Dr Galsky on Systemic Therapy Advances in Muscle-Invasive Bladder Cancer

“This is the third major advance with the integration of enfortumab vedotin plus pembrolizumab into the perioperative systemic treatment of MIBC, and arguably the most substantial.”

Matthew Galsky, MD, a professor of medicine (hematology and medical oncology), director of genitourinary medical oncology, codirector of the Center of Excellence for Bladder Cancer, and deputy director at the Mount Sinai Tisch Cancer Center, discussed the progression of systemic therapy in muscle-invasive bladder cancer (MIBC) in light of the July 2026 FDA approval of pembrolizumab (Keytruda) or pembrolizumab and berahyaluronidase alfa-pmph (Keytruda Qlex) in combination with enfortumab vedotin-ejfv (Padcev) as neoadjuvant treatment followed by adjuvant treatment following cystectomy.

The treatment of MIBC has undergone several transformative advances over the past 3 decades, fundamentally changing the role of systemic therapy in addition to surgery, Galsky began. For many years, radical cystectomy remained the standard treatment for localized MIBC, he noted. However, despite complete surgical removal of the bladder, a substantial proportion of patients experienced metastatic recurrence, highlighting the need for therapies capable of eradicating microscopic disease beyond the primary tumor, he added.

The first major breakthrough in the MIBC setting was the introduction of cisplatin-based neoadjuvant chemotherapy, Galsky explained. Landmark studies, including the phase 3 SWOG 8710 trial, demonstrated that administering cisplatin-containing chemotherapy before radical cystectomy improved patient outcomes compared with surgery alone, he said. These findings established neoadjuvant cisplatin-based chemotherapy as the standard perioperative treatment for eligible patients and represented the first significant advance in systemic therapy for MIBC, he said.

Following this milestone, progress in the field remained relatively limited for many years, Galsky said. The next major evolution occurred with the emergence of immune checkpoint inhibitors, he added. Clinical trials evaluating adjuvant immunotherapy after surgery demonstrated that immune checkpoint blockade could reduce the risk of recurrence in high-risk patients, he said. Subsequent studies further advanced the field by incorporating immune checkpoint inhibitors into cisplatin-based neoadjuvant treatment regimens, producing meaningful improvements in pathologic complete response rates and long-term clinical outcomes, he noted. This marked the second major era of progress in perioperative management.

The integration of enfortumab vedotin plus pembrolizumab into perioperative treatment has ushered in what many consider the third and potentially most impactful advancement in MIBC therapy, Galsky said. By combining an antibody-drug conjugate with immune checkpoint blockade, this regimen expands effective systemic treatment beyond traditional platinum-based chemotherapy and offers new options for a broader range of patients, he concluded.