Decipher and PAM50 in NRG/RTOG 9601 and 0534
TL;DRASTRO 2026 secondary analyses: Decipher prognostic in 9601 but not formally predictive; PAM50 luminal-B predicted STADT benefit with salvage RT in 0534.
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NRG/RTOG 9601NRG/RTOG 0534NRG-GU006NRG GU-009
The actionable split is early salvage with low Decipher: no significant 15-yr PCSM benefit from bicalutamide, while late salvage benefited regardless of score. PAM50 luminal-B status, reported on the Decipher grid, adds a predictive read for STADT. The PLNRT-by-subtype MFS trend is exploratory and should not yet move pelvic nodal coverage decisions.
In a post-RP pt with early salvage PSA and Decipher ≤0.6, this questions the PCSM value of adding hormone therapy to salvage RT; it does not extend to late salvage pts, who benefited regardless of score.
For salvage prostate bed RT, low-Decipher early salvage pts showed no significant PCSM gain from adding bicalutamide, while late salvage benefited regardless. A PAM50 luminal-B trend toward PLNRT benefit on MFS appeared in 0534 but is exploratory and does not support changing nodal fields.
PAM50 luminal-B predicted benefit from STADT in 0534 (significant interaction), matching NRG-GU006 with apalutamide, which suggests the effect does not depend on the agent. Decipher stayed prognostic but did not meet the predictive criterion, so it refines absolute risk rather than identifying who responds to ADT.
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Two ASTRO 2026 secondary biomarker analyses of randomized salvage trials, discussed in a UroToday interview. RTOG 9601: salvage RT ± bicalutamide 24 mo. RTOG 0534: PBRT vs PBRT + STADT vs PBRT + STADT + PLNRT, PAM50 on a subset.
Post-prostatectomy salvage pts. 9601 enrolled PSA 0.2 to 4.0, early and late salvage. The 0534 PAM50 subset showed no significant baseline differences across arms.
Decipher was prognostic for OS, PCSM and DM, including early salvage, but not predictive by the statistical criterion. In 0534, luminal-B pts gained a large FFP benefit from STADT vs much less in non-luminal-B, with a significant interaction p.
| Salvage setting | Decipher | PCSM benefit at 15 yr |
|---|---|---|
| Early salvage | >0.6 | >5% |
| Late salvage | Any | >5% |
| Early salvage | Low (≤0.6) | No significant benefit |
The PAM50 finding matches NRG-GU006, where luminal-B tumors benefited from apalutamide, so the signal holds across bicalutamide, leuprolide-based STADT and an ARPI. NRG GU-009/010 used a Decipher cut of 0.85 in the intact setting, vs 0.6 here post-op.
No HRs, interaction p-values or absolute rates are given in the source interview. The PSA threshold separating early from late salvage is not stated. Decipher and PAM50 can be discordant, and the source offers no data on how to resolve that.
Presenters frame both tests as one input to shared decision-making with pts, not a gate. Decipher reports PAM50 subtype on the same grid, so a single order yields both.
- Does PAM50 luminal-B status predict benefit from pelvic nodal RT?
- How to act on discordant Decipher and PAM50 results
- Optimal Decipher cut point for de-intensifying ADT in early salvage
📚 Sources · 📄 1 paper
Abstract
The longer read
The two abstracts answer different questions, and it helps to keep them apart. Decipher in RTOG 9601 is a risk discriminator: it sorts pts by how likely they are to metastasize or die of prostate cancer, with treatment-adjusted models that hold in the early salvage subgroup most US pts now fall into. What it did not do is clear the bar for prediction, meaning the relative benefit of bicalutamide did not differ by score in a statistically convincing way. The decision tree, which finds no significant PCSM benefit only in early salvage with low Decipher, is therefore an absolute-risk argument. Low-risk pts have little to gain in absolute terms, even if the relative effect is constant. That is a legitimate basis for de-intensification, but it is a different claim from saying the drug does not work in that group.
PAM50 makes the stronger mechanistic claim. In the 0534 subset, the luminal-B versus non-luminal-B interaction for STADT benefit on FFP was significant, and the direction matches NRG-GU006 with apalutamide and earlier retrospective cohorts. Agreement across three hormone strategies is the most persuasive part of the story, because it argues the subtype is reading androgen dependence rather than the behavior of one agent. The caveat is sample: only part of 0534 had evaluable tissue, and the presenter repeatedly cautioned that most p-values were modest and the endpoints imperfect.
For the RT reader, the PLNRT observation is the tempting one and the least supported. An MFS trend by subtype between the nodal and no-nodal arms, absent on FFP and not significant, is a hypothesis for a future trial, not a field-size criterion. Nothing here should change who gets pelvic nodes.
Two practical gaps stand out. The cut points do not transfer: 0.6 was the 9601 dataset median, while GU-009/010 used 0.85 in intact disease, so a single universal Decipher threshold does not exist. And discordance between a high Decipher score and a non-luminal-B call is acknowledged without data on how to resolve it. Without published effect sizes, interaction p-values or the PSA cut separating early from late salvage, the reasonable read is that these tools refine counseling in salvage RT and point toward subtype-directed trials. They do not yet replace PSA and clinical risk as the backbone of the ADT decision.