Markus Eckstein

Thanks for picking our study up! A pleasure !!! @urotoday @OncoAlert

🧬🔬 MOSAIC is out in Genome Medicine! The Multi-Omics Spatial Atlas in Cancer: >2,700 tumor samples across ≥10 tumor types, generated in standardized labs at 5 founding partners (CHUV, Charité, UK Erlangen, Gustave Roussy, Pitt) together with Owkin (@OwkinScience) 📦 6 modalities from ONE FFPE block:
• H&E whole slide images
• Visium CytAssist spatial transcriptomics
• snRNA-seq (Chromium Flex)
• Bulk RNA-seq
• Whole exome sequencing
• Curated clinical data 🔓 MOSAIC Window, the first open release: 60 patients with bladder cancer, ovarian cancer, GBM, DLBCL and mesothelioma, available via EGA. Key findings:
🧩 Most tumors harbor ≥2 genomically, spatially and transcriptionally distinct malignant subsets (pan-cancer median 3, GBM median 6) 
🫧 Bladder cancer shows the highest inter-patient heterogeneity of all indications 
🔗 Tumor cell signaling tracks with its neighborhood: TGF-β ↔ fibroblasts, VEGF and JAK-STAT ↔ macrophages 
🧬 Copy number profiles do not always dictate transcriptomic state, pointing to passenger alterations 4 case studies with a therapeutic angle:
🎯 Mesothelioma: an inflamed, MET-active niche with high anti-PD-1 signature next to an immune-cold niche in the same tumor
🎯 Bladder: squamous/keratinizing vs. proliferative subsets independent of CN background; CEACAM5/6 confined to nest cores, relevant for ADC targeting
🎯 Ovarian: HRD signature restricted to one subset, suggesting heterogeneous PARPi sensitivity 💡 Bulk profiling averages out exactly the niches that may decide treatment response. Proud that Erlangen Pathology is a founding partner. Thanks to all patients, the Owkin team and every co-author 🙏. This is just the first step on a great journey with MOSAIC #PathTwitter #SpatialTranscriptomics #SingleCell #Multiomics #DigitalPathology #AIinPathology #PrecisionOncology #TumorHeterogeneity #BladderCancer #OpenData 📄 doi.org/10.1186/s13073-026-0…

An introduction to MIBC (and mUC) in graphical narrative abstract. Please note: there are more subtype/variant histologies (there will be a separate thread in this).

🔬 Great summary by @niklas_kluemper on KEYNOTE-905/EV-303 at #ESMO2026. Let me add the pathology angle, because his key question is ours to answer. The ad hoc analysis, 255 concurrently randomised, cisplatin-ineligible: 📊 2-yr EFS 41% / 56% / 76% (cystectomy / pembro / EV+P)
🔬 pCR 10% / 25% / 59%
📉 EFS HR 0.71 (0.47–1.07) for pembro, 0.40 (0.25–0.65) for EV+P
⚠️ Grade ≥3 TEAEs 42% / 70% / 69% Two things I keep coming back to 🧠 1️⃣ The toxicity numbers look reassuring and are not. 70 vs 69% grade ≥3 says EV adds no extra severe events, but a single rate collapses two very different profiles. Neuropathy, skin and metabolic toxicity in a curative-intent setting are not interchangeable with immune-related events, and they persist in survivors. Equal rates, unequal consequences. 2️⃣ 41% of patients on EV+P still have residual disease. We will not find them just with a IHC cutoff. Membranous Nectin-4, read on the membrane only, together with histological subtype and divergent squamous differentiation, is the most informative combination we already have and routinely leave unmeasured. And a pathology point that follows directly: once pCR carries this much weight, ypT0N0 at cystectomy becomes a high-stakes diagnosis. Thus, Sampling protocols and regression assessment need to be standardised and centrally reviewed, not left to local practice. 🎯 Also worth stating plainly: this is an ad hoc comparison, not a powered head-to-head. Pembro alone did not separate from surgery here (CI crosses 1). Interpret the three-arm ranking accordingly. Looking forward to Sunday's symposium. 🎤 ESMO 2026 | KEYNOTE-905/EV-303 | Abstract 4733O @niklas_kluemper @OncoAlert @DrChoueiri @tompowles1 @apolo_andrea @neerajaiims @montypal @Silke_Gillessen @AOmlin @brian_rini @PGrivasMDPhD @TiansterZhang @amerseburger @DrDanielHeng @HHammersMD @scocmem @AndreaNecchi @AmandaNizamMD @drenriquegrande @nataliagandur @AlbigesL @cdanicas @declangmurphy @seanmmcbride @shilpaonc @DrRanaMcKay @scserendipity1 @DrYukselUrun @ravikanesvaran @BraunMDPhD @EfstathiouEleni @mzugman @crisbergerot #Uropathology #BladderCancer #blcsm #pathtwitter

🚨 Perioperative immunotherapy in MIBC at #ESMO2026. Three phase III trials, three different answers, and one uncomfortable lesson for those of us who report pCR. 🔬 📊 NIAGARA (durvalumab + GC, n=1,063): pCR 37.3%, EFS HR 0.68 (0.56–0.82), OS HR 0.75 (0.59–0.95) ✅ 
📊 KEYNOTE-866 (pembrolizumab + GC, n=907): pCR 44.4%, EFS HR 0.88 (0.71–1.10), OS HR 1.00 (0.76–1.27) ❌ 
📊 CA017-078 (nivolumab + GC, n=653): pCR 39.1%, EFS HR 0.94 (0.71–1.25), OS HR 0.88 (0.64–1.21), OS immature ❌ Cross-trial, not head to head. Populations, schedules, follow-up (34 to 55 months) and statistical design all differ, so the ranking is exploratory. But look at the direction. The trial with the highest pCR returned an OS hazard ratio of exactly 1.00. 🧠 Three points from the pathology side: 1️⃣ pCR is a response marker, not a surrogate. Comparable absolute pCR gains of roughly 9 to 10 points across all three, divergent survival. If pCR tracked cure, that pattern should not be possible. pCR remains elusive at least for standard chemotherapy plus IO. 2. And pCR itself is not standardised across trials. ypT0N0 depends on sampling protocol, block numbers, regression assessment and whether review is central or local. The NIAGARA figure quoted here comes from a reanalysis, which tells you the endpoint moved on re-review. A 9-point difference is not comfortably above that measurement noise. Also worth noting: NIAGARA and KEYNOTE-866 both gave adjuvant IO, CA017-078 did not. So adjuvant continuation alone does not explain the split either. We genuinely do not know why these diverged. 🎯 Which is the real message. We are comparing trials on an endpoint we produce, that is not validated, not standardised, and not stratified by biology. Fixing that is a pathology job, and it is overdue. We need that now more than ever with neoadjuvant systemic phase becoming SOC. @OncoAlert @DrChoueiri @tompowles1 @apolo_andrea @neerajaiims @montypal @Silke_Gillessen @AOmlin @brian_rini @PGrivasMDPhD @TiansterZhang @amerseburger @DrDanielHeng @HHammersMD @scocmem @AndreaNecchi @AmandaNizamMD @drenriquegrande @nataliagandur @AlbigesL @cdanicas @declangmurphy @seanmmcbride @shilpaonc @DrRanaMcKay @scserendipity1 @DrYukselUrun @ravikanesvaran @BraunMDPhD @EfstathiouEleni @mzugman @crisbergerot #Uropathology #BladderCancer #blcsm #MIBC #pathtwitter Great summary below from Niklas Klümper.

What a great honor @niklas_kluemper ! Well deserved and you did a great job. Your dedication about urooncology brought you there and will even bring you far further - carry on my friend it is a pleasure and just fun working with you and trying to shape the UC sphere for the best of our patients!

Really encouraging data. And trop2 is ubiquitous except for NEC and sarcomatoid. Exciting data for challenge!