Dr Lotan on Guideline-Supported Treatment Decision-Making for NMIBC

“If you look at guidelines, you need to really recommend cystectomy, which has the highest cure rate for any patient with BCG-unresponsive disease.”

Yair Lotan, MD, a professor of urology, chief of Urologic Oncology, and holder of the Jane and John Juston Distinguished Chair in Urology, in Honor of Claus G. Roehrborn, MD, the University of Texas (UT) Southwestern Harold C. Simmons Comprehensive Cancer Center; as well as the medical director of the Urology Clinic at UT Southwestern and Parkland Health and Hospital System, discussed recommended treatment options for patients with BCG-unresponsive NMIBC.

In patients with BCG-unresponsive NMIBC, current guidelines strongly recommend radical cystectomy, as it offers the highest likelihood of long-term cure, Lotan began. However, decisions surrounding bladder-sparing approaches depend on multiple clinical factors, including tumor stage, histologic features, patient comorbidities, and life expectancy, he cautioned.

Patients with high-grade T1 disease—particularly those with multifocal or high-volume tumors—who are young and have a long life expectancy, are considered at elevated risk of disease progression and metastasis, Lotan explained. Therefore, cystectomy is typically advised for this population, he said. Conversely, older or frail patients, especially those with limited high-grade Ta disease or carcinoma in situ, may be more appropriate candidates for bladder-sparing therapies, he stated. Retrospective and limited prospective data support a relatively low short-term risk of progression in these cases, making 1 or 2 additional intravesical or systemic treatment attempts reasonable, according to Lotan.

Treatment selection is multifactorial, with complete response (CR) rates and toxicity profiles being key considerations, Lotan emphasized. Systemic immunotherapy with pembrolizumab has shown CR rates of approximately 40%, with durable responses in approximately 60% of responders, though the rate of sustained responses by 1 year drops to approximately 20%, he reported. These agents are generally considered for patients unable to tolerate intravesical therapy due to poor bladder capacity, as they avoid direct bladder instillation but carry systemic toxicity, he highlighted.

Although intravesical agents, such as nadofaragene firadenovec (Adstiladrin) and N-803 (Anktiva), have favorable tolerability profiles and are associated with low systemic toxicity, they come at a substantial cost—approximately $60,000 and $230,000, respectively, Lotan noted. Adstiladrin may be more convenient for patients with transportation challenges due to its quarterly dosing schedule, he said. Intravesical gemcitabine and docetaxel, though lacking prospective trial data, are widely used based on retrospective evidence and low cost, he added. Furthermore, clinical trials remain a vital consideration and should be discussed with all eligible patients, as they may offer access to innovative therapies and contribute to future treatment advancements, Lotan concluded.