Dr Galsky on the Evolution of the Muscle-Invasive Bladder Cancer Treatment Landscape

“MIBC has traditionally been [managed] with local therapies, including radiation or radical cystectomy. We know that with local therapy alone, there is unfortunately a high risk of metastatic recurrence.”

Matthew Galsky, MD, the director of Genitourinary Medical Oncology, co-director of the Center of Excellence for Bladder Cancer, the deputy director, and a professor of medicine (Hematology and Medical Oncology) at the Mount Sinai Tisch Cancer Center, discussed the evolution of treatment approaches for patients with muscle-invasive bladder cancer (MIBC).

MIBC has historically been managed with local treatment approaches such as radical cystectomy or radiation therapy, Galsky began. However, oncologists have long recognized that local therapy alone is often insufficient because many patients harbor microscopic metastatic disease that is not detected at diagnosis, he added. Due in part to the limitations of clinical staging, approximately 50% of patients treated with local therapy alone ultimately experience metastatic recurrence, highlighting the need for treatment strategies that address both local and systemic disease, he continued.

The development of neoadjuvant cisplatin-based chemotherapy marked one of the first major advances in MIBC management, Galsky noted. Early studies conducted in the 1980s demonstrated that administering cisplatin-based chemotherapy before surgery could reduce tumor burden and increase rates of pathologic complete response, he said. These findings led to phase 3 clinical trials that established neoadjuvant cisplatin-based chemotherapy prior to radical cystectomy as a standard-of-care approach, he said. The goal of this strategy was not only to improve local control but also to eradicate micrometastatic disease and reduce the risk of recurrence, he added.

At the same time, research showed that combining chemotherapy with radiation therapy could provide an effective bladder-preserving alternative for select patients, Galsky explained. This approach offered the possibility of maintaining bladder function while still achieving meaningful disease control, creating a second established treatment paradigm alongside surgery-based management, he added.

Despite these advances, progress in MIBC treatment remained largely stagnant for the next 2 decades, Galsky underscored. Drug development in bladder cancer lagged behind many other malignancies, resulting in relatively few successful systemic therapy innovations, he said. Limited industry investment and research activity contributed to a cycle in which fewer resources were devoted to the disease, slowing therapeutic progress, he said. This landscape began to change with the emergence of immune checkpoint inhibitors, which renewed interest in bladder cancer research and opened the door to a new era of systemic therapy development, ultimately reshaping treatment strategies for patients with MIBC, he concluded.