How to prioritize among novel treatment options in NMIBC

In this video, recorded at the 2025 Society of Urologic Oncology Annual Meeting in Phoenix, Arizona, Siamak Daneshmand, MD, a professor of urology (clinical scholar) and director of Clinical Research at Keck School of Medicine of the University of Southern California, Los Angeles, discusses the rapidly expanding treatment landscape for patients with BCG-unresponsive non–muscle invasive bladder cancer (NMIBC). He notes that clinicians now have several therapeutic options, including systemic pembrolizumab (Keytruda), agents such as nadofaragene firadenovec (Adstiladrin), IL-15 superagonists, and other novel therapies. Each treatment comes with its own strengths and limitations, but evidence is still emerging regarding how best to match individual patients to specific agents.

Daneshmand emphasizes that, at present, optimal patient selection remains unclear because resistance mechanisms and predictive biomarkers are not yet well understood. As a result, clinicians must rely on practical considerations when choosing therapy. These include treatment availability, patient tolerance, logistical issues such as travel distance and required frequency of visits, and financial factors like insurance coverage. Until more data are available, he describes the decision-making process as somewhat of a “dealer’s choice,” with clinicians grateful to have multiple options they can tailor to patient needs.

Sequencing therapies after failure of an initial agent is another unresolved challenge. Daneshmand states that the field lacks data to guide which therapy should follow another or whether resistance to one predicts lack of response to others. Current scientific investigations into resistance patterns have yet to yield actionable insights.

Looking ahead, Daneshmand expresses optimism about continued progress in NMIBC. Numerous ongoing clinical trials are evaluating new agents and combination regimens. Although many therapies achieve strong initial complete response rates in the first 1 to 2 years—often in the 70% to 80% range—durability remains an issue, with 1-year response rates commonly dropping to 40% to 50%. Daneshmand said he believes combination strategies may help sustain responses and further improve outcomes. Overall, he sees a promising future as the field works toward more durable, personalized therapies for high-risk NMIBC.