Exploring the Future of Bladder-Sparing Regimens in the MIBC Landscape

At the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting, conversations surrounding bladder preservation in muscle-invasive bladder cancer (MIBC) were a key focus. Eric Miller, MD, an assistant professor of medicine at the Icahn School of Medicine at Mount Sinai and a genitourinary medical oncologist, sat down with CancerNetwork® to highlight the shifting paradigm of selective bladder-sparing strategies moving beyond traditional clinical trial boundaries.

Miller suggested that the evolving treatment landscape emphasizes 2 distinct therapeutic pathways: combining systemic therapies with concurrent radiation—such as adding novel immunotherapies to standard chemoradiotherapy (chemo-RT)—and leveraging systemic therapy alone. Highlighting ongoing research at Mount Sinai, he further outlined institution-led protocols evaluating combinations like gemcitabine, cisplatin, and nivolumab (Opdivo) alongside pembrolizumab (Keytruda) monotherapy and emerging antibody-drug conjugate (ADC) regimens featuring enfortumab vedotin-ejfv (Padcev) plus pembrolizumab.

These prospective approaches point toward a future where treatment sequences—including utilizing systemic combinations followed by chemo-RT for recurrent disease—could significantly reduce reliance on radical cystectomy, offering patients highly effective, organ-preserving alternatives.

CancerNetwork: How do you view the evolution of selective bladder-sparing strategies, particularly those utilizing enfortumab vedotin or pembrolizumab, in terms of their potential to shift the surgical standard of care for MIBC beyond the clinical or trial setting?

Miller: [It is] definitely a huge area of research right now, and there are 2 ways to define bladder sparing. That [includes] systemic therapy with radiation therapy, such as the immunotherapy with chemo-RT trial that I discussed by [Nicholas D. James, PhD, FRCP, MBBS,]. Improving upon the outcomes from chemo-RT is certainly an important strategy in terms of pursuing bladder-sparing strategies. Also, systemic therapy alone is being more talked about as a bladder-sparing strategy.

Our institution has done 2 prior trials, and one that is in progress, that have all been presented, of gemcitabine, cisplatin, and nivolumab in a bladder-sparing protocol, as well as pembrolizumab in a bladder-sparing protocol, and now enfortumab vedotin and pembrolizumab in a bladder-sparing protocol.^2-4 All of these, if we can prove in a prospective fashion that they lead to good outcomes, can lead to a world where bladder-sparing strategies could become much more common, and that it doesn’t have to be one or the other, either. It could be in sequence. For patients who have persistent or recurrent disease after a bladder-sparing strategy seeking to use systemic therapy alone, maybe a chemo-RT strategy could be incorporated afterwards.

Based on the data that we already have of the chemo-RT with immunotherapy and the prior bladder-sparing trials done at Mount Sinai with the gemcitabine, cisplatin, nivolumab, or the pembrolizumab [regimen], I’m optimistic that we’re going to keep seeing more promising data on this.

References

1. James ND, van de Wiel J, De Santis M, et al. Feasibility and safety results from RAD-IO: a multi-stage trial of durvalumab with chemoradiotherapy with 5-fluorouracil and mitomycin C in patients with muscle-invasive bladder cancer. J Clin Oncol. 2026;44(suppl 16):4504. doi:10.1200/JCO.2026.44.16_suppl.4504
2. Galsky MD, Daneshmand S, Izadmehr S, et al. Gemcitabine and cisplatin plus nivolumab as organ-sparing treatment for muscle-invasive bladder cancer: a phase 2 trial. Nat Med. 2023;29(11):2825-2834. doi:10.1038/s41591-023-02568-1
3. Anker JF, King J, Tripathi A, et al. Phase 2 trial of pembrolizumab (P) with response-guided bladder-sparing in patients with muscle-invasive bladder cancer (MIBC; HCRN GU 20-444). J Clin Oncol. 2026;44(suppl 7):737. doi: 10.1200/JCO.2026.44.7_suppl.737
4. Miller EJ, Salous T, Plimack ER, et al. HCRN GU22-598: phase 2 trial of enfortumab vedotin plus pembrolizumab with selective bladder sparing for treatment of muscle-invasive urothelial cancer of the bladder. J Clin Oncol. 2026;44(suppl 7):TPS891. doi:10.1200/JCO.2026.44.7_suppl.TPS891