Meta-analysis
STAMPEDE (abiraterone ± enzalutamide, high-risk non-metastatic) NCT00268476
ForHigh-risk M0 prostate: node+ or ≥2 of T3-4/Gleason 8-10/PSA≥40
TL;DRMFS HR 0.53 (6yr 82% vs 69%) and OS HR 0.60 adding 2yr abiraterone to ADT in high-risk M0 prostate (85% also had RT).
The RT read: abiraterone sits on top of definitive ADT+RT (74Gy/37fx to prostate+SV in the 85% who got RT), not RT vs no-RT. It moves systemic intensification for the high-risk M0 pt you're already irradiating; enzalutamide adds nothing over abiraterone (interaction HR 1.02, p=0.91).
8 details 2 trials watching
Pooled meta-analysis of two open-label phase 3 RCTs within the STAMPEDE platform, 113 UK/Swiss sites, N=1974, randomized 1:1. Median follow-up 72 mo (60-84).
High-risk non-metastatic disease: node-positive, or if node-negative ≥2 of T3/T4, Gleason 8-10, PSA ≥40; or high-risk relapse. Median age 68, median PSA 34; 39% node-positive.
Abiraterone 1000mg + prednisolone 5mg daily for 2yr added to 3yr ADT; the second trial's combination arm also received enzalutamide 160mg. Control = ADT alone.
RT planned in 85% (1684/1974): 74Gy/37fx to prostate + seminal vesicles or hypofractionated equivalent. Mandated if node-negative, encouraged if node-positive.
Primary: metastasis-free survival. Secondary: OS, prostate cancer-specific survival, biochemical failure-free survival, PFS, and toxicity.
Adding enzalutamide to abiraterone gave no extra MFS benefit (interaction HR 1.02, p=0.91), with no between-trial heterogeneity.
Open-label design, though MFS/OS are hard endpoints less prone to ascertainment bias. Pooled across two platform trials; no radiotherapy-treated subgroup HR reported in the source excerpt.
Two randomised phase 3 trials pooled; MFS primary hit (HR 0.53) with concordant OS benefit at 72mo, applicable high-risk M0 population. Adding enzalutamide gave no extra benefit.
In high-risk M0 prostate (node+, or ≥2 of T3-4/Gleason 8-10/PSA≥40) going to definitive ADT+RT, this supports adding 2yr abiraterone; it does not extend to lower-risk localized disease, and adding enzalutamide buys nothing.
- Optimal duration of abiraterone (2yr fixed used here)
- Whether benefit holds when radiotherapy is omitted
- Long-term OS and cure fraction beyond 72 months recruiting A Study of Metastases Free Survival With Saruparib vs Placebo Added to a Standard RT/ADT in Men With High-risk Prostate Cancer With a BRCA Mutation Phase 3n=700 · primary completion 2033-03 · MFS endpoint, high-risk localised, 2033 readoutrecruiting Abi/Pred + ADT vs ADT in PSMA-Positive, Conventionally Node-Negative Prostate Cancer Phase 2n=140 · primary completion 2033-04 · abi added to ADT+RT in localised, 2033 readout
📚 Sources · 📄 1 paper
HYDRA
ForLocalised prostate cancer, definitive EBRT, moderately hypofractionated
TL;DRNo PFS difference vs conventional RT for either MHFRT type, but dose-escalated MHFRT alone raised late G2+ GI + bowel-QoL decrement; isodose 60/20 clean.
The split that matters: dose-escalated MHFRT raised late G2+ GI (OR 1.48, p=0.0035) and patient-reported bowel decrement (OR 1.68, p=0.023), while isodose 60/20 stayed clean on every toxicity and QoL axis at equal PFS. Escalating buys no efficacy, so default to isodose MHFRT.
8 details 5 trials watching
IPD meta-analysis of 7 phase 3 RCTs (MARCAP consortium) of CFRT vs MHFRT. Primary efficacy endpoint PFS; co-primary toxicity late G2+ GU and G2+ GI; co-primary PRO urinary/bowel QoL decrement. Two prespecified strata: isodose vs dose-escalated MHFRT.
Localised prostate cancer. CFRT arm required modern dose (≥70 Gy in 2 Gy equivalents); trials lacking published IPD efficacy or late-toxicity data excluded. 3454 pts across 3 isodose trials, 2426 pts across 4 dose-escalated trials.
Isodose MHFRT exemplified by 60 Gy in 20 fractions; dose-escalated MHFRT schedules pooled (specific fractionations not given in source). Median follow-up 5.4 y (isodose) and 7.1 y (dose-escalated).
Efficacy equivalent to CFRT for both strata. The only toxicity separations were in the dose-escalated arm, late G2+ GI and bowel QoL, not isodose (see table).
Reinforces isodose 60/20 (CHHiP-type) as the standard MHFRT regimen and argues against dose-escalating hypofractionated schedules, which buy no efficacy but cost bowel toxicity.
Physician-scored late toxicity carries grading subjectivity, though PRO data corroborate the bowel signal. Dose-escalated stratum pools heterogeneous fractionation; longer follow-up needed to confirm late-toxicity divergence.
IPD meta-analysis of 7 phase 3 RCTs consolidating isodose 60/20 as standard MHFRT; reinforces current practice, no efficacy gained by dose-escalating.
In localised prostate cancer choosing moderate hypofractionation, this supports isodose 60 Gy/20 fx over dose-escalated hypofractionated schedules; it does not speak to SBRT/ultrahypofractionation or node-positive disease.
- Late-toxicity divergence with follow-up beyond 7 years
- Whether ultrahypofractionation (SBRT) shares the dose-escalation toxicity penalty n=54 · primary completion 2027-02 · 2-fx MR-linac dose de-escalation vs bowel/GU toxicityn=42 · primary completion 2028-01 · 40Gy/5fx SABR, GI/GU vs historical rates
- Optimal dose-escalated schedule if used in higher-risk disease active Comparative Study of Radiotherapy Treatments to Treat High Risk Prostate Cancer Patients Phase 3n=307 · primary completion 2026-12 · HDR boost vs hypofx dose-escalation, high-riskrecruiting Hypofractionated Radiotherapy With a Focal Microboost for High-Risk and Locally Advanced Prostate Cancer Phase 2n=46 · primary completion 2029-01 · hypofx focal microboost, high/very-high riskrecruiting Tumor-directed Radiation Therapy for Patients With the Highest Risk Category of Localized Prostate Cancer Phase NAn=76 · primary completion 2031-09 · ultra-hypofx boost + nodal RT, very high-risk
📚 Sources · 📄 1 paper
Abstract
WOLVERINE
ForOligometastatic prostate cancer (≤5 mets), predominantly castration-sensitive
TL;DRPFS HR 0.44, rPFS HR 0.60 favor MDT added to SOC in oligomet prostate; OS HR 0.63 non-sig (p=0.051).
Surfaced from a review's discussed trials
MDT here is predominantly SBRT, and the RT-attributable read is that benefit held in the sensitivity analysis excluding observation-only-SOC trials (PFS HR 0.46, CRFS HR 0.46), so MDT adds on a systemic backbone, not just vs nothing. OS stayed non-significant (HR 0.63, p=0.051): the gain is delaying progression and castration resistance, not proven survival.
7 details 5 trials watching
IPD meta-analysis (PROSPERO CRD42023479078) of 7 phase 2 RCTs; the primary MDT-efficacy analysis pooled 6 trials randomizing 472 men to MDT+SOC (n=248) vs SOC (n=224). Median follow-up 40.7 mo (IQR 25.6-53.7).
Oligometastatic (up to 5 mets) prostate cancer; 65% castration-sensitive (n=375), ARTO entirely CRPC and EXTEND baskets CRPC-enriched. 85.5% (n=491) had prior definitive local therapy; median PSA 1.9 both arms.
MDT is delivered per each component trial (EXTEND, STOMP, ORIOLE, ARTO, COMET-SABR), predominantly SBRT-based. Dose, fractionation, target volume, and modality breakdown are not reported in this meta-analysis, so the technique-transfer question can't be answered from source.
Coprimary: PFS and OS. Secondary: rPFS and castration resistance-free survival (CRFS).
MDT plus SOC improved PFS, rPFS, and CRFS across both trial- and patient-level analyses; overall survival did not reach significance (effect sizes in the table above).
STOMP and ORIOLE (observation-controlled SBRT trials) drove the early MDT signal; this pooled IPD extends the PFS/CRFS benefit across 6 trials and shows it persists on a systemic-therapy backbone in the observation-excluded sensitivity analysis.
All 7 component trials are phase 2 with non-blinded randomization ('some concerns' RoB) and open-label PSA-driven endpoints. OS non-significant (p=0.051). SOC arm slightly older (71 vs 68) and more often on 2nd-gen ARPI (59.8% vs 50.4%).
IPD meta-analysis of 6 phase-2 non-blinded RCTs; PFS/rPFS/CRFS clearly hit but OS non-significant. Reinforces the emerging MDT-for-oligomet signal (STOMP, ORIOLE), doesn't establish survival.
In castration-sensitive oligometastatic prostate cancer, up to 5 mets and mostly post definitive local therapy, the pooled evidence supports MDT plus SOC to delay progression and castration resistance; it does not establish a survival benefit nor extend to the CRPC-predominant setting.
- Does MDT extend overall survival in oligometastatic prostate cancer? active Prostate-cancer Treatment Using Stereotactic Radiotherapy for Oligometastases Ablation in Hormone-sensitive Patients Phase 3n=550 · primary completion 2026-06 · phase 3 SBRT + SOC vs SOC in oligomet HSPCrecruiting Veterans Affairs Seamless Phase II/III Randomized Trial of STAndard Systemic theRapy With or Without PET-directed Local Therapy for Oligometastatic pRosTate Cancer Phase 2/3n=464 · primary completion 2026-09 · phase 2/3 systemic ± PET-directed local therapy
- Optimal MDT (SBRT) target volume and dose across trials recruiting HIghly MetAstatic Life Prolonging Therapy-Resistant Prostate Cancer: Role of Stereotactic Radiotherapy for Bone and Lymph Node Metastases (HIMARS) Phase NAn=18 · primary completion 2028-05 · phase 1 max-tolerated-volume SBRT escalationrecruiting OligoCare TwiCs (Trials Within Cohorts) Trial Comparing Acute Toxicity in Single-fraction vs Multiple-fraction SBRT for Metastasis-directed Treatment (SPRINT) Phase NAn=302 · primary completion 2029-02 · single- vs multi-fraction SBRT for mets
- MDT benefit in CRPC vs castration-sensitive disease recruiting Metastasis-directed Therapy in Oligoprogressive Castration-refractory Prostate Cancer Phase 3n=246 · primary completion 2029-01 · phase 3 MDT in oligoprogressive CRPC
📚 Sources · 📄 1 paper
Abstract
FIRESTORM
ForHigh-risk meningioma: WHO grade 2 STR or recurrent, postop RT
TL;DR5-yr PFS 65.8% vs 38.8% favoring dose-escalated RT (BED ≥79.2 Gy), HR 0.40; OS not improved.
The trade-off is the actionable read: escalating to BED ≥79.2 Gy (≈66 Gy/33 fx) roughly doubled 5-yr PFS (65.8% vs 38.8%) but tripled any-grade radionecrosis (33.9% vs 13.2%), with severe RN unchanged (5.1% vs 3.2%) and no OS gain. Benefit was largest after subtotal resection.
9 details 3 trials watching
Individual patient-level meta-analysis pooling 7 institutions, N=248 (59 DE-RT, 189 SD-RT). Retrospective, non-randomized; compared by Kaplan-Meier, Cox multivariable, and IPTW propensity analysis.
High-risk meningioma: 75.8% WHO grade 2, 41.5% recurrent (grade 3 the remainder), 75.2% subtotal resection.
DE-RT defined as biologically effective dose ≥79.2 Gy (equivalent 66 Gy/33 fx); SD-RT comparator conventionally fractionated 59.4 Gy/33 fx or 60 Gy/30 fx. Mixed photon/carbon vs photon-alone DE-RT showed no PFS difference (81.3% vs 92.0% at 3y, P=.34).
Primary: progression-free survival, DE-RT vs SD-RT. Also overall survival and CNS radionecrosis.
OS not improved despite the PFS gain: 5-yr OS 83.8% vs 68.4% (P=.056 UVA), non-significant on MVA (HR 0.66, P=.27) and IPTW (HR 0.77, P=.42).
| Endpoint | DE-RT | SD-RT |
|---|---|---|
| 3-yr PFS | 86.4% | 55.6% |
| 5-yr PFS | 65.8% | 38.8% |
| Adjusted HR (MVA) | 0.40 (0.24-0.69), P=.001 | ref |
| IPTW HR | 0.45 (0.24-0.83), P=.01 | ref |
| Radionecrosis | DE-RT | SD-RT |
|---|---|---|
| Any grade | 33.9% (20/59) | 13.2% (25/189) |
| Grade 3+ | 5.1% | 3.2% |
Any-grade radionecrosis higher with DE-RT (33.9% vs 13.2%, P=.001) but grade 3+ similar (5.1% vs 3.2%); most RN was low-grade.
Standard-dose postoperative meningioma RT (RTOG-0539 high-risk 60 Gy, EORTC-22042 60 Gy) sits at/below this cohort's SD-RT arm; the dose-response signal here motivates the ongoing randomized escalation question.
Retrospective non-randomized pooling: DE-RT allocation confounded, IPTW mitigates but cannot fully adjust. PFS gain without OS benefit; prior-RT and grade imbalance across arms.
Retrospective non-randomized IPD pooling; DE-RT allocation confounded despite IPTW. PFS-only gain, no OS benefit. Signal supports escalation but needs randomized confirmation.
In high-risk meningioma (WHO grade 2, subtotally resected or recurrent) receiving postoperative RT, this supports a higher dose (BED ≥79.2 Gy) for local control; it does not extend to gross-totally-resected grade 1 disease or establish an OS benefit.
- Randomized confirmation of dose-escalated RT for high-risk meningioma active A Trial of Increased Dose Intensity Modulated Proton Therapy (IMPT) for High-Grade Meningiomas Phase NAn=21 · primary completion 2027-08 · increased-dose IMPT for high-grade meningioman=90 · primary completion 2028-12 · proton dose-escalation, 5y RFS in grade II/III
- Whether the PFS gain translates to an OS benefit
- Optimal escalation technique and dose (photon vs particle) recruiting Long-term Cognitive and Functional Impact of Proton-therapy or Modern Fractionated Radiotherapy in Cavernous Sinus Meningioma: An Open-label Randomized 1:1 Phase III Study Phase NAn=160 · primary completion 2032-02 · randomized proton vs photon RT, phase 3
📚 Sources · 📄 1 paper
Abstract
NRG/RTOG 9804 + E5194 Combined Analysis
ForGood-risk DCIS (low/int grade, ≤2.5cm, ≥3mm margins), lumpectomy without RT
TL;DR15-yr IBR 11.4% vs 19.0% with vs without tamoxifen in RT-omitted good-risk DCIS; MVA HR 0.54, invasive-IBR HR 0.43.
Tamoxifen's benefit here concentrates on invasive IBR (HR 0.43, p=0.0042), not DCIS-IBR (p=0.089), offsetting the recurrences that carry survival weight. But 15-yr IBR stays 11.4% even with tamoxifen, and no arm tests RT, so this informs the omit-RT-plus-endocrine path, not RT vs tamoxifen.
7 details 4 trials watching
Ancillary exploratory analysis pooling the non-RT arm of NRG/RTOG 9804 with the good-risk cohort of ECOG-ACRIN E5194. N=878 (317 + 561), median follow-up 14.85 yr.
Good-risk DCIS: low or intermediate grade, ≤2.5 cm, margins ≥3 mm, lumpectomy without RT. Median age 59. Tamoxifen users skewed toward negative re-excision and pathologic size ≤5 mm.
Tamoxifen optional and non-randomized, used by 43.1% overall (65.6% in 9804, 30.3% in E5194).
No RT in either cohort by design; this characterizes the RT-omitted good-risk population, not an RT comparison.
IBR overall, invasive IBR, DCIS-IBR, contralateral breast event, OS. Fine-Gray competing-risk models, univariate plus multivariable.
NSABP B-24 randomized tamoxifen after lumpectomy plus RT and cut breast events; this extends the tamoxifen signal to the RT-omitted good-risk setting, though non-randomized.
Tamoxifen not randomized; users differed on prognostic factors (re-excision, size), so residual confounding is likely. Exploratory combined dataset, not a prespecified endpoint.
| Endpoint | HR (95% CI) | p |
|---|---|---|
| Any IBR | 0.54 (0.35-0.83) | 0.0045 |
| Invasive IBR | 0.43 (0.24-0.77) | 0.0042 |
| Group | 15-yr IBR (95% CI) |
|---|---|
| Tamoxifen | 11.4% (7.9-15.5) |
| No tamoxifen | 19.0% (15.3-22.9) |
Non-randomized optional tamoxifen compared within a post-hoc combined dataset; users differed on prognostic factors. Consistent with randomized NSABP B-24 signal but confounded here.
For good-risk DCIS where RT is already being omitted, this supports endocrine therapy to reduce invasive IBR; it does not test whether tamoxifen substitutes for RT.
- Whether endocrine therapy can substitute for RT in good-risk DCIS not yet Assessment of Biosignature Classification of DCIS for RadioTherapy Benefit Post Lumpectomy (ABCD RT) Phase 3n=5270 · primary completion 2039-07 · phase 3 RT omission in biosignature-low DCIS
- Aromatase inhibitor vs tamoxifen in RT-omitted good-risk DCIS recruiting DCIS: RECAST Trial Ductal Carcinoma In Situ: Re-Evaluating Conditions for Active Surveillance Suitability as Treatment Phase 2n=400 · primary completion 2028-11 · DCIS trial with tamoxifen vs AI arms
- Which good-risk DCIS pts can omit both RT and endocrine therapy active Comparing an Operation to Monitoring, With or Without Endocrine Therapy (COMET) Trial For Low Risk DCIS Phase NAn=997 · primary completion 2024-06 · active monitoring vs surgery, low-risk DCISn=2500 · primary completion 2034-02 · active surveillance vs standard, low-risk DCIS
📚 Sources · 📄 1 paper
Abstract
INRT-AIR & DARTBOARD pooled analysis
ForOropharynx/larynx/hypopharynx HNSCC, stage I-IVB, excl T1-2N0 larynx
TL;DR5-yr solitary elective nodal recurrence 0% with ENI omission across 117 pts; 5-yr OS 87%, PFS 74%.
The failure pattern is what matters: solitary elective nodal recurrence was 0% at 5 yrs while 3-yr local recurrence ran 9.5% and distant 11%, so the residual risk sits in the primary and systemically, not in the uncovered elective levels. Node selection was AI-assisted off PET/CT plus neck CT, which gates whether the volume reproduces outside these trials.
| Endpoint | Timepoint | Value |
|---|---|---|
| Solitary elective nodal recurrence | 5-year | 0% |
| Local recurrence | 3-year | 9.5% |
| Regional recurrence | 3-year | 4.3% |
| Distant metastasis | 3-year | 11% |
| Overall survival | 5-year | 87% |
| Progression-free survival | 5-year | 74% |
| Composite MDADI (mean) | 12 months | 84.9 |
+1 more figure
10 details 5 trials watching
Patient-level pooled analysis of two prospective trials of involved nodal RT, INRT-AIR and DARTBOARD. N=117, median follow-up 3.4 years. No randomised ENI comparator arm.
HNSCC of oropharynx, larynx, and hypopharynx, stage I-IVB, excluding T1-2N0 larynx. Completed PET/CT and neck CT required for entry.
INRT omits elective nodal irradiation, treating involved nodes only, with an artificial-intelligence model assisting identification of suspicious lymph nodes. Dose, fractionation, and margin not reported in source.
5-yr solitary elective nodal recurrence 0%. 3-yr cumulative incidence: local 9.5%, regional 4.3%, distant 11%. 5-yr OS 87%, PFS 74%.
Mean composite MDADI 84.9 at 12 months, with no significant decline after treatment. No late G3+ toxicity, xerostomia, or feeding-tube rates reported in source.
Pooled single-arm data with no ENI control, so the 0% solitary elective recurrence carries no randomised contrast. Median follow-up 3.4 yrs underpins 5-yr estimates, and the AI nodal-selection step is not externally reproduced.
The dosimetric case for INRT rests on OAR sparing, but the only patient-reported outcome here is swallowing (MDADI 84.9), with no xerostomia or dysphagia comparison against ENI. Authors state randomized evidence is required before non-trial implementation.
Pooled single-arm prospective cohorts, N=117, no randomised ENI comparator; presenters explicitly require randomised evidence before non-trial use.
In PET/CT-staged oropharynx, larynx, or hypopharynx HNSCC (excluding T1-2N0 larynx) being planned for definitive chemoRT, this supports enrolling on an INRT trial rather than omitting elective nodal coverage off-protocol, and it does not speak to node-positive necks staged without PET/CT.
- Does INRT reduce late toxicity vs ENI in a randomized comparison? recruiting Dose De-escalation and Sentinel LN Mapping Driven Radiotherapy of Contralateral Neck in Ipsilateral Node Positive HNSCC Phase NAn=147 · primary completion 2027-01 · tests contralateral elective volume + dose reductionrecruiting Personalized Elective Neck Irradiation Guided by Sentinel Lymph Node Biopsy in Larynx and Pharynx Cancer. The PRIMO Study. Phase 3n=242 · primary completion 2029-12 · phase 3 SLNB-guided vs standard ENI, 242 pts
- Is the AI nodal-selection step reproducible outside these two trials? not yet SPECT-CT Guided ELEctive Contralateral Neck Treatment in Lateralized Oropharyngeal Cancer Phase NAn=128 · primary completion 2030-04 · SPECT-CT lymphatic mapping to select elective volume
- Does INRT hold for HPV-negative and oral cavity primaries? recruiting Personalized Neck Radiation Therapy Directed by Sentinel Lymph Node Biopsy for the Treatment of Oral Cavity Squamous Cell Carcinoma, PRECEDENT Trial Phase 2n=50 · primary completion 2030-07 · SLNB-directed neck RT in oral cavity SCC, cT1-4arecruiting Comparing Sentinel Lymph Node (SLN) Biopsy With Standard Neck Dissection for Patients With Early-Stage Oral Cavity Cancer Phase 2/3n=686 · primary completion 2031-04 · SLNB vs elective neck dissection, early oral cavity
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Day FOUR of #ESTRO26 Coverage by OncoAlert 🚨
— OncoAlert (@OncoAlert) May 18, 2026
Omission of elective nodal irradiation in HNSCC: long-term results and patient-level pooled analysis from 2 prospective trials (INRT-AIR & DARTBOARD)
Presenter Sympascho Young 🇺🇸
A patient-level pooled analysis of 117 patients… pic.twitter.com/KaaT70nSNH
Multinational HCC EBRT IPD Cohort
ForVery early / early-stage HCC (BCLC-0 to A), Child-Pugh A predominant
TL;DRMedian OS 6.8y BCLC-0 and 4.6y BCLC-A across 4,913 EBRT-treated HCC pts, comparable to resection/ablation.
The treatment-naive BCLC-0 arm is the RT-relevant cell: median OS not reached (95% CI 8.6 to NR), i.e. first-line EBRT in a truly untreated very-early cohort, not salvage after failed ablation. Ablative dose independently predicted lower mortality, so this moves the dose-selection and BCLC-algorithm-placement decisions.
9 details 3 trials watching
Systematic review (search date December 15, 2022) of EBRT series meeting prespecified HCC technical standards and reporting OS, followed by individual patient data solicitation from corresponding authors. Kaplan-Meier OS and RMST stratified by BCLC stage and treatment status; random-effects Cox for covariates.
N=4,913 EBRT-treated HCC pts across a multinational author network, median follow-up 5.0 years. Stratified as treatment-naive vs treatment-experienced; BCLC stage, tumor burden, performance status, and Child-Pugh class all captured at patient level.
EBRT delivered per each contributing series; the pooling filter was prespecified technical standards for HCC. Ablative dose was independently associated with reduced risk of death, but specific dose/fractionation schedules and the ablative-dose threshold are not reported in the source abstract.
Median OS 6.8 years for BCLC-0 and 4.6 years for BCLC-A; among treatment-naive pts not reached for BCLC-0 and 5.4 years for BCLC-A. On multivariable modeling, advanced BCLC stage, higher tumor burden, worse performance status, and Child-Pugh B/C raised mortality risk; ablative dose and more recent treatment year lowered it.
| Cohort | BCLC-0 | BCLC-A |
|---|---|---|
| All pts | 6.8 yrs (95% CI 5.7-8.7) | 4.6 yrs (95% CI 4.1-5.1) |
| Treatment-naive | NR (95% CI 8.6-NR) | 5.4 yrs (95% CI 4.5-6.7) |
The authors position these OS figures as comparable with resection, thermal ablation, and other ablative locoregional therapies. That comparison is across literatures, not within a trial, so the usual selection differences (lesion location, vascular proximity, comorbidity burden) between an EBRT-referred and a resection-eligible population remain unadjusted.
No comparator arm: the resection/ablation equivalence claim is a cross-study inference. IPD came only from authors who responded, and the technical-standard filter selects for expert centers, both biasing toward better outcomes. Year-of-treatment effect confounds technique era with staging and systemic-therapy improvements.
The practical argument here is algorithmic placement: BCLC has historically routed early HCC to resection, ablation, or transplant with EBRT absent, and this is the largest patient-level dataset assembled to contest that omission. The treatment-naive BCLC-0 result matters most, since it isolates first-line EBRT from salvage-after-ablation-failure use.
Large multinational prospective-collected IPD across many sites with stage-stratified analyses, but non-randomised and no head-to-head comparator; supports EBRT's guideline-listed role rather than establishing it.
In BCLC-0 or A HCC where ablation or resection is unattractive on lesion location or comorbidity, this supports offering ablative-dose EBRT as a first-line locoregional option rather than a salvage one; it does not speak to BCLC-B/C or Child-Pugh B-C pts, where OS was worse.
- Randomised EBRT vs thermal ablation in early HCC recruiting Stereotactic Radiosurgery Versus Radiofrequency Ablation for Primary Liver Cancer Phase 2n=130 · primary completion 2025-01 · randomised SBRT vs RFA, inoperable primary liver caactive Stereotactic Body Radiotherapy Versus Radiofrequency Ablation for Unresectable, Small (≤ 3 cm) HCC Phase NAn=178 · primary completion 2026-12 · randomised SBRT vs RFA in unresectable ≤3 cm HCCn=218 · primary completion 2032-04 · SABR vs percutaneous ablation, BCLC 0/A, 2y FFLP
- Ablative dose threshold defining the OS benefit
- Generalizability beyond expert EBRT centers