Matthew Galsky, MD, on how EV/pembrolizumab is redefining the MIBC treatment paradigm

In this interview, Matthew D. Galsky, MD, discusses how the FDA approval of perioperative enfortumab vedotin-ejfv (Padcev) plus pembrolizumab (Keytruda) for patients with muscle-invasive bladder cancer (MIBC) regardless of cisplatin eligibility is reshaping the treatment landscape and raising new questions about the future role of surgery and response-guided approaches. Galsky is a medical oncologist at the Icahn School of Medicine at Mount Sinai and the deputy director of the Mount Sinai Tisch Cancer Center in New York, New York.

Galsky began by explaining how the approval simplifies treatment decision-making for patients with MIBC by providing a single perioperative regimen that can be used regardless of cisplatin eligibility. He noted that cisplatin eligibility criteria were developed largely to standardize clinical trial populations rather than capture the nuances of individual patient care. In clinical practice, determining whether a patient should receive cisplatin-based chemotherapy has often required weighing multiple factors, and the new approval may reduce some of that complexity.

He also emphasized that the approval represents a major shift because it marks the first time a cisplatin-free regimen has demonstrated superiority over cisplatin-based chemotherapy in a head-to-head comparison in the perioperative setting in MIBC. He highlighted the potential benefits of moving away from cisplatin, including avoiding associated toxicities, while noting that the efficacy of enfortumab vedotin plus pembrolizumab has established the regimen as a new standard for eligible patients undergoing treatment for MIBC.

Although the new perioperative paradigm has produced high pathologic response rates, Galsky said radical cystectomy remains a cornerstone of treatment and that response-guided strategies are not yet ready for routine clinical practice. He noted that ongoing trials are evaluating whether patients who achieve favorable responses to systemic therapy may eventually be candidates for bladder-preserving approaches. Future adoption of these strategies will require robust prospective data demonstrating that selected patients can safely avoid surgery while maintaining outcomes comparable to current standards of care.