Clinical Insights: Evolving Landscapes in MIBC and NMIBC
Key Points
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Perioperative durvalumab with neoadjuvant chemotherapy remains a standard of care option for cisplatin-eligible patients with muscle-invasive bladder cancer (MIBC).
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In non–muscle-invasive bladder cancer (NMIBC), the POTOMAC and CREST trials showed benefit from adding immunotherapy to standard BCG treatment.
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The addition of novel agents to bladder cancer treatment paradigms underscores the need for a multidisciplinary approach to therapy selection and adverse-effect management.
NMIBC and MIBC Data from ASCO GU 2026
At a Clinical Insights discussion coinciding with the 2026 American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO GU 2026), Rahul Gosain, MD, MBA, of Wilmot Cancer Institute, and Rohit Gosain, MD, of Roswell Park Comprehensive Cancer Center—cohosts of the Oncology Brothers podcast—led a panel of urologists and medical oncologists to review evolving treatment paradigms for MIBC and NMIBC.
The panel included urologists Sia Daneshmand, MD, of Keck School of Medicine of USC, and Chad Reichard, MD, of Urology of Indiana, and medical oncologists Matt Galsky, MD, of Mount Sinai, and Shilpa Gupta, MD, of Cleveland Clinic. The panel discussed presentations from the NIAGARA and KEYNOTE-B15 trials in MIBC and the POTOMAC and CREST trials in NMIBC.
Recent Updates to Standard of Care MIBC Therapies
For many years, neoadjuvant cisplatin-based chemotherapy followed by radical cystectomy remained the standard of care for eligible patients with MIBC. In 2025, treatment options expanded with the FDA approval of perioperative durvalumab with neoadjuvant gemcitabine and cisplatin based on the NIAGARA trial. Later that year, the FDA approved enfortumab vedotin plus pembrolizumab (EV-pembrolizumab) for cisplatin-ineligible patients with MIBC based on the KEYNOTE-905 study. Positive data from the NIAGARA and KEYNOTE-B15 regimens support perioperative systemic therapy as an effective treatment option for patients with MIBC, Dr. Galsky said.
Selecting Between Regimens in MIBC
The panel discussed factors that may guide patient selection for either gemcitabine and cisplatin plus durvalumab or EV-pembrolizumab if KEYNOTE-B15 leads to regulatory approval. For cisplatin-ineligible patients, EV-pembrolizumab would be the de facto regimen of choice. For cisplatin-eligible patients, treatment selection may be based on adverse-effect profiles of the NIAGARA and KEYNOTE-B15 regimens.
Medical oncologists are familiar with managing the adverse effects of cisplatin-based chemotherapy, and the NIAGARA data showed that adding durvalumab did not introduce new safety signals. EV-pembrolizumab is associated with pruritus, diarrhea, alopecia, rash, neuropathy, and hyperglycemia. These adverse effects may persist after treatment and require long-term supportive care. KEYNOTE-B15 reported a high rate of neoadjuvant treatment discontinuation, though more data are needed to determine the impact on surgical and adjuvant treatment outcomes, Dr. Gupta said.
In both regimens, the goal is to get patients safely to surgery. To that end, the panel emphasized the importance of partnerships between medical oncologists and urologists. Given the potential for toxicity to affect treatment duration, both specialties should be involved throughout the neoadjuvant treatment period.
ASCO GU 2026 Updates for NMIBC
The standard of care for NMIBC has long been BCG monotherapy. The POTOMAC and CREST trials combined BCG with 1 year of durvalumab and 2 years of sasanlimab, respectively, to improve outcomes. Both trials were positive and may open the door to intensified treatment in patients with NMIBC, pending regulatory approval. More data are needed to guide selection between the two agents, though durvalumab’s shorter duration is a potential benefit.
Implementing these regimens in practice will require careful consideration of potential long-lasting toxicities, Dr. Daneshmand said. Generally, adding durvalumab or sasanlimab to BCG may be most appropriate for patients with high-risk features such as multifocal disease, variant histology, or lymphovascular invasion. BCG alone may still be appropriate for patients with lower risk of progression to systemic disease.
Urology specialists often lead the treatment of NMIBC. However, adding immunotherapy to the standard of care may increase the involvement of medical oncologists, who may be more familiar with managing the associated adverse effects. For example, durvalumab has long been used to treat other cancers. While urologists may still lead patient selection for immunotherapy-intensified treatment, the need for adverse-effect management further reinforces the importance of a multidisciplinary approach, Dr. Rahul Gosain said.