Dr Sfakianos on Addressing Unmet Needs With Intravesical Mitomycin in Recurrent, Low-Grade, Intermediate-Risk NMIBC

“The biggest unmet need [has been] the [ability] to treat patients with low-grade and intermediate-risk bladder cancer. This is a disease with a high recurrence rate, and it is very cumbersome for patients because of that recurrence rate.”

John P. Sfakianos, MD, an associate professor of urology and urologic oncology at the Icahn School of Medicine at Mount Sinai, discussed the rationale for evaluating mitomycin intravesical solution (Zusduri; formerly UGN-102) for the treatment of patients with recurrent, low-grade, intermediate-risk non–muscle-invasive bladder cancer (NMIBC) and the mechanism of action of the FDA-approved agent.

The capability to effectively treat patients with low-grade and intermediate-risk bladder cancer has historically represented a significant unmet need, Sfakianos began. Of note, the recurrence rate of the disease is high, which can be a difficult experience for patients, he explained. Historically, surgery was a mainstay, in which patients would have their tumors resected and undergo anesthesia several times, he stated. Therefore, the rationale of the phase 3 ENVISION trial (NCT05243550) was to identify a nonoperative approach for the treatment of patients with low-grade, intermediate-risk bladder cancer, he asserted. He also noted that data from the phase 3 ATLAS trial (NCT04688931) demonstrated that there was efficacy using a chemo-ablative approach in the respective disease state.

Of note, the mitomycin intravesical solution is a thermal, reversible hydrogel that is instilled with mitomycin, Sfakianos continued. Once the thermal gel is located in the bladder, it slowly disintegrates and disperses the mitomycin, and therefore has a larger contact time with the tumors along with the chemotherapy agent, he explained. Previously, viscous mitomycin was evaluated; however, the length of contact time varies in patients, he emphasized.

Notably, in May 2025, the FDA’s Oncologic Drugs Advisory Committee (ODAC) voted 5 to 4 against the risk:benefit profile of mitomycin intravesical solution for the treatment of patients with recurrent, low-grade, intermediate-risk NMIBC. However, in June 2025, the FDA approved mitomycin intravesical solution for the respective patient population, despite the ODAC decision.