Endowed Professor, Surgeon, Former Fellowship Director @UTMDAnderson | President @IBCG_BladderCa | Assoc Editor @EurUrolOncol | Views my own
Houston, TX
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20 years ago, IBCG started with a small group around a table.
Later this month, friends and colleagues from around the world gather in Houston for #IBCG26. Two days around the table tackling some of the hardest questions in #BladderCancer, debating the evidence and challenging each other on where we go next.
Looking forward to seeing you all!
@UrogerliMD @spsutkaMD @LAUrology_NL @shilpaonc @mouwlab @pjhensley11 @AndreaNecchi @AmirHorowitz @PGrivasMDPhD @karima_oualla @SimaPorten @joanfundi @marigfern
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Deeply honored to receive the IBCN Lifetime Achievement Award.
This one is particularly special. IBCN has been a big part of my life for many years, and many colleagues have become close friends along the way.
And receiving it from @pcvblack made it even better. I used to evaluate him. Now apparently he gets to evaluate my lifetime! (His AI skills, however, remain a work in progress).
Thank you to everyone who has been part of the journey. Although, as I said tonight, I certainly hope the “achievement” part isn’t over yet! 😊
#BladderCancer #IBCN @IBCN1997 @mouwlab @LDyrskjot @WesKassouf #OncSurgery @IBCG_BladderCA @UTMDAnderson
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Ashish M. Kamat, MD, MBBS retweeted
Practical pathways for delivering new #BladderCancer therapies in community #urology. @HafronJason joins @UroDocAsh explaining how independent urology practices can reliably adopt new intravesical bladder cancer therapies, using gemcitabine intravesical system (TAR-200) that carries a J-code, as the primary example for BCG-refractory disease. #WatchNow > bit.ly/4huY6pr
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This resonates. One lesson I’ve learned over the years: build your own support network, both inside and outside the work environment.
It matters more than you think.
@PGrivasMDPhD @nnavai @shilpaonc @montypal @UrogerliMD @SpiessPhilippe @siadaneshmand @HenryKuerer
Some thoughts on burnout: 🧵
A part of burnout in medicine, especially in academia, is that people are carrying around with them an enormous number of thoughts and frustrations that just sit there and fester in their minds, and they see no safe outlet for expressing them.
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The dream team! Congratulations @NehaVapiwala.
Heartiest Congratulations to the amazing @NehaVapiwala on this richly deserved honor!
Neha, you are such an inspiration for everyone around you, especially women in #STEM including me.
@AparnaKamatMD @karima_oualla @giannatempopatr @ASTRO_org @UroDocAsh @WeAreWLO @fumikochino @MoningiShalini @MKnoll_MD
There's a new version of this post
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Spot-on analysis. We assume that NECTIN4 is near ubiquitous, but if we want true precision with ADCs in urothelial cancer, surface availability and target dynamics have to replace broad-brush “positivity”.
Looking forward to the prospective readouts and implications for bladder sparing selection.
@IBCG_BladderCA @PGrivasMDPhD @AndreaNecchi @shilpaonc @UrogerliMD @DrRosenbergMSK
The NECTIN4 biomarker signal was already there.
We were quite surprised when revisiting the pivotal EV-301 data: higher NECTIN4 expression was already significantly associated with response to enfortumab vedotin — ORR 45.8% vs 20.0%.
At the time, this was not the prevailing view: EV was considered effective largely irrespective of NECTIN4 expression.
One possible explanation is how NECTIN4 was measured. The unusually high expression levels in EV-301 suggest that overall/combined staining may have captured both membranous and cytoplasmic NECTIN4, potentially diluting the biologically relevant signal.
Our new data show clearly:
🎯 Membranous NECTIN4 predicts EV response and survival. Cytoplasmic NECTIN4 does not.
This makes sense mechanistically: an ADC needs an accessible cell-surface target to bind and deliver its payload
-> well established eg for HER2 (Tumor agnostic approval in HER2 3+)
Since EV-301, the evidence supporting membranous NECTIN4 as a biomarker has continued to grow — including independent EV+pembrolizumab data and now other NECTIN4-targeting ADCs such as SHR-A2102.
The next step is prospective validation. Our EVOKE trial is fully enrolled — stay tuned.
And perhaps the most important question: Can we improve outcomes for NECTIN4-low tumors by selecting a different target, payload or therapeutic strategy?
This is where ADCs should be heading: from target expression to true precision oncology
@Markuseckstein3 @DrRosenbergMSK @Dr_Aggen
#DGU26 @amerseburger @dgukongress @DGUrologie
@OncoAlert @weoncologists @urotoday @DrChoueiri @PTarantinoMD @raffcolo @tompowles1 @UroDocAsh @Uromigos @imedverse @CCR_AACR @Uroweb @PGrivasMDPhD @montypal @apolo_andrea @AndreaNecchi @DrYukselUrun
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Ashish M. Kamat, MD, MBBS retweeted
IBCG Risk Stratification Model for Intermediate-Risk NMIBC from @UroDocAsh: myopenmedicine.com/algorithm…
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Ashish M. Kamat, MD, MBBS retweeted
Phase II trial of neoadjuvant sasanlimab and SBRT as an in situ vaccine in cisplatin-ineligible #MIBC. @DrRajSat @MethodistHosp joins @UroDocAsh @UTMDAnderson to discuss the RAD VACCINE MIBC phase II trial combining sasanlimab with stereotactic radiation for cisplatin-ineligible muscle-invasive bladder cancer. #WatchNow on UroToday > bit.ly/4wNVnfq
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Ashish M. Kamat, MD, MBBS retweeted
Phase III trial compares BCG strains and priming in #NMIBC. Robert Svatek, MD, MSCI @UTHealthSA sits down with @UroDocAsh @UTMDAnderson to discuss this three-arm trial comparing Tokyo versus TICE BCG strains with priming arm in non-muscle-invasive bladder cancer. Dr. Svatek aims to secure FDA approval for Tokyo strain to address ongoing BCG shortages despite manufacturing challenges. #WatchNow on UroToday > bit.ly/4fByQMN
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Ashish M. Kamat, MD, MBBS retweeted
Our NECTIN4 scoring system for predicting enfortumab vedotin response in urothelial carcinoma is just published. 🔬
The short version: NECTIN4 is not a failed biomarker. It has been measured in the wrong compartment.
📊 179 EV-treated mUC patients, multicenter, FISH plus IHC, benchmarked against EV-301 EPAR data.
Why the field thought NECTIN4 was ubiquitous 🧠
In EV-301 the median H-score was 250, with 82.6% ≥150. That near-universal expression underpinned the biomarker-unselected label.
In our cohort, membranous H-score alone was 160. Cytoplasmic was 200. Combined, 260, with 78.2% ≥150, almost exactly mirroring EV-301.
So the trial numbers most likely reflect membranous plus cytoplasmic staining. That single methodological choice is why NECTIN4 looked like it was everywhere. 🎯
And it matters, because only one compartment predicts anything:
✅ Membranous 2+/3+ vs 0/1+: ORR 55.1% vs 25.5% (p<0.001), mPFS 7.1 vs 2.9 months (HR 0.45), mOS 12.3 vs 6.9 months (HR 0.57).
❌ Cytoplasmic: ORR 49.6% vs 39.5% (p=0.4). No PFS or OS signal.
❌ Bulk NECTIN4 mRNA, which cannot resolve localisation: no association either.
Adding cytoplasmic staining inflates positivity and dilutes prediction. Negativity rate drops from 12% to 3.4%. More positives, less information. 📉
The scoring system 🔬
Four tiers (0, 1+, 2+, 3+) adapted from the ASCO/CAP HER2 gastric algorithm, chosen deliberately because it accounts for incomplete membranous staining, the same framework that carried T-DXd to tumour-agnostic approval.
Blinded interobserver testing, 44 cases, three raters, two with no prior NECTIN4 experience:
📈 Fleiss' κ 0.749 across all four tiers.
📈 Fleiss' κ 0.874 for the clinically relevant 0/1+ vs 2+/3+ cutoff. Almost perfect agreement.
Reproducible, teachable in a short training session, deployable in routine practice.
Genomics on top 🧬
NECTIN4 amplification in 25.1% (45/179). ORR 76.2% vs 36.6%. mPFS 12.2 vs 3.9 months (HR 0.40). mOS 30.1 vs 8.5 months (HR 0.33). At 24 months, 58.8% of amplified patients were alive versus 19.0%.
And IHC prescreens for it: 80% of amplified tumours are 3+, under 5% of 0/1+ tumours carry an amplification. Restricting FISH to 2+/3+ captures 97.8% of amplified cases while sparing 29.1% of patients any molecular testing. ⚡
The integrated three-tier model:
1️⃣ Amplified: ORR 76.2%, mOS 30.1 mo
2️⃣ Non-amplified, membranous high: ORR 42.9%, mOS 8.8 mo
3️⃣ Non-amplified, membranous low: ORR 26.1%, mOS 6.9 mo
Both remained independent in multivariable models. C-index for OS improves from 0.557 to 0.621 when amplification and membranous expression are combined. Neither marker alone does what the two do together.
Where I think this lands 🎯
I do not (!) read this as an argument for testing every patient . With EV+P as first-line standard and few alternatives, a negative result rarely changes what you do today and shouldn't change it right now given the high EVP efficacy.
But that is an argument about the therapeutic landscape, not about the biology. And the landscape is changing fast: HER2 ADCs, TROP2, HER3/EGFR, NECTIN4 radioligands and T-cell engagers. The moment two viable options compete for the same patient, the question stops being "does the target matter" and becomes "which target first."
Notably, unlike the HER2-low paradigm, EV-301 showed an attenuated treatment effect in NECTIN4-low disease, PFS HR around 0.9 with confidence intervals crossing 1 (check out Figure 1 of the paper).
⚠️Prospective validation is running: EVOKE (DRKS00034745).
Immense thanks to @niklas_kluemper and Jonas Saal, to Thomas Büttner, Sebastian Rauch and Fabienne Lange, and to every centre and biobank that contributed. This was a genuinely collaborative effort within the fantastic GUARDIANS and BRIDGE Consortium. 🙏
🔗 doi.org/10.1158/1078-0432.CC…
@Uroweb @AmerUrological @ASCO @PathSoc @OncoAlert @Histo_Journal @andreanecchi @emanuele_crupi @danieleraggi83 @raffcolo @Dr_Aggen @DrRosenbergMSK @h_alahmadie @PGrivasMDPhD @shilpaonc @drenriquegrande @amerseburger @brookmans76 @DrYukselUrun @onkowissen @imedverse @UroDocAsh @urotoday @EUplatinum @JCO_ASCO @CCR_AACR @niklas_kluemper @DrRosenbergMSK @Dr_Aggen @Uromigos @tompowles1 @shilpaonc @PGrivasMDPhD
#Uropathology #urothelial #BladderCancer #NECTIN4 #pathtwitter
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RT @niklas_kluemper: Happy to share our new paper in Clinical Cancer Research on NECTIN4 as a biomarker for enfortumab vedotin in urothelia…
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Ashish M. Kamat, MD, MBBS retweeted
Making sense of efficacy endpoints in #NMIBC trials: Response, durability, and clinical benefit. @UroDocAsh @UTMDAnderson joins @UroCancerMD @VUMChealth examining clinical trial endpoint evolution in NMIBC. Dr. Kamat argues that CR rates in BCG-unresponsive CIS were developed as regulatory rather than clinical definitions, and that landmark event-free survival figures better inform patient counseling. #WatchNow > bit.ly/3ROeAPe
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Ashish M. Kamat, MD, MBBS retweeted
⚡️ pCR rates of 55–57% with perioperative EV + pembrolizumab in MIBC are real. But clinical complete response is not a reliable surrogate for pathologic clearance.
52% of patients with endoscopic cCR still harbor residual tumor at cystectomy. ctDNA misses up to 1 in 5 cases of residual disease.
Bladder preservation is achievable in selected patients — but rigorous prospective validation is still needed before deferring cystectomy.
auanews.net/issues/articles/…
#BladderCancer
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Tyra Biosciences Reports Initial Phase 2 results of SURF302 : Dabogratinib in LG IR NMIBC
prn.to/4gSU4qt
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Ashish M. Kamat, MD, MBBS retweeted
Tremendous work from a team led by @kor_shah @SalvadorjcMD & @ruchi1agarwal, co-first authors on this piece in @JAMANetworkOpen highlighting the regional variations in #bladdercancer trials in the US. Their detailed analysis of regional variations in study availability points to a misalignment between trial access & disease burden. Tagging @IBCG_BladderCA @BladderCancerUS & other groups fighting for access to #clinicaltrials for our patients.
Our study is now published in @JAMANetworkOpen!
We mapped 436 bladder cancer clinical trials across US counties and examined associations with incidence, mortality, & social vulnerability. Among 3,145 US counties, 77.3% had no bladder cancer trials! 🧵⬇️
jamanetwork.com/journals/jam…
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Bladder Preservation After Neoadjuvant Chemotherapy: Stick to the Plan! -
auanews.net/issues/articles/…
@AmerUrological @IBCG_BladderCA @AmyLuckenbaugh @shilpaonc @ARRODRIGUEZMD #BladderCancer
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Ashish M. Kamat, MD, MBBS retweeted
Graphical reconstruction method compares neoadjuvant regimens in cisplatin-ineligible #MIBC. @BrigidaMaiorano @SanRaffaeleMI joins @UroDocAsh @UTMDAnderson to discuss an indirect comparison of EV-303 and PURE-01 trials using Guyot graphical reconstruction of Kaplan-Meier curves in cisplatin-ineligible muscle-invasive #BladderCancer. The provocative analysis questions enfortumab vedotin's contribution to pembrolizumab efficacy. #WatchNow on UroToday > bit.ly/4gTBPl9
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Important change in the 2026 @AmerUrological NMIBC Guidelines: all high-grade Ta tumors are now classified as high-risk.
This reduces a long-standing source of heterogeneity in the intermediate-risk group and should improve risk-appropriate treatment for patients, while creating cleaner, more meaningful populations for clinical trials.
Great to see the evidence translate into practice. @IBCG_BladderCA @UrogerliMD @pjhensley11 @AmirHorowitz @mouwlab @spsutkaMD @shilpaonc @AndreaNecchi @LAUrology_NL @karima_oualla @PGrivasMDPhD @marigfern @SpiessPhilippe @UroCancerMD
Time to revisit something I’ve been saying for years: TaHG bladder cancer is not intermediate risk. The clinical outcomes, molecular biology ... all point in the same direction.
Yet some frameworks allow < 3cm TaHG tumors to be downgraded into “intermediate risk” alongside low-grade disease.
That classification has real consequences for patients:
• undertreatment
• less rigorous surveillance
• in some studies, these patients are even placed on observation as a supposedly appropriate “control arm.”
TaHG is high risk. 🧵 @BladderCancerUS @WorldBladderCan @IBCG_BladderCA
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Ashish M. Kamat, MD, MBBS retweeted
Findings from the bladder burden survey: Patient perspectives on communication, trust, and quality of life in #BladderCancer. Meri-Margaret Deoudes, CFRE @BladderCancerUS joins @UroDocAsh @UTMDAnderson to discuss findings from the Bladder Burden Survey. The survey identified delayed diagnosis in women, patient reluctance to discuss bladder cancer due to stigma, and mental health strain as persistent gaps, consistent with prior BCAN and World Bladder Cancer Patient Coalition surveys. #WatchNow > bit.ly/3QvdXcu @WorldBladderCan
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Ashish M. Kamat, MD, MBBS retweeted
Bladder Burden Survey findings on patient trust, unspoken struggles, and mental health in #BladderCancer. @UroDocAsh @UTMDAnderson joins @zklaassen_md @GACancerCenter to discuss the survey findings, covering data collected from approximately 800 patients across six countries and a matched cohort of urologists. #WatchNow > bit.ly/49JzaWM @BladderCancerUS @WorldBladderCan
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Ashish M. Kamat, MD, MBBS retweeted
More than a diagnosis: Global survey exposes the emotional and physical toll of #BladderCancer treatment. Gina Carithers @PCFnews joins @UroDocAsh @UTMDAnderson reflecting on the Bladder Burden Survey, which included responses from more than 800 patients and 800 urologists, and emphasized that many patients hesitate to share how bladder cancer affects daily life because they do not want to burden their doctors. She encourages clinicians to treat each visit as a personal conversation and highlights @BladderCancerUS and the @WorldBladderCan as key organizations expanding patient resources across languages and cultures. #WatchNow >
bit.ly/4fvAZKz
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