onc brain

About · curated by Nick Boehling, MD · @nb2276

    Bladder

    7 studies across 5 dates

    2026-06-29

    BART

    ForHigh-risk pT3-4/N+/R+ MIBC, post-radical cystectomy + chemo

    TL;DR2-yr locoregional FFS 87.1% vs 76.0% (HR 0.43, p=0.04) favoring adjuvant RT post-cystectomy; OS not significant.

    Reported via UroToday →

    Why it mattersRadiation oncology

    The RT decision is adjuvant pelvic RT for the highest-risk post-cystectomy pts: benefit concentrates in N+ (HR 0.22) and T3+/N+ (HR 0.25), and RT cut isolated locoregional recurrence to zero (LR 8% vs 26%). Technique is standard 50.4 Gy/28 fx stoma-sparing IMRT, transferable; OS gain awaits the MERCY meta-analysis.

    Radiation Curative Phase 3 RCT Challenges SOC

    12 details 5 trials watching
    Methods
    • 🔍 Phase III RCT, N=153 (RT 77 / obs 76), accrued 2016-2024; largest RCT in this setting, stratified by nodal stage + chemo
    • 🔍 High-risk pT3-4/N+/R+ non-metastatic MIBC post-radical cystectomy; 62% pT3-4, 41% pN+, 28% variant histology, median age 57
    • 🔍 RT 50.4 Gy/28 fx stoma/bowel-sparing IMRT to cystectomy bed + pelvic nodes (iliac, presacral, obturator), daily IGRT
    • 🔍 Chemo neoadjuvant 71%, adjuvant 20%, none 9%; no immunotherapy in either arm
    CONSORT flow
    Randomized 153
    ↓
    Adjuvant RT
    allocated 77
    Observation
    allocated 76
    Results
    • 📊 2-yr outcomes, adjuvant RT vs observation (ITT)
      Endpoint (2-yr)RTObsHR (95% CI)p
      LRFFS (1°)87.1%76.0%0.43 (0.20-0.96)0.04
      DFS71.6%58.7%0.62 (0.36-1.05)0.07
      BCSS79.6%65.0%0.59 (0.33-1.10)0.09
      OS70.4%57.4%0.78 (0.49-1.26)0.31
    • 📊 Locoregional recurrence 8% (RT) vs 26% (obs), p=0.006; no isolated locoregional recurrences in the RT arm
    • 📊 2-yr LRFFS HR by analysis/subgroup (per-protocol 93.2% vs 75.0%)
      2-yr LRFFSHR (95% CI)
      ITT overall0.43 (0.20-0.96)
      Per-protocol overall0.27 (0.10-0.71)
      T3+ and N+0.25 (0.07-0.84)
      N+ disease0.22 (0.06-0.75)
    • 📊 Toxicity, adjuvant RT vs observation
      AERTObs
      Late G3+ toxicity8.4%10.5% (p=0.60)
      Acute G3 GI1.6%4.1%
      Acute G2 GI17.5%1.4%
    Critique
    • ⚠️ Underpowered ('fell short in sample size goal'); primary LRFFS CI 0.20-0.96 upper bound near 1, p=0.04 marginal
    • ⚠️ 14/77 RT-arm pts (refused 8, progressed 4, unfeasible 2) analyzed with observation; per-protocol HR 0.27 vs ITT 0.43
    • ⚠️ OS not significant (HR 0.78, p=0.31); benefit is locoregional control, OS awaits MERCY IPD meta-analysis
    • ⚠️ No IO tested; adjuvant nivolumab (Bajorin, NEJM 2021) now eligible, untested with/against RT
    Open questions
    📚 Sources · 📄 1 paper
    📄 PAPER · UroToday
    ASTRO 2025: Bladder Adjuvant Radiotherapy (BART): Clinical Outcomes from a Phase III Multicenter Randomized Controlled Trial
    article →
    Abstract
    ASTRO 2025 phase III Bladder Adjuvant Radiotherapy (BART), Advanced bladder cancer, cystectomy, advanced muscle invasive bladder cancer.
    📝 https://www.urotoday.com/conference-highlights/astro-2025/astro-2025-bladder-cancer/163510-astro-2025-bladder-adjuvant-radiotherapy-bart-clinical-outcomes-from-a-phase-iii-multicenter-randomized-controlled-trial.html

    2026-06-17

    INDIBLADE

    ForStage II/III cT2-4aN0-2 MIBC, including node-positive

    TL;DR2yr bladder-intact EFS 78% (67-90), OS 96% (91-100) with induction ipi/nivo then chemoRT in cT2-4aN0-2 MIBC.

    Why it mattersRadiation oncology

    Node-positive disease (N1-2) was eligible, so 78% 2yr bladder-intact EFS (67-90) extends the preservation pathway past the usual node-negative trimodality candidate. RT dose, fractionation, and radiosensitizer aren't in the source, so transferability to your CRT protocol is unverifiable. Moves the cystectomy-vs-bladder-preservation decision for IO-eligible MIBC.

    Combined Curative Phase 2 trial Early signal

    8 details 5 trials watching
    Methods
    • 🔍 Induction ipilimumab + nivolumab → concurrent chemoradiation (bladder-preservation intent)
    • 🔍 Eligibility: stage II/III cT2-4aN0-2 MIBC, includes N1-2 node-positive
    • 🔍 RT dose/fractionation + concurrent radiosensitizer not reported in source
    Results
    • 📊 1° EP: 2yr bladder-intact EFS 78% (95% CI 67-90%)
    • 📊 2yr OS 96% (95% CI 91-100%)
    Critique
    • ⚠️ Single-arm: can't isolate induction IO's contribution over chemoRT alone
    • ⚠️ Bladder-intact EFS is a composite surrogate; only 2yr f/u
    • ⚠️ N not reported in source tweet
    Open questions
    📚 Sources · 🐦 1 tweet

    2026-05-30 ASCO Annual Meeting 2026

    RAD-IO

    ForMuscle-invasive bladder cancer, cT2-T3, 13% node+, 75% prior neoadjuvant chemo

    TL;DR12-mo DFS 40/50 (80%) cleared the GO threshold for durvalumab added to 5FU/MMC chemoRT in muscle-invasive bladder, bladder-preservation intent.

    Why it mattersRadiation oncology

    RT-relevant extension is nodal coverage: node-positive pts (n=7) received 46Gy/20fx elective nodal RT plus 55Gy/20fx to bladder, pushing chemoRT bladder preservation past its usual node-negative limit. Dose is the hypofractionated BC2001 UK schedule (55Gy/20fx), not conventional fractionation, which gates transferability to US practice. Moves whether to add adjuvant IO and extend preservation to node+ MIBC.

    vs leading data
    • Contextual benchmark BC2001 (JCO 2016), DFS by chemo randomisation: HR 0.78 (0.60-1.02), p=0.07

    Combined Curative Phase 2 trial Early signal ASCO Annual Meeting 2026

    Primary outcome 12-mo DFS 40/50 (80%)
    Primary outcome 12-mo DFS 40/50 (80%)
    +1 more figure
    Completed planned treatment 33/54 (61%); discontinued early 21 (39%)
    Completed planned treatment 33/54 (61%); discontinued early 21 (39%)
    8 details 5 trials watching
    Methods
    • 🔍 Single-arm multi-stage feasibility/safety trial, N=55 (54 treated), MIBC, definitive bladder-preservation intent (Abstract 4504, ND James)
    • 🔍 RT: 55Gy/20fx to bladder; node-positive pts add 46Gy/20fx elective nodal RT (Stage 1 expansion, first 6 node+ pts)
    • 💊 ChemoRT backbone: concurrent 5-FU + mitomycin C (BC2001 regimen)
    • 💊 Durvalumab neoadjuvant, synchronous with chemoRT, then adjuvant for 12 months
    • 🔍 Population (n=55)
      • cT2 44/55 (80%), cT3 11/55 (20%)
      • Node+ 7 (13%): N1 4, N2 3
      • Prior neoadjuvant chemo 41 (75%)
      • Age 69 (IQR 62-76), male 45/55 (82%)
    Results
    • 📊 1° outcome: 12-mo DFS 40/50 (80%), 95% CI 0.67-0.89, cleared pre-set GO threshold (≥75%) for further evaluation
    Critique
    • ⚠️ Single-arm, benchmarked vs historical BC2001; no contemporaneous chemoRT-alone or durvalumab-omission arm, so the IO contribution can't be isolated
    • ⚠️ 12-mo DFS is an early surrogate; bladder-intact survival, OS, and late GU/GI toxicity not reported in source
    Open questions
    📚 Sources · 🐦 3 tweets

    Perioperative MIBC: Management Post-pCR

    TL;DR85% 5-yr OS with pT0 (SWOG 8710) makes pCR strongly prognostic, yet sandwich IO regimens continue planned adjuvant therapy regardless of response.

    Trials discussed

    SWOG 8710ABACUSCHECKMATE-274KEYNOTE-905VOLGANIAGARAVESPERKEYNOTE-B15

    vs leading data
    • High-risk staging (≥ypT2/N1) after neoadjuvant chemo is an adjuvant indication (CHECKMATE-274)

    Combined Curative ASCO Annual Meeting 2026

    Periop EVP (KEYNOTE-905) vs RC alone: OS HR 0.50, median OS 41.7 mo
    Periop EVP (KEYNOTE-905) vs RC alone: OS HR 0.50, median OS 41.7 mo
    +1 more figure
    Perioperative MIBC: Management Post-pCR
    8 details 4 trials watching
    Methods
    • 🔍 pCR is registrational only as a phase 3 co-primary; standalone use limited to phase 2 signal-seeking
    • 🔍 KEYNOTE-905 schedule: 3 cycles EVP, cystectomy, then 6 cycles EV + 14 cycles pembro
    • 💊 For sandwich IO regimens, planned adjuvant therapy continues regardless of pathologic response
    • 💊 Post-pCR adjuvant continuation by regimen
      • NIAGARA: resume durvalumab for 8 months post-cystectomy
      • Periop EVP: resume EVP post-cystectomy
      • Cisplatin chemo alone: surveillance after pCR is standard
    Results
    • 📊 pCR (pT0N0) after neoadjuvant chemo is strongly prognostic: SWOG 8710 shows 85% 5-yr OS if pT0
    • 📐 Meta-analysis: pooled RR 0.19 for RFS favoring pCR
    • 📊 Perioperative regimens by cisplatin-eligibility
      TrialSettingKey result
      KEYNOTE-905Cis-ineligible, periop EVP vs RC aloneOS HR 0.50; now standard (FDA approved)
      VOLGACis-ineligible, preop EV + periop durva/tremeImproved EFS (press release)
      NIAGARACis-eligible, preop Gem/Cis + periop durva24-mo OS 82.2% vs 75.2%
      VESPERCis-eligible, ddMVAC vs Gem/Cis5-yr OS 66% vs 57%; more toxicity
      KEYNOTE-B15Cis-eligible, periop EVP vs Gem/CisImproved OS; under FDA review
    Critique
    • ⚠️ Not all pts in perioperative trials completed adjuvant therapy, sometimes due to toxicity
    Open questions
    📚 Sources · 🐦 1 tweet

    GU Curative Intent: Living Longer, Living Better

    TL;DRDiscussant roundup balancing cure vs function: durvalumab+chemoRT kept full bladder RT delivery; EV+pembro bladder-sparing (EV309 vs chemoRT) and ctDNA RCC selection maturing.

    Trials discussed

    EV209EV309RAMPART

    Why it mattersRadiation oncology

    The radonc read is bladder preservation under competition: durvalumab added to 55Gy/20fx MMC/5-FU chemoRT kept full RT delivery in 54/54 pts (87% without delay), but EV309 now randomizes EV+pembro against chemoradiotherapy itself. If systemic bladder-sparing matures, trimodality's role narrows.

    vs leading data
    • Adjuvant RCC ctDNA (Choueiri, ASCO 2026): ctDNA status refines selection beyond pathologic features; ctDNA-positive pts had substantially shorter DFS

    Curative ASCO Annual Meeting 2026

    GU Curative Intent: Living Longer, Living Better
    RT/chemo deliveryn (%)
    Full 55 Gy/20 fx RT54 (100)
    No RT extension/delay47 (87)
    5-FU week 4 administered42 (78)
    Chemo discontinued early12 (22)
    Durvalumab completed33 (61)
    Durvalumab discontinued early21 (39)
    +1 more figure
    GU Curative Intent: Living Longer, Living Better
    8 details 4 trials watching
    Methods
    • 🔍 ASCO 2026 GU discussant summary (Brian Rini): curative-intent bladder + RCC, framed as improving cure while preserving function/QoL
    • 🔍 EV+pembrolizumab bladder-sparing trials in MIBC (EVP)
      EV209EV309
      PopulationCystectomy-eligibleCystectomy-ineligible/refusing
      StagecT2-4a MIBCcT2-4a MIBC
      N240390
      Regimen9 cycles EV + 1 yr pembrolizumab9 cycles EV + 1 yr pembrolizumab
      Designsingle-armrandomized vs chemoradiotherapy
      EndpointscCR, 2 yr BIEFSBIEFS, OS
    Results
    • 📊 Bladder preservation arm: durvalumab added to 55 Gy/20 fx chemoRT (mitomycin C + 5-FU backbone)
    • 📊 Per Rini: durvalumab didn't compromise RT delivery, and chemo delivery not significantly compromised
    Critique
    • ⚠️ Deliverability-only readout (N=54); long-term bladder preservation, function, symptom burden, safety and QoL still require follow-up (Rini)
    • ⚠️ EV309 randomizes EV+pembrolizumab against chemoradiotherapy, directly pitting systemic bladder-sparing against trimodality
    • ⚠️ RAMPART non-clear cell RCC subgroups: few pts/events, wide CIs, point estimates unstable; central pathology review ongoing
    • ⚠️ Adjuvant IO has no proven benefit in non-clear cell RCC (per Rini)
    Open questions
    📚 Sources · 🐦 1 tweet

    2026-05-21

    Bladder Adjuvant Radiotherapy Phase III

    ForHigh-risk MIBC post-cystectomy (T3-4, N+, margin+, or ≤10 nodes)

    TL;DR2yr LRFS 87.1% vs 76.0%, HR 0.43 (0.20-0.96) p=.04 favoring adjuvant pelvic IMRT in high-risk MIBC post-cystectomy.

    Why it mattersRadiation oncology

    Actionable RT detail is technique: stoma-sparing IG-IMRT 50.4Gy/28fx to bed + pelvic nodes delivered the locoregional gain with no added severe toxicity, so it transfers cleanly. The gradient matters: DFS, BCSS, and OS all favored RT yet none reached significance (N=153), moving the offer-adjuvant-RT decision short of a proven survival benefit.

    vs leading data
    • vs Zaghloul (Egypt NCI RCT): prior adjuvant-RT benefit was in an SCC/bilharzial-enriched cohort; this trial extends the signal to urothelial with modern IMRT

    Radiation Curative Phase 3 RCT Confirmatory

    8 details 3 trials watching
    Methods
    • 🔍 Phase III multicenter RCT, N=153 (RT=77, Obs=76); stratified by nodal status + chemo timing
    • 🔍 RT: stoma-sparing IG-IMRT 50.4Gy/28fx to cystectomy bed + pelvic nodes
    • 🔍 Eligibility: high-risk post-RC (any of T3-4, N1-3, margin+, ≤10 nodes dissected); 62% pT3-4, 41% pN+
    • 💊 >90% had perioperative chemo (71% neoadjuvant, 20% adjuvant); none received immunotherapy
    • 🔍 RT contribution is clean: both arms had RC + perioperative chemo, so RT vs observation isolates the radiation effect
    CONSORT flow
    Randomized 153
    ↓
    Adjuvant RT
    allocated 77
    Observation
    allocated 76
    Results
    • 📊 Outcomes by arm (RT vs Obs), median f/u 47mo
      EndpointRTObsHR (95% CI)
      LRFS (2yr)87.1%76.0%0.43 (0.20-0.96), p=.04
      DFS71.6%58.7%0.62 (0.36-1.05)
      BCSS79.6%65.0%0.59 (0.33-1.10)
      OS70.4%57.4%0.78 (0.49-1.26)
    • 📊 No additional severe toxicity with RT; late GU/GI grades not detailed in source
    Critique
    • ⚠️ Underpowered for survival: every secondary (DFS, BCSS, OS) favored RT but all CIs cross 1
    Open questions
    📚 Sources · 📄 1 paper
    📄 PAPER Murthy; Maitre; Pal et al. · Journal of clinical oncology : official journal of the American Society of Clinical Oncology (2026-05)
    Bladder Adjuvant Radiotherapy: Phase III Multicenter Randomized Controlled Trial of Adjuvant Radiotherapy or Observation for Postcystectomy Muscle-Invasive Bladder Cancer.
    PMID 42166701 → doi
    Abstract
    PURPOSE: To report the primary analysis of a multicenter, phase III randomized trial of adjuvant radiotherapy (RT) after chemotherapy and radical cystectomy (RC) in patients with high-risk muscle-invasive bladder cancer (MIBC).<br/><br/>METHODS: Patients with nonmetastatic urothelial MIBC at high risk after RC (any one of: T3-4, N1-3, margin positive, &#x2264;10 nodes dissected) were randomly assigned 1:1 to adjuvant RT or observation (Obs), stratified by nodal involvement (yes/no) and chemotherapy (neoadjuvant/adjuvant/none). Stoma-sparing IG-IMRT 50.4Gy in 28 fractions was prescribed to the cystectomy bed and pelvic nodes. The primary end point was 2-year locoregional recurrence-free survival (LRFS), and the secondary end points were disease-free survival (DFS), bladder cancer-specific survival (BCSS), and overall survival (OS).<br/><br/>RESULTS: From June 2016 to May 2024, 153 patients were randomly assigned (Obs = 76, RT = 77), with 62% and 41% of patients having pT3-T4 and pN+ stages, respectively. Over 90% of the patients received systemic chemotherapy (71% neoadjuvant and 20% adjuvant), and none received immunotherapy. After a median follow-up of 47 months, the 2-year LRFS was significantly higher with adjuvant RT versus observation (87.1% v 76.0%, hazard ratio [HR], 0.43 [95% CI, 0.20 to 0.96], P = .04). The DFS was 71.6% versus 58.7% (HR, 0.62 [95% CI, 0.36 to 1.05]), BCSS was 79.6% versus 65.0% (HR, 0.59 [95% CI, 0.33 to 1.10]), and OS was 70.4% versus 57.4% (HR, 0.78 [95% CI, 0.49 to 1.26]) for RT and Obs, respectively.<br/><br/>CONCLUSION: Adjuvant pelvic IMRT after radical cystectomy and perioperative chemotherapy suggests an improvement in locoregional control in patients with high risk urothelial MIBC with no additional severe toxicity.

    2026-05-19

    Bladder-preserving TMT for MIBC (ESTRO 2026)

    ForNon-metastatic MIBC (cT2-T4a N0M0), median age 76

    TL;DRCLR 63.7% with trimodality therapy in MIBC; complete local response linked to lower local recurrence and better survival in a 369-pt Spanish cohort.

    Why it mattersRadiation oncology

    Image guidance and chemo regimen, not just patient selection, move local control: weekly portal imaging (older 2D IGRT) cut CLR odds (OR 0.35, p<0.001) while 5-FU-based CRT raised them (OR 4.9, p=0.038), VMAT trending favorable. For an RT reader, this argues for conformal daily-IGRT delivery and a 5-FU backbone when offering bladder-preserving TMT.

    vs leading data
    • No randomised comparator vs radical cystectomy; authors frame survival as comparable to international TMT series

    Combined Curative Retrospective Confirmatory

    8 details 2 trials watching
    Methods
    • 🔍 Multicenter retrospective cohort, Spain 2010-2022; N=369 cT2-T4a N0M0 MIBC, median age 76, 85.1% male
    • 🔍 TMT = maximal TURBT + concurrent chemoRT; 1° EP complete local response (CLR), predictors by multivariable logistic regression
    • 🔍 VMAT trended toward favorable outcomes (not statistically significant)
    Results
    • 📊 CLR 63.7%
    • 📊 Disease progression 28.8%, by pattern
      • Local 10.1%
      • Systemic 10.7%
      • Combined 8.7%
    • 📊 Salvage cystectomy 9.7%
    • 📐 Predictors of CLR (multivariable logistic regression) — comparison values omitted (cell value "0.038" not verified in source)
    Critique
    • ⚠️ Key caveats
      • Retrospective: TMT-selected pts likely fitter / lower-burden than RC candidates (selection bias)
      • CLR is a surrogate; OS/CSS listed as secondary but no effect size in source
    Open questions
    📚 Sources · 🐦 1 tweet