Gโฅ2 GU tox OR 1.16 (0.86-1.57) OR 1.20 (0.95-1.51) Late Gโฅ2 GI tox OR 1.30 (0.59-2.87) OR 1.48 (1.14-1.92) Urinary QOL decrement OR 1.03 (0.51-2.09) OR 1.57 (0.87-2.85) Bowel QOL decrement OR 0.76 (0.40-1.43) OR 1.68 (1.07-2.61) - ๐ Both MHFRT approaches non-inferior on PFS and neutral on GU; only dose-escalated crossed significance, and only for the GI/bowel axis
Critique
- โ ๏ธ Isodose vs dose-escalated is an indirect comparison across separate trial sets (different eras, populations, f/u), not a randomised head-to-head
- โ ๏ธ Efficacy endpoint is PFS only; no OS or metastasis-specific readout in source
Open questions
- Isodose vs dose-escalated MHFRT direct head-to-head trial
- OS and metastasis-free survival beyond PFS
- Ultra-hypofractionation (SBRT) vs moderate hypofractionation n=205 ยท primary completion 2026-06 ยท UH vs MH RT at iso-equivalent dose, HDR boostactive Radiation Hypofractionation Via Extended Versus Accelerated Therapy (HEAT) For Prostate Cancer Phase NAn=161 ยท primary completion 2027-02 ยท 5-fx SBRT vs 26-fx moderate hypofx, PSA failure EPn=503 ยท primary completion 2028-08 ยท moderate hypofx vs SBRT vs standard+boost arms
๐ Sources ยท ๐ 1 paper
Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement
10-yr SBRT for Prostate Cancer (Meier et al.)
ForLocalized low- and intermediate-risk prostate, ADT-naive
TL;DR10-yr RFS 90% (94% LR, 86% IR); late G3 GI/GU 1.4%/1.5%, no G4-5, after 40Gy/5fx prostate SBRT, no ADT.
Why it mattersRadiation oncology
Unfavorable-IR RFS was 77% vs 92% favorable IR (90% overall), all on SBRT monotherapy without ADT. The 40Gy/5fx robotic regimen holds for LR and favorable IR at 10y; the unfavorable-IR gap is where ADT or intensification still earns its place. Late G2+ GU 14% is the durable cost.
vs leading data
- Extends PACE-B (SBRT noninferior to conventional EBRT at 5 yr) to 10-yr durability
9 details 5 trials watching
Methods
- ๐ Phase 2 nonrandomized, N=310 (172 LR, 138 IR), 21 centers, median f/u 9 yr, treated 2008-2010
- ๐ Eligibility: LR (T1b-T2a, GS6, PSAโค10) / IR (GS7 & PSAโค10, or GS6 & PSA 10-20); prostate โค100cc
- ๐ No androgen suppression allowed, so the cancer-control result is RT-attributable, no hormonal confounding
Results
- ๐ 10-yr RFS 90%, OS 84%
- ๐ 10-yr relapse-free survival by risk group
- Low-risk: 94%
- Intermediate-risk: 86%
- Favorable IR: 92%
- Unfavorable IR: 77%
- ๐ 40 Gy in 5 fx (8Gyร5), noncoplanar robotic platform + real-time motion mgmt; ~EQD2 100 Gy (ฮฑ/ฮฒ=2)
- ๐ Late toxicity (CTCAE v3, >3mo)
- G3 GI/GU: 1.4% LR, 1.5% IR
- No grade 4-5 events
- G2+ GI 2.1%, G2+ GU 14%
Critique
- โ ๏ธ Single-arm, no randomized comparator; physician-reported CTCAE likely underreports late GU vs patient-reported
- โ ๏ธ Unfavorable IR is the weak spot: SBRT monotherapy without ADT may undertreat this subgroup
Open questions
- ADT benefit for unfavorable intermediate-risk treated with SBRT n=310 ยท primary completion 2025-12 ยท short-term ADT vs none, prostate SRT in UIRn=392 ยท primary completion 2030-04 ยท randomizes ADT+SBRT vs SBRT alone in UIR
- Optimal SBRT dose for unfavorable intermediate-risk prostate n=60 ยท primary completion 2025-12 ยท whole-prostate SBRT + SIB boost, int-unfavrecruiting Pilot Study of Dose Escalation in Prostate Radiotherapy Using the MR-Linac (DESTINATION-MRL) Phase NAn=20 ยท primary completion 2026-12 ยท MRI-directed dose-adapted 5fx SBRT, int riskrecruiting PRO-BOOST-LC: Whole-Gland Boost Strategies Versus SBRT Monotherapy in PSMA-Staged Localized and Locally Advanced Prostate Cancer Phase 2/3n=1200 ยท primary completion 2033-12 ยท SBRT monotherapy vs dose-escalated boost
๐ Sources ยท ๐ 1 paper
10-yr Survival and Toxicity Outcomes of Stereotactic Body Radiotherapy for Prostate Cancer: A Nonrandomized Clinical Trial
NRG-GU005
ForLocalized intermediate-risk prostate cancer
TL;DRCo-primary DFS superiority for SBRT not met (HR 1.38, p=0.13); bowel QoL favored SBRT (35% vs 44% MCID, p=0.034).
Reported via UroToday โ
Why it mattersRadiation oncology
The additive caution is efficacy: 3-yr biochemical failure doubled with SBRT (8% vs 4%, p=0.037) and 5-yr DFS numerically favored IMRT, sitting under a QoL-favorable headline. SBRT buys a real toxicity/QoL edge (Gโฅ3 GU 0.6% vs 2.5%) but no efficacy gain, so the SBRT-vs-IMRT choice turns on toxicity, not control.
vs leading data
- vs PACE-B: consistent lower urinary-incontinence QoL decline with SBRT vs MH-IMRT despite differing MCID definitions
8 details 5 trials watching
Methods
- ๐ Phase III international non-blinded RCT, N=698 (353 SBRT / 345 MH-IMRT), localized intermediate-risk prostate, 1:1, powered for SBRT superiority on co-primary DFS + EPIC-26 bowel/urinary HRQOL
- ๐ SBRT arm: 36.25 Gy in 5 fx (7.25 Gy/fx), 2-3 fx/wk; PTV margin 5mm radial, 3mm post/ant; fiducials + MRI fusion + daily IGRT mandated
- ๐ MH-IMRT arm: 70 Gy/28 fx or 60 Gy/20 fx; PTV margin 8mm except 5mm posteriorly. CTV = prostate ยฑ1cm proximal SV both arms
- ๐ Rectal spacer/manipulation used in ~55-56% of both arms (mostly SpaceOAR); associated with further superior EPIC bowel scores (LS mean -2.81, 95% CI -4.49 to -1.13, p=0.0011)
CONSORT flow
Randomized 698
โ
SBRT
allocated 353
MH-IMRT
allocated 345
Results
- ๐ Oncologic outcomes, SBRT vs MH-IMRT
Endpoint SBRT MH-IMRT Comparison 5-yr DFS 89% (85-92) 92% (89-95) HR 1.38 (0.91-2.09), p=0.13 3-yr biochemical failure 8% (5.2-11.0) 4% (2.3-7.0) p=0.037 5-yr OS 91% (85-95) 94% (90-97) p=0.66 - ๐ EPIC-26 minimal clinically important decline (MCID), SBRT vs MH-IMRT
Domain (timepoint) SBRT MH-IMRT p Bowel, 2yr (co-1ยฐ) 35% 44% 0.034 Urinary irritative/obstructive, 2yr (co-1ยฐ) 35% 34% 0.68 Bowel, 1yr 33% 46% 0.002 Sexual, 1yr 34% 44% 0.026 Urinary incontinence, 2yr 26% 35% 0.023 - ๐ Investigator-reported toxicity, SBRT vs MH-IMRT
Toxicity SBRT MH-IMRT p Gโฅ3 GU (TRAE) 0.6% 2.5% 0.04 Rectal hemorrhage, any grade 10.5% 17.3% 0.01 Fatigue, any grade 39.2% 50.8% 0.0025
Critique
- โ ๏ธ Trial's own goal was SBRT superiority; DFS futility bound crossed at interim and every efficacy endpoint numerically favored IMRT, so no efficacy case for SBRT here
Open questions
- Does SBRT's higher 3-yr biochemical failure translate to worse long-term clinical outcomes? active Stereotactic Body Radiation Therapy or Intensity-Modulated Radiation Therapy in Treating Patients With Stage IIA-B Prostate Cancer Phase 3n=692 ยท primary completion 2027-12 ยท phase 3 SBRT vs IMRT efficacy, stage IIA-Brecruiting Androgen Suppression Combined With Nodal Irradiation and Dose Escalated Prostate Treatment Phase 3n=710 ยท primary completion 2032-10 ยท phase 3 SBRT vs EBRT + brachy boost efficacyrecruiting PRO-BOOST-LC: Whole-Gland Boost Strategies Versus SBRT Monotherapy in PSMA-Staged Localized and Locally Advanced Prostate Cancer Phase 2/3n=1200 ยท primary completion 2033-12 ยท randomized SBRT monotherapy vs whole-gland boost
- Durability of SBRT QoL benefit and late toxicity beyond 2 years not yet Side Effects of Low Dose Rate Brachytherapy and Ultra-hypofractionated Radiotherapy in Low to Intermediate Risk Prostate Cancer Phase NAn=220 ยท primary completion 2030-12 ยท randomized ultra-hypofx SBRT late toxicity datarecruiting Vascular Optimized Radiotherapy Tuned to Critical Structures for Erectile Function Using High-Precision X-Ray Treatment Phase 3n=200 ยท primary completion 2035-12 ยท phase 3 SBRT, late GU/GI/sexual QoL
๐ Sources ยท ๐ 2 papers
ASTRO 2025: Co-Primary Results from NRG-GU005: A International Phase III Trial of SBRT versus Hypofractionated IMRT for Localized Intermediate Risk Prostate Cancer
Abstract
ASTRO 2025 results from NRG-GU005, international phase III trial of SBRT versus hypofractionated IMRT for localized intermediate risk prostate cancer.
๐ https://www.urotoday.com/conference-highlights/astro-2025/astro-2025-prostate-cancer/163512-astro-2025-co-primary-results-from-nrg-gu005-a-international-phase-iii-trial-of-sbrt-versus-hypofractionated-imrt-for-localized-intermediate-risk-prostate-cancer.html
ASTRO 2025: Quality of Life Results from NRG-GU005: A Phase III Trial of SBRT vs. Hypofractionated IMRT for Localized Intermediate Risk Prostate Cancer
Abstract
prostate cancer, Stereotactic Body Radiotherapy (SBRT), Hypofractionated Intensity-Modulated Radiation Therapy (IMRT), NRG-GU005, RTOG 0415 study.
๐ https://www.urotoday.com/conference-highlights/astro-2025/astro-2025-prostate-cancer/163502-astro-2025-quality-of-life-results-from-nrg-gu005-a-phase-iii-trial-of-sbrt-vs-hypofractionated-imrt-for-localized-intermediate-risk-prostate-cancer.html