POP-RT vs PEACE-2
TL;DRWPRT bFFS HR 0.50 (POP-RT) vs bPFS HR 0.97 (PEACE-2); pelvic RT benefit vanishes with 3yr ADT, PSMA staging.
POP-RTPEACE-2
The reversal tracks four coupled changes, and the one an RT reader controls is target volume: with 36 months ADT, 78 Gy EQD2 and PSMA staging, WPRT bought nothing biochemically (HR 0.97, p=0.73) where it halved biochemical failure at 24 months ADT and 74-76 Gy (HR 0.50). This moves elective nodal coverage toward optional in PSMA-staged very-high-risk N0M0 on 3 years of ADT, not in conventionally staged pts.
In very-high-risk N0M0 prostate staged by PSMA PET and planned for 36 months ADT with dose-escalated RT, this questions routine whole-pelvis coverage; it does not extend to conventionally staged pts or shorter ADT, where POP-RT still supports it.
Target volume is the variable you own here. WPRT halved biochemical failure at 24 months ADT and 74-76 Gy EQD2 (HR 0.50) but returned HR 0.97 (p=0.73) at 36 months ADT, 78 Gy and PSMA staging, with no toxicity penalty either way. Elective nodal coverage becomes conditional on staging and ADT length, not automatic.
ADT duration is the confounder doing the heavy lifting: 24 vs 36 months separates the two trials as much as the RT volume does. If 3 years of ADT is what erases the nodal-RT signal, then shortening ADT for tolerability reopens the case for pelvic coverage, so the systemic and RT decisions cannot be made independently in very-high-risk N0M0.
| Endpoint | POP-RT HR (95% CI), p | PEACE-2 HR (95% CI), p |
|---|---|---|
| bFFS / bPFS | 0.50 (0.42-0.61), p<0.001 | 0.97 (0.81-1.16), p=0.73 |
| cFFS / cPFS | 0.74 (0.61-0.90), p=0.002 | 0.81 (0.63-1.03), p=0.09 |
| MFS | 0.72 (0.58-0.89), p=0.002 | 0.93 (0.74-1.17), p=0.54 |
8 details 4 trials watching
Two independent phase III, open-label, randomized trials of whole-pelvis RT vs prostate-only RT, set side by side in a curator comparison graphic. POP-RT accrued 2011-2016 (median f/u 6.3-7.2 yr, updated); PEACE-2 accrued 2018-2023 and reads out at ~5.5 yr median f/u as an interim analysis (ESTRO 2026).
POP-RT enrolled high / very-high-risk localized N0M0 disease staged by conventional CT and bone scan. PEACE-2 restricted to very-high-risk N0M0 with PSMA PET/CT widely used, so its N0 is a cleaner, node-negative-by-molecular-imaging population.
Both delivered IMRT to whole pelvis plus prostate boost against prostate-only IMRT. Prostate dose was 74-76 Gy EQD2 in POP-RT and 78 Gy EQD2 in PEACE-2, so the control arm in the newer trial is the better-treated prostate.
ADT was a GnRH analog plus antiandrogen in both, but 24 months in POP-RT vs 36 months in PEACE-2. The extra year of systemic control is the single most plausible eraser of a nodal-RT effect.
Primary: bFFS in POP-RT, biochemical PFS in PEACE-2. Secondaries overlap (clinical failure/progression, MFS, OS, toxicity), with PEACE-2 adding CSS. The endpoints are close analogues but not identically defined, which limits how tightly the HRs can be compared.
Both trials reported comparable Grade ≥2 late GU toxicity between arms, with no significant increase in toxicity from WPRT in either. Toxicity is therefore not the lever in this decision; efficacy is.
POP-RT remains the only randomized trial to show a clear elective pelvic RT benefit (bFFS HR 0.50, MFS HR 0.72). PEACE-2's null biochemical result (HR 0.97) at interim is the first randomized read to contradict it, and it does so with a systemic and staging backbone POP-RT never had.
The two trials differ simultaneously in ADT duration, prostate dose, staging modality, risk band and accrual era, so no single factor can be assigned the loss of effect. PEACE-2's read is also interim with shorter follow-up than POP-RT's, and biochemical endpoints mature earliest, so the later endpoints are the least settled.
The graphic's own reading is that longer ADT, modern staging and intensified local therapy may reduce the incremental benefit of elective pelvic RT in very-high-risk disease. That is a hypothesis this comparison cannot test: it settles nothing about which of the four changes did the work, and a reader who shortens ADT while omitting pelvic RT is borrowing from both trials at once.
| Endpoint | POP-RT | PEACE-2 |
|---|---|---|
| Biochemical (bFFS / bPFS) | HR 0.50 (0.42-0.61), p<0.001 | HR 0.97 (0.81-1.16), p=0.73 |
| Clinical (cFFS / cPFS) | HR 0.74 (0.61-0.90), p=0.002 | HR 0.81 (0.63-1.03), p=0.09 |
| MFS | HR 0.72 (0.58-0.89), p=0.002 | HR 0.93 (0.74-1.17), p=0.54 |
- Does PEACE-2's cPFS signal mature into benefit at final analysis?
- Is longer ADT or PSMA staging the reason pelvic RT stopped working? n=250 · primary completion 2031-05 · PSMA-N0M0 randomised to PORT vs prostate+WPRTrecruiting Abi/Pred + ADT vs ADT in PSMA-Positive, Conventionally Node-Negative Prostate Cancer Phase 2n=140 · primary completion 2033-04 · PSMA+ cN0 nodes: ADT vs abi/pred intensification
- Does elective pelvic RT still help pts on shorter ADT? recruiting Phase II Trial of PSA Response-based Androgen Deprivation Therapy and Nodal Coverage for Prostate Cancer Early Salvage Radiotherapy (RANGER) Phase 2n=68 · primary completion 2030-11 · adds pelvic nodal RT + 4mo ADT in PSA nonrespondersn=250 · primary completion 2031-05 · prostate-only vs whole-pelvis RT, high-risk N0
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POP RT Vs PEACE II
— Rohit Malde (@roxboxfix) May 18, 2026
2 years ADT + WPRT
Vs 3 years ADT + Prostate Only RT
Tough to choose or you already have a choice ?? pic.twitter.com/42kdSKQYKW
The longer read
The value of this side-by-side is that it isolates a real disagreement between two randomized trials asking the same question, and then makes clear why the disagreement cannot be resolved from the numbers on the slide. POP-RT halved biochemical failure with whole-pelvis RT (HR 0.50, 0.42-0.61) and carried that through to MFS (HR 0.72, 0.58-0.89). PEACE-2, at interim, reports a biochemical HR of 0.97 (0.81-1.16) and an MFS HR of 0.93 (0.74-1.17). Those confidence intervals do not overlap on the biochemical endpoint, so this is not two trials agreeing with different precision; it is a genuine reversal.
Four things changed at once, and each has a plausible mechanism. ADT went from 24 to 36 months, and a third year of castration suppresses exactly the micrometastatic nodal disease elective pelvic RT is meant to sterilize. Staging went from CT and bone scan to PSMA PET/CT used widely, which removes from the N0 stratum a share of pts who actually harbored nodal disease, the very pts in whom POP-RT's benefit most plausibly concentrated. Prostate dose rose from 74-76 to 78 Gy EQD2, improving the control arm rather than the experimental one. And the risk band narrowed to very-high-risk only. Any of these could produce a null; the design cannot tell you which did, and a cross-trial HR comparison carries no interaction test.
Methodologically, the asymmetry in maturity should move confidence in a specific direction rather than uniformly. PEACE-2 is an interim analysis at roughly 5.5 years against POP-RT's updated 6.3-7.2 years. Biochemical endpoints mature first, so the null biochemical result is the most trustworthy thing PEACE-2 currently reports, and it is the endpoint where the reversal is starkest. Conversely, the borderline clinical progression signal (HR 0.81, p=0.09) is the least settled number here and should not be read as a benefit waiting to declare itself; at interim, with no multiplicity control described, that p-value is a reason to wait rather than a reason to treat.
What should a radiation oncologist do with this. The honest read is that elective nodal coverage has become a conditional decision rather than a default. In a pt staged conventionally, or one who will not receive three years of ADT, nothing here undercuts POP-RT, and the magnitude there is large enough that omitting the pelvis is a real gamble. In a PSMA-staged very-high-risk N0M0 pt committed to 36 months of ADT with a dose-escalated prostate, PEACE-2 says the pelvis adds no measurable biochemical benefit, and since both trials found no excess Grade ≥2 late GU toxicity from WPRT, the argument for omission is efficacy futility rather than toxicity avoidance.
The way this could be wrong is if PEACE-2's benefit is real but deferred. Nodal recurrence expressed as clinical rather than biochemical failure would show up late, and the cPFS HR of 0.81 is at least compatible with that. The final analysis, with CSS and OS, is the number that settles it. Until then, the safest inference is the narrow one: intensified systemic and local therapy plus better staging shrinks the space in which pelvic RT earns its place, without abolishing it.