S3010
Invited Speaker
ESTRO 2026
improved survival in surgical cohorts, they do not address long-term intravesical control without local therapy. Radiotherapy remains the most effective modality for achieving durable local control if decided against radical cystectomy. To date, no randomized data support the omission of local therapy and explicitly RT in favor of systemic therapy alone. Rather than replacement, the emerging paradigm is integration. Radiotherapy is a potent immunomodulator, and its combination with immune checkpoint inhibitors (ICI) and ADCs offers a biologically compelling strategy. The future of bladder preservation may lie in response-adapted approaches, where systemic therapy identifies exceptional responders and prevents metastatic progression, but RT secures local control in those at risk of residual disease. Several ongoing phase I/II trials are exploring optimal combinations of RT with perioperative or concurrent ADC/ICI therapy. The key question is not whether systemic therapy can replace RT—but whether abandoning RT risks local progression. Until prospective evidence demonstrates equivalent local control without irradiation, radiotherapy remains indispensable. The real opportunity lies in redefining bladder preservation through intelligent multimodal integration. References: 1. Powles T, van der Heijden MS, Loriot Y, et al. Perioperative durvalumab plus gemcitabine and cisplatin in muscle-invasive bladder cancer (NIAGARA). N Engl J Med.2024;390(10): 889-902 2. Rosenberg JE, et al. Enfortumab vedotin plus pembrolizumab in previously untreated muscle- invasive bladder cancer (KEYNOTE-B15/EV-304). J Clin Oncol . 2024;42(18_suppl):LBA4503. 3. Balar AV, et al. Pembrolizumab with or without enfortumab vedotin in cisplatin-ineligible muscle- invasive bladder cancer (KEYNOTE-905/EV-303). J Clin Oncol . 2024;42(18_suppl):LBA4502. 4. Necchi A, et al. End points for the next-generation bladder-sparing perioperative trials for patients with muscle-invasive bladder cancer. J Clin Oncol . 2022;40(5):491–498. 5341 Who benefits? Biomarkers to select treatment for bladder cancer Lars Dyrskjøt Department of Clinical Medicine, Aarhus University, Aarhus, Denmark Muscle-invasive bladder cancer (MIBC) is entering an increasingly complex treatment landscape, where perioperative systemic therapy, radical cystectomy and organ-preserving approaches are being developed in parallel. This creates a need for
presentation will focus specifically on innovations by radiation therapists globally on creating comfort for patients. This includes creating courses to empower patients and their care-givers with information on radiation therapy as a treatment modality or using novel methods to prepare patients for specific procedures such as deep-inspiration breath hold. A pragmatic interpretation of 'comfort' such as optimising of positioning and immobilisation methods including open faced mask technology will be discussed as will creating a calming environment in the room where patients receive their treatment. 5340 Rethinking bladder preservation: Can systemic treatment replace radiotherapy? Ursula Vogl Oncology, Oncology Institute of Southern Switzerland, Bellinzona, Switzerland Bladder preservation in muscle-invasive bladder cancer (MIBC) has traditionally relied on trimodality therapy (TMT), combining maximal transurethral resection, radiotherapy (RT), and radiosensitizing chemotherapy. This approach delivers durable local control and long-term survival comparable to radical cystectomy, establishing RT as a cornerstone of organ preservation. However, the rapid evolution of perioperative systemic therapy is challenging this paradigm. The phase III NIAGARA trial, demonstrated that adding perioperative durvalumab to neoadjuvant cisplatin- based chemotherapy significantly improves survival outcomes and pathological response rates (pCR). In parallel, antibody–drug conjugate (ADC)–based strategies are redefining treatment beyond cisplatin eligibility. The phase III EV-303 and the EV-304 trials established perioperative enfortumab vedotin (EV) plus pembrolizumab (pembro) as an effective strategy in cisplatin-ineligible end eligible patients, significantly improving event-free and overall survival (OS) compared with surgery alone. Impressive pCR up to 65% of patients have catalyzed a shift toward systemic therapy–driven bladder preservation. The upcoming phase II EV-209 trial represents a critical step in this evolution, evaluating EV plus pembro as a bladder-sparing strategy pursued in those achieving a clinical complete response (cCR) in MIBC. This raises a provocative question: if systemic therapy can induce deep and potentially durable responses across both cisplatin-fit and -unfit populations, is local treatment and it this thematic discussion RT still required for bladder preservation? Yet, enthusiasm for systemic-only strategies must be tempered. While perioperative trials demonstrate
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