Neoadjuvant therapy for bladder cancer is evolving fast. In this interview, Dr Petros Grivas (Clinical Director, Genitourinary Cancer Program, University of Washington and Fred Hutchinson Cancer Center) shares his insights into the most exciting advances in neoadjuvant therapy for bladder cancer, drawing on the latest readouts from the European Society for Medical Oncology (ESMO) 2025 congress. He discusses how breakthrough data from NIAGARA, KEYNOTE-905/EV-303 and other key trials are redefining standards of care. From combination immunotherapies to biomarker-driven personalization and bladder preservation strategies, Dr Grivas outlines where the field stands – and where it’s heading next.
Q: How would you describe the current landscape of neoadjuvant therapy for bladder cancer?
Things are changing very rapidly in the neoadjuvant management of muscle-invasive bladder cancer, particularly for patients with localized disease. The NIAGARA trial, presented last year, has already shifted the standard of care for cisplatin-eligible patients. The combination of gemcitabine–cisplatin plus durvalumab given neoadjuvantly, followed by radical cystectomy and eight months of adjuvant durvalumab, has become an established approach.
At ESMO25, we saw compelling new data for cisplatin-ineligible patients, using pembrolizumab plus enfortumab vedotin given perioperatively – before and after radical cystectomy. The study reported pathologic complete response rates of 57% overall, and 65% among those who underwent cystectomy, alongside promising event-free and overall survival benefits. Pending regulatory approval, this combination could soon redefine the standard in this population.
We are also awaiting results from KEYNOTE-B15/EV-304, which compares perioperative enfortumab vedotin plus pembrolizumab against neoadjuvant cisplatin-based chemotherapy in localized MIBC. These data will be pivotal in shaping future standards.
Q: What recent advances do you find most promising?
There’s intense activity in biomarker development and combination strategies aimed at increasing cure rates. Beyond improving systemic efficacy, researchers are also exploring bladder preservation – offering select patients a chance to avoid cystectomy when safe and feasible. Currently, this involves concurrent chemoradiation after maximal TURBT, but with more effective systemic therapies, we may one day be able to identify better which patients can be ‘cured’ with systemic therapy alone.
Another very important area is histology subtype/variant bladder cancer, which remains underrepresented in large trials. We recently published an investigator-initiated phase II trial in European Urology (conducted at University of Washington/Fred Hutch Cancer Center) examining accelerated MVAC (with G-CSF) plus pembrolizumab in 17 patients with histology subtypes, achieving an impressive pathologic complete response rate approaching 60%.1 While with a small sample size, these promising data are hypothesis-generating and underscore the need for dedicated trials in this population.
Q: What gives you the most optimism about the future of neoadjuvant therapy, and what challenges remain?
The most encouraging trend is the rising cure rate. The results with pembrolizumab–enfortumab vedotin are particularly exciting, and I believe we’re moving toward higher cure rates with less invasive treatment. Some patients achieving a clinical complete response after neoadjuvant therapy are now opting out of cystectomy – a choice that must be approached carefully, since clinical response doesn’t always equal pathological response. Designing trials to safely expand bladder-sparing approaches will be key to the next phase of progress.
References
- Ruben Raychaudhuri, Ali Raza Khaki, Mary W Redman, et al. Neoadjuvant Pembrolizumab and Accelerated Methotrexate, Vinblastine, Doxorubicin, and Cisplatin in Nonurothelial Histologic Subtypes of Muscle-invasive Bladder Cancer: A Phase 2 Trial. Eur Urol. 2025;4:S0302-2838(25)00391-4. doi: 10.1016/j.eururo.2025.07.002. Online ahead of print.
Disclosure: Petros Grivas discloses consulting with MSD, Bristol Myers Squibb, AstraZeneca, EMD Serono, Pfizer, Janssen, Roche, Astellas Pharma, Gilead Sciences, Strata Oncology AbbVie, Bicycle Therapeutics, Replimune, Daiichi Sankyo, Foundation Medicine, Eli Lilly, Urogen and Tyra Biosciences. He has received research funding from Bristol-Myers Squibb, MSD, EMD Serono, Gilead Sciences, Acrivon Therapeutics, ALX Oncology and Genentech (paid to the institution).
This content has been developed independently by Touch Medical Media for touchONCOLOGY. It is not affiliated with the European Society for Medical Oncology (ESMO). Views expressed are the speaker’s own and do not necessarily reflect the views of Touch Medical Media.
Cite: Neoadjuvant therapy for muscle-invasive bladder cancer: Where we’re at and where it’s heading. touchONCOLOGY. November 5th, 2025
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