Real-world evidence
Focal Ablation vs IMRT Toxicity (SEER-Medicare)
ForLocalized prostate cancer, fee-for-service Medicare, mean age ~73
TL;DRGI toxicity favored focal therapy at 24mo (11.0% vs 21.5%, OR 0.45) but GU toxicity favored IMRT (41.7% vs 29.3%, OR 1.69).
The GI advantage rests on diagnosis claims alone: procedure-code-only GI events were too few to report and not significantly different, while the GU excess with FT was concrete (incontinence therapy 17.4% vs 7.5%). For an RT reader counseling an older man weighing ablation, that asymmetry is the point.
In an older man with localized prostate cancer choosing between focal ablation and IMRT, this supports counseling that the tradeoff runs GU-for-GI rather than uniformly lower toxicity with ablation; it does not extend to SBRT or proton patients, who were excluded.
The IMRT comparator is a 2010-2017, ≥20-fraction cohort with SBRT, protons and rectal hydrogel excluded, so the GI toxicity attributed to radiation predates spacer-era rectal sparing. That caps how much of this GI gap should carry into a current consent conversation, while the GU result (incontinence therapy 17.4% vs 7.5% favoring IMRT) transfers intact.
For ablation, the toxicity cost is concrete and periurethral: incontinence therapy 17.4% vs 7.5% and erectile dysfunction 18.2% vs 13.1%, both P<.01. The offsetting GI advantage collapsed in the procedure-only analysis, so the low-morbidity premise for cryotherapy and laser ablation in older men is weaker than the headline suggests.
10 details 5 trials watching
Retrospective SEER-Medicare claims analysis of localized prostate cancer diagnosed 2010-2017. 797 focal therapy patients Mahalanobis matched 2:1 to 1,594 IMRT patients on demographics, Medicaid eligibility, comorbidity, flu vaccination, primary care access, year, cancer characteristics and ADT. Logistic regression at 6, 12 and 24 months.
Fee-for-service Medicare beneficiaries with localized PCa as first and only cancer, continuously enrolled parts A and B from 12 months pre-diagnosis through 24 months post-treatment. New York, Idaho and Massachusetts registries excluded for missing AJCC staging. Patients who died within 24 months of treatment were excluded.
IMRT defined as external beam with no surgery plus ≥20 IMRT fractions and an IMRT planning code; a gap of ≥30 days between radiation dates counted as a separate course. SBRT and proton patients were excluded, as were patients with rectal hydrogel spacer, so the IMRT arm is conventional fractionation without a rectal spacer.
Presence of claims indicative of a GI or GU complication within 6, 12 and 24 months of treatment, assessed both as combined diagnosis and procedure codes and as procedure codes only. No patient-reported outcomes and no graded toxicity scale.
Direction reversed by organ system: GI favored focal therapy from 12 months onward, GU favored IMRT at every window measured. The 0-6 month GI comparison was null (OR 1.06, P=.81).
| Toxicity / window | FT | IMRT | OR (95% CI) |
|---|---|---|---|
| GI 0-6 mo | 3.6% | 3.5% | 1.06 (0.67-1.67), P=.81 |
| GI 0-12 mo | 6.2% | 9.5% | 0.63 (0.45-0.88) |
| GI 0-24 mo | 11.0% | 21.5% | 0.45 (0.35-0.58) |
| GU 0-12 mo | 34.6% | 15.8% | 2.69 (2.21-3.28) |
| GU 0-24 mo | 41.7% | 29.3% | 1.69 (1.42-2.01) |
GU excess with focal therapy was driven by incontinence therapy (17.4% vs 7.5%) and erectile dysfunction (18.2% vs 13.1%), both P<.01. GI events with IMRT were predominantly rectal bleeding and colitis; the authors note related procedures were rare and not significantly different.
Focal therapy patients were disproportionately rural (6.4% vs 1.9%) and lower-income (51.5% vs 38.7% in the lowest two quintiles) before matching, so claim-generating behavior may differ by arm independent of toxicity. Baseline continence and erectile function were unmeasured, which matters most for the two endpoints driving the GU result.
The GI result is fragile in a specific way the abstract does not foreground: it collapses to one diagnosis subcategory and disappears in the procedure-only analysis. The GU result is the more robust half, and it runs against the premise that ablation is the lower-toxicity option.
Claims-based retrospective matching, not randomised; toxicity defined by diagnosis codes, and the GI difference vanished when restricted to procedure codes. No PROs, no baseline function.
- Does the tradeoff hold vs SBRT or spacer-era IMRT? n=184 · primary completion 2027-06 · IRE vs prostatectomy or RT, side-effect endpointn=356 · primary completion 2029-08 · focal therapy vs usual care RCT, ISUP 2/3
- Do patient-reported outcomes track the claims-based GU signal? n=300 · primary completion 2030-12 · prospective validated urinary/sexual PROs after HIFUn=200 · primary completion 2032-03 · questionnaire outcomes across HIFU, cryo, laser, IRE
- Do HIFU and RFA carry the same GU profile as cryo/laser? n=354 · primary completion 2028-12 · HIFU hemi-ablation, continence + toxicity endpoints
📚 Sources · 📄 1 paper
Abstract
PSMA PET Natural History Study in PSMA-Positive BCR
ForBiochemically recurrent prostate ca, post-definitive + salvage RT, PSA ≥ 0.5
TL;DRBaseline data on first 130 pts: most BCR men with PSADT >9-12mo still have PSMA PET findings once PSA exceeds 5.
Reported via UroToday →
The RT-relevant point is where the disease sits: prostate bed recurrence and nodal disease are the dominant baseline patterns, all in men who already had or declined salvage RT. If most slow-PSADT pts light up above PSA 5, PET positivity alone cannot gate metastasis-directed SBRT, and the trigger has to come from kinetics or serial change.
In post-salvage-RT BCR with PSADT over 9mo and a PSMA PET showing a few nodal or bed lesions, this supports serial imaging over reflex systemic therapy; it says nothing about pts with rapid PSADT or conventional-imaging metastases.
Nodal disease and prostate bed recurrence dominate the baseline patterns in men already past salvage RT, so this is the population MDT gets offered to. If most slow-PSADT pts are PET-positive above PSA 5, lesion count reflects scan timing more than biology, which weakens PET positivity as the gate for SBRT.
Only about a third of the cohort has started any therapy, and only 5 of the first ~150 progressed on conventional imaging at ~1.5yr. That is the counterweight to reflex mCSPC-style doublet therapy triggered by PSMA PET findings in men whose PSA kinetics are slow.
11 details
Prospective observational natural history cohort at the NCI, presented at GU-ASCO 2026. Baseline data on the first 130 pts; the cohort is ongoing at a median follow-up of about 2 years with interim outcome data pending.
Men with biochemical recurrence after definitive therapy, all of whom had already received salvage radiation or declined it. PSA ≥ 0.5 required for a baseline PET. Deliberately framed as PSMA-positive BCR, a state that would not have been detectable in the historical trials these pts map onto and that excluded them from metastatic trials.
The presented analysis is cross-sectional: PSMA PET findings at baseline against PSA doubling time, the field's working predictor of metastasis in BCR. Imaging cadence is protocolized at annual if the baseline PET is negative, every 6 months if anything is seen, including equivocal findings.
Among pts with slow kinetics (PSADT > 9mo and > 12mo), the majority still had PSMA PET findings once PSA was above 5: nodal disease, prostate bed recurrence, and small equivocal bone lesions. Only about a third have started any therapy. A companion poster found 5 of the first ~150 pts progressed on conventional imaging at roughly 1.5yr, and over 95% showed no abrupt PET change out of step with PSA.
The counts are reported conversationally in an interview ("about 130", "the first 150 or so", "that number's five"), with no stratum denominators and no CIs, so the PSADT-by-PET relationship cannot be quantified from this source. Allowing any therapy under 6 months, including SBRT and intermittent ADT, means the observed group is not an untreated comparator.
The claim being staked is that PSMA PET positivity in BCR is near-ubiquitous above PSA 5 and therefore weakly discriminating, so it should not by itself trigger treatment. What the cohort has not yet shown is whether PET burden or its change over time adds anything to PSA doubling time for predicting the outcomes that matter.
Baseline cross-sectional read of an ongoing single-institution cohort, median f/u ~2yr, no outcome analysis yet. Numbers reported conversationally, not tabulated.
- Does PET burden or its change add to PSA doubling time for predicting progression?
- Which PSMA-positive BCR pts can safely be observed off therapy?
- Are small equivocal bone lesions on PSMA PET true metastases?
📚 Sources · 📄 1 paper
Abstract
GÖTEBORG-1
ForScreen-detected very-low/low/intermediate-risk prostate cancer on active surveillance
TL;DR25yr PC-specific survival 94% on active surveillance, but failure-free survival fell to 68% at 22yr.
The RT-relevant number is durability of the cure window: 18 of 81 failures were PSA relapse after RP or RT, and failure-free survival kept falling to 68% at 22 yr with no plateau. Intermediate-risk 19-yr failure-free survival was 55%, which frames how long a deferred definitive-RT candidate stays salvageable.
In screen-detected very-low-risk disease, this supports counselling that deferring prostatectomy or radiotherapy carries roughly 1% PC death at 24 yr; it is weaker footing for intermediate-risk pts, where 19-yr failure-free survival was 55% and 24-yr PC-specific survival 85%.
Forty-four men came to RT after leaving surveillance, and 18 of 81 failures were PSA relapse after RP or RT, so a share of deferred pts arrive needing salvage rather than definitive intent. Intermediate-risk failure-free survival was 55% at 19 yr, which bounds how long deferral stays safe.
Forty-four of 81 failures were starting hormonal therapy, mostly for symptoms, meaning the commonest surveillance failure lands as ADT rather than a cancer death. PC-specific survival stayed 94% at 25 yr, so the trade is systemic therapy exposure, not mortality.
RP was the dominant exit from surveillance, 141 of 232 discontinuations. Gleason 7 carried failure HR 3.12 (1.59-6.13) and PSA density per doubling HR 1.78 (1.22-2.59), the two factors that should gate whether an AS candidate is counselled toward earlier resection.
11 details
Prospective observational cohort nested in the Göteborg-1 PSA screening trial. Of 1052 men diagnosed with screen-detected PC between 1995 and 2014, 494 (47%) had AS as primary strategy and 488 were analysed after excluding 6 with high-risk disease. Follow-up closed December 31, 2023; median follow-up among survivors 18.0 yr.
Very low risk 251 (51%), low risk 129 (26%), intermediate risk 108 (22%). Median age 66 yr (IQR 63-68), PSA 4.1 ng/ml, PSA density 0.12 ng/ml/cm3. Intermediate risk was T1-2, Gleason 7, PSA <20; high-risk disease (Gleason 8 or above) was excluded.
AS was defined as no treatment within 6 mo of diagnosis, with no predefined selection or follow-up protocol. PSA every 6-12 mo, repeat biopsy on clinical or PSA progression, early rebiopsy when the diagnostic core carried under 2 mm of cancer. Sextant biopsies until 2009, 10-12 cores thereafter.
RT was a discontinuation endpoint, not a protocol intervention: 44 men received radiotherapy as primary treatment after leaving AS versus 141 radical prostatectomy and 47 hormonal therapy. No dose, fractionation, or target volume is reported. Post-RT failure was defined by the nadir +2 ng/ml rule.
Kaplan-Meier treatment-free, failure-free, PC-specific and overall survival, measured from diagnosis. Failure was a composite: noncurative PSA relapse, starting hormonal treatment, metastasis, or PC death, whichever came first. Curves truncated at 22 yr for treatment- and failure-free survival for want of men at risk.
232 men discontinued AS, 81 met the failure definition, 14 died of PC. Risk of failure rose with Gleason 7 (HR 3.12), PSA density per doubling (HR 1.78), and T2a-c stage (HR 1.89); age and PSA alone were not associated.
| Endpoint | 15 yr | 20 yr | 22-25 yr |
|---|---|---|---|
| PC-specific survival | 97% (95-99) | 95% (93-98) | 94% (91-98) at 25 yr |
| Overall survival | 63% (58-67) | 46% (41-51) | 32% (26-38) at 25 yr |
| Treatment-free survival | 48% (43-54) | 43% (37-50) | 38% (31-46) at 22 yr |
| Failure-free survival | 81% (77-85) | 74% (68-81) | 68% (60-78) at 22 yr |
| Endpoint | Very low risk | Low risk | Intermediate risk |
|---|---|---|---|
| Treatment-free survival, 19 yr | 55% (48-63) | 35% (26-47) | 30% (18-48) |
| Failure-free survival, 19 yr | 85% | 74% | 55% |
| PC-specific survival, 24 yr | 99% (97-100) | 92% (83-100) | 85% (75-95) |
| Overall survival, 24 yr | 38% (30-48) | 34% (26-45) | 22% (12-37) |
Treatment-free survival at 15 yr (48%) sits between the Toronto AS cohort (55% at 15 yr) and Canary PASS (49% at 10 yr). PC mortality is close to ProtecT (3.4%) and Toronto (5.7% at 15 yr), and well below PIVOT (11.4%) and SPCG-4, which enrolled clinically diagnosed rather than screen-detected men.
Sextant biopsy through 2009 and MRI in only 21 of 488 men mean baseline risk group is systematically understated, so some "very-low-risk" failures were likely misclassified intermediate-risk disease at entry. The 2005 Gleason revision shifts the same tumours upward today. The composite failure endpoint also pools an untreated low-value PSA relapse with PC death.
The two headline numbers point in opposite directions and both are real: cancer-specific survival of 94% at 25 yr says AS is safe, while failure-free survival of 68% at 22 yr with no plateau says the cure window closes for a substantial minority. The authors' framing is the useful one: there is no point at which monitoring can be stopped safely.
Prospective single-strategy cohort nested in a screening RCT, no randomised treatment comparator; extends known AS safety signal to 25 yr rather than contesting it.
- Does MRI-and-targeted-biopsy-era AS lower the long-term failure rate
- Is intermediate-risk AS safe beyond 19 yr
- Optimal surveillance intensity after 15 yr on AS
📚 Sources · 📄 1 paper
MROQC ADT Practice Patterns
ForIntact high-risk M0/N0-1 prostate ca planned for definitive RT
TL;DR67.0% of 553 high-risk pts got guideline-concordant ADT (≥18mo); ARPI use 23.2% among STAMPEDE-eligible post-publication.
The deviation is concentrated where the guideline is weakest-anchored: cN1 (OR 2.94) and GG4-5 (OR 6.23 / 9.45) drove ≥18mo recommendations, so the third of pts NOT getting guideline-concordant ADT are largely single-factor high-risk. Facility remained a predictor after case-mix adjustment (P<.0001), which points at practice culture, not patient selection.
For a man with single-factor high-risk localized disease (GG4-5 or PSA ≥20 alone) heading to definitive RT, this frames how much of the ≥18mo ADT recommendation is guideline versus local habit; it does not address post-prostatectomy salvage or M1 disease.
GC-ADT tracked the features that also define STAMPEDE M0 eligibility (GG4 OR 6.23, GG5 OR 9.45, cN1 OR 2.94), so the non-concordant third is enriched for single-factor high-risk disease. Facility stayed predictive after case-mix adjustment (P<.0001), making department habit, not patient selection, the target.
ARPI intensification reached only 23.2% of STAMPEDE M0-eligible pts after publication, up from 0%. With 27.9% of this high-risk RT population eligible, the referral and co-management pathway for adding an ARPI to definitive RT plus ADT is the bottleneck, not the evidence.
9 details
Prospective observational analysis within the Michigan Radiation Oncology Quality Consortium (MROQC), a statewide quality collaborative. 26 centers, accrual June 2020 to November 2024, N=553. Intended ADT duration and ARPI use were collected prospectively at the treatment decision, not abstracted retrospectively.
Intact (non-postoperative) high-risk M0/N0-1 prostate cancer planned for definitive radiotherapy. Risk features: cT3/4 13.3%, cN1 19.9%, GG 4-5 75.0%, PSA ≥20 ng/mL 40.0%.
Primary outcome was intended guideline-concordant ADT (GC-ADT, ≥18 months) per the 2022 AUA/ASTRO recommendation of 18-36 months. Secondary analyses covered multivariable predictors of GC-ADT, ARPI adoption before versus after STAMPEDE M0 publication, and facility-level variability via a mixed-effects model with treatment site as random intercept.
91.3% were recommended ADT and 67.0% were guideline-concordant. Among the 27.9% meeting STAMPEDE M0 eligibility, ARPI recommendation went from 0% pre-publication to 23.2% after. Site-level variability remained significant on multivariable analysis (P<.0001).
| Factor | OR (95% CI) |
|---|---|
| cN1 | 2.94 (1.44 to 5.99) |
| GG4 | 6.23 (2.85 to 13.62) |
| GG5 | 9.45 (4.46 to 20.06) |
| PSA ≥40 | 3.64 (1.22 to 10.87) |
The 2022 AUA/ASTRO guideline sets 18-36 months, and STAMPEDE M0 supports ARPI intensification for ≥2 of cT3/T4, GG 4-5, PSA ≥40, or cN1. Both benchmarks are met by a minority here, echoing the long-standing gap between the long-course ADT durations tested in EORTC 22863 and RTOG 9202 era trials and what is actually intended in practice.
Intended duration is a proxy for delivered duration, so the true concordance rate could fall further with early discontinuation. STAMPEDE M0 eligibility was applied to a cohort accrued partly before that trial reported, so the 23.2% post-publication figure reflects an adoption curve still in motion rather than a steady state.
The finding that facility explains variance after adjusting for cN1, grade group, and PSA is the load-bearing result: with case mix accounted for, where a man is treated still moves how long he is recommended ADT. That is a quality-improvement target rather than an evidence gap, and it is the kind of signal a consortium is uniquely built to detect and act on.
Prospective practice-pattern survey of intended treatment, no efficacy endpoint. Documents a care-delivery gap rather than testing whether the guideline duration is right.
- Does intended ADT duration match delivered duration?
- Which facility-level factors drive the residual variability?
- Optimal ADT duration for single-factor high-risk disease
📚 Sources · 📄 1 paper
Abstract
COMPPARE
ForDe novo localized prostate cancer, excluding very high risk and metastatic
5.7% vs 6%
P=0.28, hypothesized 7% vs 15%
TL;DRProton vs IMRT: no difference in bowel urgency (5.7% vs 6%), ≥G2 GI toxicity (5.2% vs 5.6%), or 3yr disease control.
The spacer table is the actionable finding, not the modality comparison: 2yr GI G2+ fell to 4.4% (IMRT) and 4.7% (proton) with a spacer vs 7.2% and 8.7% without, P=0.009. Rectal separation, available at any IMRT center, delivered what particle therapy did not.
In de novo localized prostate cancer outside very high risk, this argues the rectal-sparing decision sits with spacer placement rather than referral to a proton center; it says nothing about late GU endpoints or very high risk disease.
The spacer stratum, not the modality arm, is where the toxicity separated: 2yr GI G2+ 4.4% (IMRT, spacer) and 4.7% (proton, spacer) vs 7.2% and 8.7% without, P=0.009. That moves the rectal-sparing decision toward spacer placement at your own center rather than proton referral.
| Outcome | Hypothesized IMRT | Hypothesized PT | Actual IMRT | Actual PT | P-value |
|---|---|---|---|---|---|
| Bowel urgency | 15% | 7% | 6% | 5.7% | 0.28 |
| Bowel frequency | 10% | 4% | 4% | 3.5% | 0.43 |
| GI toxicity CTCAEv5 ≥2 | 29% | 20% | 5.6% | 5.2% | 0.60 |
| Freedom from progression 3yr | 89% | 91% | 97.9% | 98.0% | 0.90 |
+2 more figures
| Group | 2yr cumulative CTCAE v5 GI G2+ | P |
|---|---|---|
| IMRT, no spacer | 7.2% (5.0%, 9.9%) | 0.009 |
| Proton, no spacer | 8.7% (5.0%, 14%) | |
| IMRT, spacer | 4.4% (2.8%, 6.4%) | |
| Proton, spacer | 4.7% (3.6%, 6.0%) |
8 details 4 trials watching
Prospective nonrandomised comparative-effectiveness cohort study funded by PCORI, comparing proton therapy and IMRT across 51 centers. Accrual 2524 pts from July 2018 to October 2022, allocated to a proton cohort (1500) and a photon cohort (1000).
All de novo prostate cancer except very high risk and metastatic. The exclusion is the boundary that matters: the pts in whom elective nodal coverage and integral dose arguments are strongest were never enrolled.
Primary: patient-reported bowel urgency and bowel frequency (EPIC) and CTCAE v5 ≥G2 GI toxicity, each powered at 90%. Freedom from disease progression at 3 years (PSA) was exploratory, not powered.
Every prespecified comparison was null. The more telling result is that observed rates undershot the design assumptions in both arms: ≥G2 GI toxicity 5.6% IMRT and 5.2% proton against 29% and 20% hypothesized.
Rectal spacer use separated the toxicity curves where modality did not. 2yr cumulative ≥G2 GI toxicity was 4.4% (2.8%, 6.4%) IMRT with spacer and 4.7% (3.6%, 6.0%) proton with spacer, vs 7.2% (5.0%, 9.9%) and 8.7% (5.0%, 14%) without, P=0.009 by Gray's test.
The ≥G2 GI rates here are far below the toxicity burden that motivated the proton hypothesis, and align with the modern IMRT plus spacer experience rather than the older photon series the 29% assumption was drawn from.
Cohort allocation, not randomisation, so the arms differ by referral pattern, geography, and insurance in ways baseline adjustment cannot fully absorb. The unequal cohort sizes (1500 vs 1000) reflect enrollment at proton-capable centers, not a design ratio.
A null comparative-effectiveness result in a low-event setting is weak evidence of equivalence and strong evidence that the toxicity target moved. The question the field now needs answered is late toxicity and second malignancy, which 3 years cannot address.
Nonrandomised prospective cohort comparison; residual confounding unaddressable. Null on every prespecified endpoint, but 3yr follow-up cannot capture the late toxicity protons are argued to prevent.
- Late GI and GU toxicity beyond 3 years n=303 · primary completion 2026-12 · proton vs IMRT hypofx registry, f/u to 2026n=400 · primary completion 2027-03 · randomised proton vs photon, late GI primary EPrecruiting Reduction of Gastrointestinal Toxicity in Prostate Cancer by Proton Spot Placement Phase NAn=500 · primary completion 2030-01 · proton LET vs rectal/bladder toxicity, n=500
- Second malignancy risk from integral dose
- Whether protons add anything once a spacer is placed n=50 · primary completion 2025-09 · 2-arm spacer trial in pts planned for proton
📚 Sources · 🐦 1 tweet
#COMPPARE early results: in localized #ProstateCancer, #proton therapy vs #IMRT showed no sig difference in pt-reported bowel urgency/frequency, ≥G2 GI toxicity, or 3-year biochemical control. Longer follow-up needed for late toxicity/long term outcomes #ASCO2026 pic.twitter.com/yli4l8nEOY
— QianJanieQin (@QianJanieQin) May 31, 2026
OCEANUS
ForAdvanced or refractory NSCLC receiving both RT and an ICI
20.3 vs 16.0 mo
aHR 0.68, 95% CI 0.47-0.99, P=.045 (sequential vs concurrent)
TL;DRSequential iRT beat concurrent for OS in newly diagnosed advanced NSCLC (20.3 vs 16.0 mo, aHR 0.68, P=.045); territory-wide cohort.
For an RT reader the actionable variable is timing, and the only signal here favors giving RT sequentially rather than concurrently with ICI (20.3 vs 16.0 mo, aHR 0.68). But the source reports no dose, fractionation, target volume or pneumonitis rate, so the parameter that would let you transfer this to a plan is absent.
In newly diagnosed advanced NSCLC already going on an ICI who also need thoracic or palliative RT, this weakly supports separating RT from the ICI start rather than overlapping them; it says nothing about stage III unresectable chemoRT-plus-durvalumab, where the concurrent-then-consolidation standard is randomized.
The only actionable variable is timing: sequential rather than concurrent RT with ICI carried longer OS (20.3 vs 16.0 mo, aHR 0.68). Dose, fractionation, target volume and pneumonitis rates are absent from the source, so the parameters that would let you build a plan around this are missing.
Chemotherapy alongside iRT was associated with longer OS in newly diagnosed advanced disease but not in refractory disease, and ICI maintenance after RT in refractory pts was not significant (11.2 vs 6.7 mo, P=.20). This argues against dropping the chemo backbone in the newly diagnosed setting when RT is added.
13 details 3 trials watching
Territory-wide retrospective cohort (OCEANUS) using the Hong Kong Hospital Authority CDARS, covering more than 90% of the population. Propensity score overlap weighting was the primary method with IPTW for sensitivity; analysis ran December 2024 to April 2025. Landmark analysis was applied, and refractory pts had to survive at least 90 days.
NSCLC diagnosed January 1, 2010 to December 31, 2021 who subsequently received iRT for advanced or refractory disease. Of 3522 pts who received ICIs, 335 received RT: 155 newly diagnosed advanced and 180 refractory. 247 (73.7%) male, median age 64 (range 34-90).
The exposure is RT timing relative to ICI, sequential vs concurrent, in newly diagnosed disease, and RT with vs without ICI maintenance in refractory disease. Dose, fractionation, modality, target volume and irradiated site are not reported in the source, which is the gap that limits transfer to a specific plan.
Primary: real-world OS after landmark, estimated with weighted Kaplan-Meier and Cox models. Where proportional hazards were violated per Schoenfeld residuals, effects were summarized with restricted mean survival time.
Sequential iRT carried longer OS than concurrent in newly diagnosed advanced disease, aHR 0.68 (0.47-0.99), P=.045. In refractory disease the ICI-maintenance difference was not significant (P=.20), and added chemotherapy showed no significant OS association there.
PACIFIC established consolidation durvalumab after concurrent chemoRT in stage III unresectable disease, and PEMBRO-RT and MDACC randomized data tested RT added to pembrolizumab in metastatic disease, but none of these randomize sequential against concurrent iRT in advanced NSCLC. That question has no randomized answer, which is why a 155-pt weighted cohort is currently among the larger reads on it.
Timing was clinician-assigned, so pts pushed to concurrent RT plausibly had more urgent, symptomatic or bulky disease, an indication bias that overlap weighting on recorded covariates cannot remove. The 2010-2021 window also mixes ICI eras, agents and lines, and the source reports no toxicity, so the pneumonitis risk that motivates avoiding concurrency is unmeasured here.
The result argues that separating RT from ICI administration does not cost survival and may favor it, which is the opposite of the abscopal-synergy rationale often used to justify concurrency. It does not establish causality, define an interval, or identify which pts the timing matters for.
Retrospective propensity-weighted registry cohort, 155 pts in the primary comparison, P=.045 with CI touching 1.0. Authors themselves call it hypothesis generating.
- Optimal interval between RT and ICI administration active Concurrent or Sequential Immunotherapy and Radiation Therapy in Patients With Metastatic Lung Cancer Phase 1n=78 · primary completion 2026-12 · randomises seq vs concurrent SBRT + nivo/ipi in stage IV
- Whether concurrent iRT increases pneumonitis in advanced NSCLC n=150 · primary completion 2027-02 · biomarker cohort tracking pneumonitis after CRT then ICI
- Which pts, if any, benefit from concurrent rather than sequential timing active Concurrent or Sequential Immunotherapy and Radiation Therapy in Patients With Metastatic Lung Cancer Phase 1n=78 · primary completion 2026-12 · same SBRT dose levels in each timing arm, stage IV NSCLC
📚 Sources · 📄 1 paper
Abstract
DBCG IMN2 NCT06549920
ForNode-positive breast cancer, macrometastatic, adjuvant taxane/trastuzumab/AI era
HR 0.85
95% CI 0.76-0.94, p=0.0016; 15y OS 65.0% vs 60.8%
TL;DRIMNI cut 15y mortality: OS 65.0% vs 60.8%, adjusted HR 0.85 (0.76-0.94), p=0.0016, in 4541 node-positive pts.
The 1-3 node group (n=3100, HR 0.85, 0.73-0.97) is the whole point: that is exactly where guidelines allow IMNI omission, and no measured factor identified a safe-omission subgroup. Right-sided IMN CTV V90% coverage was 94.6% with 25% under 64.8%, so a modern gated VMAT plan should exceed the dose separation that produced this 4.2% 15y OS gain.
In macrometastatic node-positive breast cancer with 1-3 involved axillary nodes going to locoregional RT, this supports including the internal mammary chain rather than omitting it; it does not speak to pts treated with neoadjuvant systemic therapy, who were excluded.
The 1-3 node subgroup (n=3100, HR 0.85, 0.73-0.97) removes the usual reason to skip the IMN chain, and no measured factor found a safe-omission group. Right-sided IMN CTV V90% was 94.6% with a quarter under 64.8%, so gated VMAT should beat the dose separation that produced this 4.2% 15y OS gain.
Benefit persisted on a modern backbone: 96.2% of chemo pts got a taxane, 13.5% trastuzumab, aromatase inhibitors postmenopausal, and the absolute 15y OS gain of 4.2% matched IMN1's 4.7% from the pre-taxane era. Effective systemic therapy did not absorb the regional RT effect, so this argues against dropping locoregional RT as drugs improve.
12 details
Nationwide population-based prospective cohort across six Danish RT centres, 2007-14, allocating IMNI by tumour laterality (right yes, left no) under national guideline. N=4541 of 5206 assessed. Median follow-up 13.7 years for OS, 13.2 for distant metastasis; analysis was intention-to-treat by side.
Macrometastatic node-positive breast cancer receiving locoregional RT; median age 59; 68.3% had 1-3 positive nodes. Excluded: prior malignancy, bilateral disease, neoadjuvant systemic therapy, recurrence before RT, non-standard RT. Axillary surgery was always axillary dissection.
Chemotherapy was three cycles EC (epirubicin 900 mg/m2, cyclophosphamide 600 mg/m2) then three cycles docetaxel 100 mg/m2; 96.2% of chemo pts received a taxane. Tamoxifen premenopausal, aromatase inhibitor postmenopausal; trastuzumab concurrent with chemo and RT in HER2+ (13.5% overall).
48 Gy/24 Fx before Jan 2009 (26.2%), 50 Gy/25 Fx after (73.2%), 3D conformal wide tangents in free-breathing. IMN target was intercostal space 1-4; all pts had axilla level II-III plus interpectoral and level IV, with level I added for ≥6 positive nodes or <10 nodes removed. QA showed IMN CTV V90% 94.6% right vs 20.4% left.
Primary: overall survival. Secondary: breast cancer mortality and distant metastasis, both with non-breast-cancer death as a competing event. Cox models adjusted for age, menopausal status, histology, tumour size, and nodal count, stratified by IHC subtype and grade.
The OS point estimate sits on top of the EBCTCG regional-node meta-analysis rate ratio 0.90 (0.84-0.96) and of KROG 08-06's HR 0.87 (0.57-1.31), the only other 3D-based IMNI study, which was underpowered at n=735 and read as negative. It also reproduces DBCG IMN1's absolute OS gain of 4.7%, arguing the taxane/trastuzumab/AI era did not absorb the benefit.
Contamination runs both ways: 10.1% of left-sided pts (n=238) got IMNI and a quarter of right-sided pts had under 64.8% IMN coverage, so the observed gain likely understates a fully delivered one. Cardiac and lung toxicity were captured only as death, with no smoking, comorbidity, or cardiac-event data, and the era predates PET-CT staging and respiratory gating.
The ER-/HER2+ signal (HR 1.49, 0.98-2.25, interaction p=0.021) echoes Kyndi's DBCG 82b&c finding but conflicts with NSABP B-51, and the analysis was explorative without multiplicity correction, so it should not gate treatment. The medial/central plus ≥4 node cell (HR 0.98, 0.79-1.21) is the one group where benefit looks absent, matching IMN1's 0.91 (0.73-1.15).
| Endpoint | IMNI | No IMNI | Adjusted HR (95% CI), p |
|---|---|---|---|
| OS at 15y | 65.0% | 60.8% | 0.85 (0.76-0.94), p=0.0016 |
| BC mortality at 15y | 21.4% | 23.6% | 0.84 (0.74-0.95), p=0.0077 |
| Distant mets at 15y | 25.1% | 26.9% | 0.87 (0.78-0.98), p=0.026 |
CONSORT flow
Prospective nationwide cohort, prespecified primary endpoint, 13.7y follow-up; contradicts guidelines withholding IMNI at 1-3 nodes. Non-randomised laterality allocation keeps it below practice-changing.
- Effect of IMNI alongside immunotherapy and antibody-drug conjugates
- Is ER-/HER2+ a genuine predictive subtype for IMNI harm
- Safe RT omission in cN+ pts with pCR after neoadjuvant therapy
📚 Sources · 📄 1 paper
Tumour bed boost after BCS+WBRT (Dutch cohort)
ForPost-BCS invasive breast cancer receiving WBRT, boost decision pending
TL;DR10yr IBTR 1.2% with 0-2 risk factors regardless of boost, supporting boost omission in the modern systemic era.
The decision this moves is boost omission, and the number that moves it is 10yr IBTR 1.2% in the 0-2 risk-factor group whether or not a boost was given, on 15,085 vs 13,845 pts. Note the ≥3 group ran higher WITH boost (3.3% vs 2.7%), which is allocation bias, not boost harm. Boost dose and fractionation are not in the source.
In a post-BCS patient over 40 with grade 1-2, hormone-receptor-positive disease receiving guideline-concordant systemic therapy, this supports omitting the tumour bed boost; it does not resolve the boost question for pts carrying three or more risk factors.
The omission decision rests on 10yr IBTR of 1.2% in the 0-2 risk-factor group with and without boost (15,085 vs 13,845 pts). The ≥3 stratum ran higher WITH boost (3.3% vs 2.7%), a signature of risk-based allocation rather than boost harm. Boost dose and fractionation are absent from the source.
| Risk factors | N no boost | N boost | 5yr no boost | 5yr boost | 10yr no boost | 10yr boost |
|---|---|---|---|---|---|---|
| 0-2 | 15,085 | 13,845 | 0.6% | 0.7% | 1.2% | 1.2% |
| ≥ 3 | 149 | 733 | 1.3% | 2.9% | 2.7% | 3.3% |
| Uncertain | 592 | 944 | 0.8% | 3.3% | 1.4% | 3.6% |
+2 more figures
9 details
Population-based Dutch cohort from the Netherlands Cancer Registry linked to pathology, on behalf of the DBRT group. Treatment years 2012-2016, follow-up to 10 years. Observational, no randomisation and no adjusted comparison reported in source.
Breast-conserving treatment with or without an RT boost, N=31,348 across the three risk strata. Stratification is by a count of five risk factors: age ≤40, grade 3, triple-negative, guideline-indicated systemic therapy not adequately given, and no pCR after neoadjuvant chemo in TNBC or HER2+.
Whole-breast RT with or without a tumour bed boost. Boost dose, fractionation, technique (photon vs electron vs SIB) and the WBRT schedule are not reported in the source slides, which limits transfer to a specific departmental protocol.
Primary: ipsilateral breast tumour recurrence (IBTR), histologically confirmed, identified by an algorithm over pathology report codes and free text. Reported as cumulative incidence at 5 and 10 years by risk-factor count. Benchmarked against the Assisi thresholds: omission acceptable at <3% 10yr IBTR with boost, <6% without.
IBTR was low in every stratum. The only cell crossing an Assisi threshold was ≥3 risk factors treated with a boost at 10 years, and even there the no-boost value in the same stratum was lower.
EORTC 22881-10882 established that a boost roughly halves IBTR, and that trial's control-arm event rates were an order of magnitude above these. IMPORT HIGH and the 2024 Assisi think tank both moved the field toward de-escalating or restricting the boost; this cohort supplies the contemporary absolute rates those recommendations assumed but could not show.
Boost was allocated by guideline-based risk, so the boost groups are adversely selected and the raw contrast understates any boost effect; the higher rate in the ≥3 boost group is the visible signature of that confounding. The ≥3 no-boost cell holds only 149 pts, and the 'uncertain' stratum (592 / 944) shows a boost-no-boost gap wide enough to suggest unmeasured risk is driving allocation there too.
The finding is about absolute rather than relative benefit: a preserved 50% relative reduction applied to a 1.2% 10-year event rate is not worth five extra fractions and a fibrosis penalty. What the cohort cannot say is whether the boost is the reason those low-risk rates are low, since roughly half the low-risk group received one.
Registry cohort, no randomisation and no adjusted effect estimate; boost allocation confounded by risk. Supports the direction already set by IMPORT HIGH and Assisi thresholds.
- Which ≥3 risk-factor subgroups actually benefit from a boost
- Whether boost omission holds under randomised testing in low-risk pts
- Boost dose and technique used across this cohort
📚 Sources · 🐦 1 tweet
Day TWO of #ESTRO26 Coverage by OncoAlert 🚨
— OncoAlert (@OncoAlert) May 16, 2026
Is a boost to the tumour bed still indicated after breast-conserving surgery and whole-breast radiotherapy in the era of modern systemic therapy? Presented by Femke Froklage 🇳🇱 #RadOnc ☢️
We aimed to identify a subgroup of breast… pic.twitter.com/RqK5r9XPqW
OligoCare
ForOligometastatic solid tumors treated with SABR, mixed primaries and lesion sites
TL;DRReal-world SABR local failure 5.0% at 1yr, 11.4% at 3yr across 2447 pts / 3533 lesions; CRC worst at 19.6%.
The actionable RT signal is minimum PTV dose, called the single most critical technical factor, and the de novo vs repeat OMD gap the authors attribute to higher delivered dose. CRC failed most (19.6% at 3yr) despite the highest median dose per fraction, which argues for escalation or combination rather than coverage alone. No dose thresholds are reported in source.
For a prostate or NSCLC oligomet being planned for SABR, this real-world cohort supports expecting durable in-field control (8.1% and 9.8% failure at 3yr); it does not support the same expectation for a colorectal met, where 3yr failure reached 19.6%.
Minimum PTV dose is named the most critical technical factor, so coverage of the low-dose region, not the prescription isodose, is where the planning attention goes. CRC failed worst (19.6% at 3yr) despite the highest median dose per fraction, so escalation alone may not close that gap. No dose thresholds reported in source.
SABR delivers 88.6% in-field control at 3yr in routine practice, so local failure is not the dominant driver of progression in most oligometastatic primaries. The exception is colorectal, at 19.6% failure by 3yr, where the authors suggest combination systemic approaches alongside local therapy rather than dose escalation alone.
| Primary | Total | 1 year | 3 years |
|---|---|---|---|
| Colorectal | 518 | 9.3% | 19.6% |
| Breast | 378 | 4.1% | 11.3% |
| NSCLC | 530 | 6.0% | 9.8% |
| Prostate | 1021 | 2.7% | 8.1% |
+2 more figures
10 details 4 trials watching
Prospective EORTC OligoCare registry cohort, interim analysis. 57 institutions, enrolment July 2019 to July 2025. No randomisation and no comparator arm; technique and dose were chosen by the treating institution.
2447 eligible pts with 3533 lesions. Median age 69 (range 28-94), 69% male. Primaries reported for the local-control breakdown were prostate (1021), NSCLC (530), colorectal (518) and breast (378).
SABR to oligometastatic lesions across bone (869 non-vertebral, 515 spine), lung (807), non-regional nodes (558), liver (306), brain (231) and other (247) sites. Minimum PTV dose was the technical factor most associated with outcome; specific dose and fractionation schedules are not reported in source.
Local in-field progression, reported as cumulative incidence with 99% CI, at 1 and 3 years. Median follow-up 31 months, minimum 6 months.
Overall local in-field progression 5.0% at 1yr and 11.4% at 3yr, ie 88.6% local control at 3yr. By primary, colorectal was the outlier and prostate the best.
Randomised oligometastatic SABR trials (SABR-COMET, STOMP, ORIOLE) were built on much smaller, more selected cohorts and reported survival or progression endpoints rather than lesion-level in-field control at this scale. This registry does not test the SABR question those trials asked; it reports what in-field control looks like once SABR is delivered in routine multi-institutional practice.
Dose and fractionation were institution-chosen, so the minimum-PTV-dose association is confounded by target site, prior irradiation and case selection. No PTV dose threshold, no per-primary dose data and no toxicity are reported in source, so the technical conclusion cannot be translated into a planning constraint.
The CRC finding is the one that changes a plan: worst local control despite the highest median dose per fraction points at intrinsic radioresistance rather than underdosing, and the authors call for escalation or combination strategies. The de novo versus repeat OMD gap is reported as a dose effect, which is plausible but is exactly the kind of comparison a registry cannot separate from the reasons a lesion is being re-treated.
Prospective multi-site registry, no randomised comparator, institution-chosen technique. Large real-world cohort supports existing SABR practice in OMD rather than testing it.
- Minimum PTV dose threshold that predicts local control
- Combination or dose-escalation strategies for colorectal oligomets recruiting Fruquintinib Combined With Sintilimab ± Radiotherapy for Third-line Treatment of Colorectal Cancer With Liver Metastases Phase 2n=62 · primary completion 2026-10 · SBRT+LDRT with sintilimab/fruquintinib, MSS CRC liverrecruiting Low and Intermediate Risk OliGometastatic ColoREctal CancEr PatieNts Treated with Stereotactic ABlative Radiotherapy Phase NAn=204 · primary completion 2031-04 · randomised SABR + chemo in 1-3 CRC oligomets
- Whether repeat OMD failure reflects dose or disease biology active Bony M - Stereotactic Ablative Radiotherapy (SABR) of Bony Metastases in Patients With Oligometastatic Disease Phase NAn=67 · primary completion 2023-01 · SABR in de novo vs recurrent OMD bone lesionsn=397 · primary completion 2028-06 · MR-guided adaptive SBRT, tumor control by site
📚 Sources · 🐦 1 tweet
📣 #ESTRO26 - @UmbertoRicardo e2irradiate @EORTC prospective OLIGOCARE registry of SABR for oligomets. ~2500 patients, ~3500 mets.
— Shankar Siva (@_ShankarSiva) May 17, 2026
➡️ local failure 5% at 1 year and 11% at 3 years
➡️ Colorectal cancer has higher risk of progression
➡️ minimum PTV dose correlated with outcome… pic.twitter.com/cx4zERqHhK