Prostate
Mixed session: ENZARAD negative for enzalutamide, COMPPARE null for proton vs IMRT (spacer benefit exceeded modality effect), PROTEUS MFS data actively contested.
PROTEUS
ForBiochemically recurrent prostate cancer, post-radical prostatectomy
TL;DR53.0% (APA) and 60.7% (ADT) of MFS events PSMA PET-detected; APA+ADT vs ADT benefit in BCR prostate hotly contested.
6 details
- 🔍 Phase 3 RCT, APA + ADT vs ADT alone in BCR prostate cancer, post-RP setting
- 📊 Full primary endpoint data pending ASCO26 presentation; no effect size reported in source tweets
- 📊 NEJM paper: 53.0% (APA arm) and 60.7% (ADT arm) of distant mets identified by PSMA PET, not conventional imaging
- ⚠️ Majority of MFS events PSMA PET-only: magnitude of conventional-imaging MFS benefit unclear
- ⚠️ ASCO26 preview framing: 'some may call this a homerun, others may call this the largest negative'
- ❓ PSMA PET-detected MFS not an established OS surrogate; does EFS benefit translate to survival?
- Does PSMA PET-detected EFS/MFS benefit translate to OS?
- Magnitude of benefit by conventional imaging alone
📚 Sources · 🐦 3 tweets
#ASCO26
— Daniel E Spratt (@DrSpratticus) May 31, 2026
The PROTEUS trial results are now online...buckle up as we wait to see the full presentation. This is going to be a trial that is likely highly controversial until the full results are published.
Some may call this a homerun, others may call this the largest negative…
Thought experiment:
— Sean McBride (@seanmmcbride) May 31, 2026
Let's take a very simple hypothetical trial involving 100 patients in the APA arm and 100 patients in the ADT alone arm. Pulling from PROTEUS EFS data, assume that, by 5 years, 60 patients in the ADT arm have had a BCR compared to 50 in the ADT+APA arm.… pic.twitter.com/WJaiDlJnQs
#ASCO26
— Daniel E Spratt (@DrSpratticus) May 31, 2026
Talk about real-time updates. NEJM paper now online and my predictions and inferences appear true.
Majority of MFS events were by PET not conventional imaging. "Most distant metastases were identified by PSMA PET (53.0% of those in the apalutamide group and 60.7% in the… https://t.co/Yz4myY0flq
COMPPARE
ForDe novo localized prostate cancer, excluding very high risk and metastatic
TL;DRNo sig difference (bowel urgency 5.7% vs 6%, p=0.28; 3-yr BCF 98.0% vs 97.9%) between proton and IMRT in de novo localized prostate.
- vs PARTIQoL RCT: also null for bowel toxicity at 2yr in randomized proton vs IMRT; COMPPARE extends to larger N but non-randomized
| Outcome | IMRT (actual) | PT (actual) | p |
|---|---|---|---|
| Bowel urgency (EPIC) | 6% | 5.7% | 0.28 |
| Bowel frequency (EPIC) | 4% | 3.5% | 0.43 |
| ≥G2 GI toxicity (CTCAEv5) | 5.6% | 5.2% | 0.60 |
| 3-yr freedom from progression | 97.9% | 98.0% | 0.90 |
+2 more figures
| Group | 2-yr ≥G2 GI toxicity (95% CI) |
|---|---|
| IMRT, no spacer | 7.2% (5.0-9.9%) |
| Proton, no spacer | 8.7% (5.0-14%) |
| IMRT, spacer | 4.4% (2.8-6.4%) |
| Proton, spacer | 4.7% (3.6-6.0%) |
6 details
- 🔍 Prospective non-randomized comparative effectiveness study, N=2524, 51 PT + IMRT centers, Jul 2018-Oct 2022
- 🔍 De novo localized prostate cancer; very high risk and metastatic excluded; proton cohort 1500, photon 1000
- 📊 All 4 primary endpoints non-significant (p range 0.28-0.90); both modalities performed substantially better than hypothesized event rates
- 📊 Rectal spacers significantly reduced 2-yr ≥G2 GI toxicity regardless of modality (p=0.009, Gray's Test); spacer benefit exceeded modality effect
- ⚠️ Severely underpowered: hypothesized bowel urgency 15% (IMRT) vs actual 6%; study cannot establish equivalence at these event rates
- ⚠️ Non-randomized design; selection into proton vs IMRT may confound any toxicity signal
- Whether underpowering masks a real late toxicity advantage for proton therapy
- Role of rectal spacers in abrogating any modality-specific GI difference
- Long-term BCR and MFS as follow-up matures
📚 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
CAN-2409
ForHigh/intermediate-risk localized prostate cancer, RT 78Gy
TL;DRDFS HR 0.70 vs placebo (p=0.0155), driven by 2yr biopsy pCR 80.4% vs 63.6%; OS/PCSM immature at 50.3mo.
+1 more figure
7 details
- 🔍 Intra-prostatic oncolytic viral injection (CAN-2409) + RT 78Gy vs RT + placebo; randomized
- 📊 1° EP DFS: median NR vs 86.1mo, HR 0.70 (95% CI 0.52-0.94), p=0.0155
- 📊 2yr post-Rx biopsy pCR: 80.4% vs 63.6%
- 📊 2yr local persistence/recurrence: 19.6% vs 36.4%, p=0.0015
- ⚠️ DFS driven mainly by biopsy pCR (surrogate); MFS and BCR not reported in source
- ⚠️ OS and PCSM not significantly different; 1 PCSM event per arm at 50.3mo median f/u
- ⚠️ G3 tox <1% in both arms
- OS/PCSM benefit with longer follow-up?
- Role vs modern RT dose intensification (FLAME SIB 95Gy, ASCENDE-RT LDR-BT)?
- AI biomarker utility for guiding abiraterone in very high-risk non-metastatic PCa?
📚 Sources · 🐦 1 tweet
🗣️Prostate Oral Abstract #ASCO25
— Michael Serzan, MD (@MikeSerzanMD) June 3, 2025
👉Dr @angela_jia_ discusses "Better Treatments, Better Selection: Improving Patient Outcomes in Localized Prostate Cancer"
🔑 KEY TAKE AWAYS
- #CAN2409 improves DFS and 2yr PathCR however PCSM and OS remain immature.
❓How to integrate with… pic.twitter.com/WamsneYBI1
ENZARAD
ForHigh-risk localized PCa (Gleason 8-10, T3-4, or N1, or PSA ≥20 ng/mL), suitable
TL;DRMFS HR 0.88 (p=0.34), OS HR 0.87 (p=0.40); enzalutamide added to RT+2y ADT did not improve outcomes in high-risk localized PCa.
| Arm | Events/N | MFS 8y | HR (95% CI) | 2p |
|---|---|---|---|---|
| Enzalutamide | 98/401 | 74% | 0.88 (0.67-1.15) | 0.34 |
| Control (NSAA) | 109/401 | 72% | ref | ref |
+2 more figures
| Arm | Events/N | OS 8y | HR (95% CI) | 2p |
|---|---|---|---|---|
| Enzalutamide | 69/401 | 83% | 0.87 (0.63-1.20) | 0.40 |
| Control (NSAA) | 77/401 | 80% | ref | ref |
5 details
- 🔍 Phase 3 RCT (ANZUP), N=802, 1:1; high-risk localized PCa (Gleason 8-10, T3-4, N1, or PSA ≥20 ng/mL); median FU 8y
- 🔍 Enzalutamide 160mg/d x24mo + LHRH agonist x24mo vs NSAA x6mo + LHRH agonist x24mo; both arms: RT ± brachytherapy boost ± pelvic nodal RT
CONSORT flow
- 📊 Both 1° (MFS) and 2° (OS) endpoints not met; overall trial negative
- ⚠️ Pelvic RT and cN1 subgroup interactions are exploratory in a negative trial; hypothesis-generating, not sufficient for practice change
- ⚠️ ICECAP surrogacy framework cited validating MFS as OS surrogate; both concordantly null, no hidden OS benefit suggested
- Whether pelvic RT selection prospectively enriches for ARSI benefit in high-risk localized PCa
- Optimal ADT intensification strategy for cN1 high-risk prostate cancer
📚 Sources · 🐦 1 tweet
🚨ENZARAD at #ESMO25 presented by @DrPaulNguyen
— Pierre Blanchard, MD (@PBlanchardMD) October 19, 2025
No improvement in MFS or OS with the addition of enzalutamide to high dose radiotherapy + 2y ADT in high risk #prostatecancer
Possible benefit in cN1 pts or pts treated with pelvic RT. pic.twitter.com/vXLRKuIPeg
