PEACE V-STORM NCT03569241
ForPelvic nodal oligorecurrence (≤5 nodes) on PET after radical local therapy
63% vs 76% at 4yr
HR 0·62 (80% CI 0·44-0·86), p=0·063; α set at 0·20
TL;DR4yr MFS 76% vs 63% with elective pelvic nodal RT over MDT, HR 0·62 (80% CI 0·44-0·86), p=0·063.
The clean radiation read is locoregional control, not MFS: 85% vs 62% at 4 years, HR 0·45 (80% CI 0·31-0·65), and pelvic nodal relapse fell from 29% to 8%. Toxicity did not follow the field: grade 2+ GI 9% vs 7%. Prostate bed inclusion, not pelvic volume, drove GI events (OR 4·6 [95% CI 1·5-15·8]).
In a man with ≤5 PET-positive pelvic nodes after prostatectomy or definitive RT, this supports treating the whole pelvis with a nodal boost rather than nodes alone when 6 months of ADT is being given; it says nothing about node-negative biochemical relapse or extrapelvic disease.
Field size is the whole question and locoregional control is the clean answer: 85% vs 62% at 4 years, HR 0·45, with pelvic nodal relapse 8% vs 29%. The deliverable is 45 Gy/25 fx whole pelvis to L4-L5 with a 65 Gy SIB, and the added pelvic volume cost nothing in GI toxicity (9% vs 7%); the prostate bed did (OR 4·6).
Both arms received an identical 6 months of ADT, so nothing here changes systemic choice, but ADT-free survival was 77% vs 60% at 4 years (HR 0·60) with median time off ADT beyond 48 months. For men who would otherwise be considered for ADT intensification on PSA doubling time, local therapy is competing for the same population.
8 details
Phase 2, open-label, randomised 1:1, investigator-initiated, 21 hospitals across Australia, Belgium, Italy, Norway, Spain and Switzerland. Recruited June 11, 2018 to April 30, 2021; median follow-up 50 months (IQR 42-58). Stratified by PET tracer (choline vs PSMA) and MDT type (sLND vs SBRT); participants and investigators unmasked.
Biochemical relapse after radical prostatectomy, postoperative RT, or definitive RT, with up to five PET-detected pelvic nodes (pelvis defined up to the aortic bifurcation, common iliac included). Bone, visceral, or above-bifurcation nodal disease excluded, as was previous RT overlapping current fields. Median age 70-71, median PSA at inclusion 1·00 vs 0·85 ng/mL, 91% and 86% EAU high-risk BCR, and 55-62% had a single positive node.
MDT arm: SBRT 30 Gy in 3 fractions every other day to 90% of the PTV with a 3 mm margin, or salvage lymph node dissection. ENRT arm: 45 Gy in 25 fractions to the whole pelvis on a modified RTOG 2009 template (upper limit L4-L5) with a simultaneous integrated boost to 65 Gy on PET-positive nodes; IMRT or rotational technique mandatory, with a benchmark-case QA programme. Prostate bed RT (≥66 Gy/33 fx) was advised for pT3-4, Gleason ≥8, or positive margins and given to 25% of MDT and 41% of ENRT pts.
Both groups received 6 months of LHRH agonist or antagonist, started no later than the first fraction (or day 1-10 postoperatively after sLND). Every patient who started intended local therapy plus ADT completed it. Physicians were instructed not to restart ADT absent clinical progression.
Primary: metastasis-free survival (any M1 on PET or death), with local or pelvic nodal relapse explicitly NOT counted as an event. Secondary: biochemical RFS, locoregional RFS, ADT-free survival, and late grade 2+ GU/GI toxicity to 48 months. OS, prostate cancer-specific survival, and time to castration resistance had insufficient events and are deferred.
Grade 2+ GU events above baseline at 4 years were 28% MDT vs 31% ENRT (absolute difference 3%, p=0·73) and grade 2+ GI 7% vs 9% (difference 2%, p=0·93). Most common grade 3 events were urinary incontinence (6% vs 10%) and diarrhoea (1% vs 2%). In post-hoc analysis the driver of toxicity was the prostate bed, not the pelvic volume: GI OR 4·6 (95% CI 1·5-15·8), p=0·0085 and GU OR 1·85 (0·95-3·60), p=0·068 with bed inclusion. No treatment-related deaths.
The single-arm GETUG-P07 OLIGOPELVIS reported 3-year bRFS of 45% for ENRT against 57% at 4 years here, though its median PSA was 3-4 ng/mL and staging was choline-based, so the populations differ. Against the ADT-intensification trials, EMBARK and PRESTO enrolled the PSA-doubling-time population that simulations put at up to 40% pelvic nodal relapse on PET, and this trial's median time off ADT exceeded 48 months in MDT and was not reached in ENRT, versus 13-18 months with RT alone and 16-17 months with ADT alone across earlier series.
No central PET review at baseline or follow-up, so the primary endpoint depends on local reads (authors cite κ 0·74 for pelvic nodes). Curves did not separate in year 1 because of the shared 6 months of ADT, which strains the proportional hazards assumption the HR summarises. The open-label design plausibly biased adverse-event attribution in both directions, and prostate bed RT was left to physician discretion, so a treatment that materially changed both toxicity and local recurrence was not randomised.
The result reads as a field-size question answered on pattern of failure rather than on distant control: relapse after MDT was predominantly locoregional, meaning PSMA PET missed nodal disease in at least half of pts treated to visible targets only. That reframes ENRT less as escalation than as compensation for imaging sensitivity that has not caught up with the treatment paradigm it enabled.
| Endpoint | MDT | ENRT | HR (80% CI) | p |
|---|---|---|---|---|
| MFS (1°) | 63% (56-69) | 76% (69-81) | 0·62 (0·44-0·86) | 0·063 |
| Biochemical RFS | 41% (34-47) | 57% (50-64) | 0·62 (0·48-0·80) | 0·014 |
| Locoregional RFS | 62% (55-69) | 85% (80-90) | 0·45 (0·31-0·65) | 0·0047 |
| ADT-free survival | 60% (53-67) | 77% (70-82) | 0·60 (0·43-0·83) | 0·049 |
CONSORT flow
Phase 2 powered at α=0·20; primary MFS p=0·063 would not clear conventional significance, and the authors themselves await a phase 3 (POINTER-PC).
- Does the MFS benefit hold at conventional significance in phase 3
- Is ENRT plus ADT better than intermittent ADT alone
- Should prostate bed RT be omitted when PSMA PET is bed-negative
📚 Sources · 📄 1 paper
The longer read
The number worth arguing about here is not the primary endpoint. MFS at 4 years favoured ENRT by 13 points with p=0·063, and the trial declares that positive only because α was prespecified at 0·20 with 80% CIs throughout. Read at conventional thresholds, the primary endpoint is a trend. What is not a trend is locoregional relapse-free survival, 85% versus 62%, HR 0·45, and the relapse table underneath it: pelvic nodal recurrence in 29% of the MDT group against 8% of the ENRT group. The trial's own logic runs from that finding to the primary one, since the authors attribute the MFS separation mainly to prevented M1a spread. If you accept that chain, the honest description is that treating the whole pelvis prevents nodal relapse, and that preventing nodal relapse buys some distant control whose size this trial cannot pin down.
The mechanistic reading matters more than the p value, because it is the part that generalises. Recurrence after MDT was predominantly locoregional, which is a statement about PSMA PET, not about SBRT. Nodes that were not visible at randomisation declared themselves later, and a one-time treatment aimed only at what the scan showed missed them in roughly half of pts. That is an imaging-sensitivity argument, and it is the reason the result should transfer to practices using the same tracers and the same field definitions, and the reason it might attenuate if imaging improves. It also suggests why the subgroup pattern falls where it does: benefit was largest at PSA below 1 (HR 0·27, interaction p=0·029) and with PSMA rather than choline staging, exactly the settings where occult disease is most likely to sit inside a pelvic field and least likely to sit outside it. That subgroup was post-hoc and the CIs are wide, so it is a hypothesis about who benefits, not a selection rule.
Against the comparators the trial names, the ENRT arm looks favourable rather than novel. GETUG-P07 OLIGOPELVIS reported 3-year bRFS of 45% for a similar field, but enrolled at median PSA of 3-4 ng/mL with choline staging, and neither difference can be separated from the treatment effect. The more useful comparison is to the ADT-intensification literature: EMBARK and PRESTO enrolled patients defined by PSA doubling time, a population simulations place largely within PET-detectable locoregional disease, and this trial reached a median time off ADT beyond 48 months in the MDT group and not reached in the ENRT group. Local therapy plus 6 months of ADT is competing with systemic escalation for the same men, and on deferral of long-term ADT it does not look worse.
Two design choices should move confidence downward. Prostate bed radiotherapy was advised by risk feature but left to physician discretion, and it was delivered to 25% of the MDT arm and 41% of the ENRT arm. In post-hoc analysis it drove grade 2+ GI events (OR 4·6) and probably GU events too, and separately associated with fewer local recurrences. A non-randomised co-intervention that is imbalanced between arms and affects both efficacy and toxicity sits uncomfortably inside a randomised comparison. Second, PET was read locally without central review, and the primary endpoint is defined entirely by PET. For ENRT to be wrong here, you would need either differential ascertainment of M1 disease between unmasked arms or a distant-control benefit that is entirely an artefact of shifting relapses from countable M1a nodes into an uncounted pelvic field. The locoregional data argue against the second, but neither is excluded by a phase 2 read at α=0·20, which is precisely why POINTER-PC exists.