🚨 DAY 3 | #GUARDSymposium2026 🇪🇸 🌌 When does “advanced” urothelial cancer really begin? 🎙️ Dr. @tompowles1 🇬🇧 | Barts Cancer Institute 📡 @OncoAlert × @GuardConsortium A fascinating way to start the advanced bladder cancer session. Powles used Andromeda to challenge a very simple assumption: What we can see is not necessarily all the disease that is already there. Radiology defines visible disease. But micrometastatic disease may already exist below the threshold of imaging — and ctDNA may allow us to detect that biology earlier. This raises a provocative question: 👉 Does “advanced disease” begin when metastases become radiologically visible — or when molecular evidence tells us the disease has already escaped? Post-surgery ctDNA levels clearly stratify prognosis, and dynamic changes can be informative very early: 🔹 clearance → better outcomes 🔹 falling ctDNA → intermediate risk 🔹 persistent or rising ctDNA → substantially worse prognosis So perhaps the boundary between localized and advanced disease is becoming less anatomical and more biological. And then came the historical perspective. A few years ago, first-line trials were still asking whether adding checkpoint inhibition to platinum chemotherapy could meaningfully move the needle. Now, EV-302/KEYNOTE-A39 has completely changed the first-line landscape. At ~3.5 years of follow-up, EV + pembrolizumab continues to show durable benefit, but one detail is particularly striking: complete responses can deepen over time. Among patients achieving CR with EV + pembrolizumab, many did not start with CR. They first achieved a partial response — and then converted to CR later. And importantly, patients whose response deepened from PR → CR had similar 3.5-year survival to the overall CR population: 82.4% vs 83.6%. That changes how we think about response assessment. 🎯 My takeaway: We may need to rethink two traditional boundaries in urothelial cancer: 1️⃣ When does advanced disease really begin? Perhaps before radiology can see it. 2️⃣ When is the final depth of response really known? Perhaps much later than the first scan suggests. From ctDNA-detected molecular disease to delayed conversion from PR to CR, the common theme is the same: biology evolves continuously — our clinical categories are the ones that are discrete. And that may be one of the most important lessons as treatment becomes more effective. @OncoAlert @GuardConsortium @cdanicas @tompowles1 @DrRosenbergMSK @AndreaNecchi @urbano_anido @drenriquegrande @mjuanfi81 @tonivilaseca @MarioHArroyo @DrJaVallejo @dralvaropinto @Ecastromarcos @OncBrothers #BladderCancer #UrothelialCancer #ctDNA #GUOncology

🚨 DAY 3 #GUARDSymposium2026 🇪🇸 PART 3 🟣 Who gets EV + pembrolizumab today — and who might get it tomorrow? 🎙️ @tompowles1 🇬🇧 | Barts Cancer Institute 📡 @OncoAlert × @GuardConsortium Perhaps the most provocative part of the discussion was what comes after establishing EV + pembrolizumab as a highly active first-line strategy. The next questions are no longer only about efficacy. They are about duration, de-escalation, biomarkers and moving treatment into earlier disease. Real patients illustrate why this is difficult: 🔹 prolonged benefit can coexist with cumulative symptomatic toxicity 🔹 treatment may need to be interrupted or one component discontinued 🔹 ctDNA can change before conventional clinical progression 🔹 even patients achieving pCR and ctDNA clearance may ultimately relapse So how should we use all that information? 👉 Can ctDNA help determine when treatment can safely stop? 👉 Can it identify molecular relapse before imaging? 👉 When toxicity forces EV discontinuation, should pembrolizumab continue? 👉 Can EV + P be successfully reintroduced? 👉 And should ADC–ICI combinations move into MIBC and bladder-preservation strategies? Trials exploring approaches such as sac-TMT + pembrolizumab with trimodality therapy are already pushing this concept into earlier-stage disease. And that creates an important shift: The same drugs that transformed metastatic disease may eventually force us to rethink treatment goals in localized disease. 🎯 My takeaway: the future of ADC + immunotherapy in urothelial cancer may be less about adding more treatment and more about learning who needs what, for how long, and at which disease stage. The hardest question may no longer be: “Does EV + pembrolizumab work?” but rather: “How do we personalize its use once it works?” @OncoAlert @GuardConsortium @cdanicas @tompowles1 @DrRosenbergMSK @AndreaNecchi @urbano_anido @mjuanfi81 @drenriquegrande @tonivilaseca @MarioHArroyo @DrJaVallejo @dralvaropinto @Ecastromarcos @OncBrothers #BladderCancer #UrothelialCancer #ctDNA #GUOncology

✨️ DAY 3 #GUARDSymposium2026 🇪🇸 One of the most clinically relevant questions in localized #BladderCancer right now: Are we finally ready to use ctDNA not just to predict relapse, but to guide what we do next? Dr. Sara Coca Membribes 🇬🇧 reviewed the biomarker landscape shaping therapy in urothelial cancer: 🧬 DNA alterations 🎯 FGFR3 🔬 ADC targets such as HER2 and Nectin-4 🛡️ PD-L1 and immune signatures But for me, the most important story is ctDNA. Data from IMvigor010/011 and NIAGARA reinforce that ctDNA can: 🔹 identify molecular residual disease 🔹 anticipate relapse before it becomes radiographically visible 🔹 refine postoperative risk 🔹 potentially help select patients for adjuvant escalation 🔹 and, perhaps just as importantly, spare some patients unnecessary treatment The next step is even more exciting: combining ctDNA + utDNA to support response-adapted bladder-preservation strategies. 🎯 My takeaway: precision oncology becomes truly meaningful when a biomarker changes a decision. The tumor does not need to relapse visibly first. Sometimes the molecular signal comes months earlier — and the challenge is knowing when we are ready to act on it. @Uro_Oncologist @RodriguezFaba @DrFelixGuerrero @cdanicas @drenriquegrande @DrJaVallejo @Maroto5Pablo @AnaPlatabello1 @AndreaNecchi @GuardConsortium #ctDNA #MRD #UrothelialCancer #PrecisionOncology #GUOncology

🚨 DAY 3 #GUARDSymposium2026 🇪🇸 PART 2 🟣 EV + pembrolizumab: responses can deepen with time — and toxicity management matters 🎙️ Dr. Urbano Anido 🇪🇸 📡 @OncoAlert × @GuardConsortium This second part of the case highlighted something increasingly relevant in advanced #UrothelialCancer: an early partial response may not be the final depth of response. With longer follow-up from EV-302/KEYNOTE-A39: 🔹 ORR 67.5% with EV + pembrolizumab 🔹 CR 30.4% vs 14.5% with chemotherapy 🔹 Among patients achieving CR with EV + P, ~2/3 initially had a partial response before converting to CR 🔹 Median time to CR was 4.3 months overall and 6.6 months among those converting from PR to CR And durability remains striking: ➡️ median OS 33.6 vs 15.9 months ➡️ HR 0.53 ➡️ 44% alive at 3.5 years vs 24.6% with chemotherapy But longer treatment also means a different clinical challenge: how do we preserve benefit without allowing cumulative toxicity to compromise the patient? In the presented case, EV dose was reduced after emerging neuropathy, while treatment continued. The longer-term safety data are reassuring in one respect: prolonged exposure did not appear to produce a major increase in grade ≥3 toxicity overall. However, peripheral sensory neuropathy remains the toxicity that increasingly matters with time, making dose interruption and reduction part of treatment optimization, not necessarily treatment failure. 🎯 My takeaway: with EV + pembrolizumab, we may need to think differently about response kinetics. A patient with an early PR may still deepen the response months later, while careful dose modification can help preserve treatment exposure. The challenge is therefore not only to achieve response — but to sustain it long enough, and safely enough, for its full depth to emerge. And one caveat: long-duration treatment analyses are inherently enriched for patients who were benefiting and tolerating therapy, so they should not be interpreted as randomized comparisons of treatment duration. @OncoAlert @GuardConsortium @cdanicas @urbano_anido @tompowles1 @AndreaNecchi @DrRosenbergMSK @mjuanfi81 @drenriquegrande @tonivilaseca @MarioHArroyo @DrJaVallejo @dralvaropinto @Ecastromarcos @OncBrothers #BladderCancer #UrothelialCancer #GUOncology

✨️ DÍA 1 #GUARDSymposium2026 🇪🇸 Una pregunta que cada vez pesa más en #ProstateCancer de alto riesgo: ¿La SBRT es simplemente una forma más corta de radioterapia — o puede convertirse en una estrategia realmente más personalizada? La Dra. @GiuliaMarvaso84 🇮🇹 revisó el papel creciente de la SBRT en este escenario, incluyendo: ☢️ ultra-hipofraccionamiento 🎯 escalada focal de dosis 🧬 irradiación nodal pélvica 💊 integración con ADT e intensificación sistémica Lo más interesante no es solo reducir el número de fracciones. Es la posibilidad de combinar precisión de dosis, riesgo biológico y tratamiento sistémico de una forma más adaptada al paciente. 📊 Los datos iniciales son prometedores en términos de viabilidad y control de enfermedad, pero todavía necesitamos ensayos aleatorizados y mayor madurez de seguimiento. 🎯 Mi takeaway: el futuro de la SBRT en enfermedad de alto riesgo probablemente dependerá menos de “dar menos fracciones” y más de definir a quién tratar, qué volumen irradiar, dónde intensificar y cómo integrar la terapia sistémica. Ahí es donde la radioterapia de precisión empieza a ser realmente personalizada. 👥 ¿Creen que la SBRT está lista para ampliar su lugar en el alto riesgo o todavía debemos esperar más evidencia aleatorizada? @GiuliaMarvaso84 @fcounago @F_lopez_campo @NicosiaMd @DrIacovelli @Dolmos77 @dralvaropinto @nachoduranm @BerUrologia @GuardConsortium #GUOncology #SBRT #Radioterapia #HighRiskProstateCancer #PrecisionOncology

🚨 DAY 2 | #GUARDSymposium2026 One of the clearest signs that radioligand therapy is maturing is that the question is no longer “Does it work?” — but “How do we use it best?” Dr. David Kersting 🇩🇪 reviewed the evolution of PSMA-targeted RLT in #mCRPC, from TheraP and VISION to PSMAfore, SPLASH and ENZA-P. ☢️ The field is now moving toward: 🔹 earlier treatment lines 🔹 smarter sequencing 🔹 combination strategies 🔹 new targets such as ACP3 and GRPR 🔹 alpha emitters For me, the implementation challenge is becoming as important as the efficacy data. We now need to define: • who should receive RLT earlier • how PSMA imaging should guide selection • when to combine vs sequence • how to preserve marrow reserve and future options • how to approach PSMA-low or heterogeneous disease 🎯 My takeaway: the next generation of theranostics will not be about adding more radioligand therapy — it will be about matching the right radioligand strategy to the right biology, at the right moment. @DrJaVallejo @dralvaropinto @Maroto5Pablo @Uro_Oncologist @Dav_Lorente @Prof_Nick_James @g_develasco @tonivilaseca @DrFelixGuerrero @GuardConsortium #ProstateCancer #PSMA #RadioligandTherapy #Theranostics #GUOncology