BCG-Unresponsive NMIBC Management Begins to Shift Away From Bladder Removal

Yair Lotan, MD

When treating patients with Bacillus Calmette–Guérin (BCG)–unresponsive non-muscle invasive bladder cancer (NMIBC), Yair Lotan, MD, cites bladder removal as the best curative option, although this approach is associated with significant long-term adverse effects (AEs). Alternative FDA-approved treatment options for these patients are contingent on patient factors like age, comorbidities, life expectancy, and disease progression risk, he noted.

“Patient goals and desires are the most important factors. It is important for patients to understand the pros and cons of each approach, as there are AEs that can occur with bladder removal or any of these treatments,” Lotan stated in an interview with OncLive®.

In the interview, Lotan discussed the current treatment armamentarium for patients with BCG-unresponsive NMIBC, highlighting both FDA-approved treatment options as well as agents currently under investigation. He also expanded on patient factors that may influence a urologist’s therapeutic decision-making.

Lotan is a professor of urology and chief of Urologic Oncology, as well as the Jane and John Justin Distinguished Chair in Urology at UT Southwestern Medical Center in Dallas, Texas. He also serves as the medical director of the Urology Clinic at UT Southwestern and Parkland Health and Hospital System.

OncLive: Please expand on the current standard of care for patients with BCG-unresponsive NMIBC.

Lotan: The National Comprehensive Cancer Network and American Urological Association guidelines give several [FDA]-approved options [for the treatment of these patients] but also consider commonly available options that are not FDA approved. The first option that should be discussed is bladder removal for patients with noninvasive disease; bladder removal offers the best chance of cure. If a patient has the bladder removed when their cancer is noninvasive, their outcomes are superior to waiting until the cancer becomes invasive. Therefore, there is an opportunity to cure that patient.

However, the consequences of bladder removal are lifelong and can have implications on urinary function—because they have to have a urinary diversion, sexual function, and potentially bowel function. There’s also a fairly high rate of short-term complications that occur with bladder removal. This is a major surgery that usually takes several weeks to months to recover from, and usually the hospital stay is approximately 5 or 6 days, [regardless of] whether [the procedure is] done open or robotically.

What alternative treatment options are available for these patients?

FDA-approved approaches include systemic therapies like pembrolizumab [Keytruda], which is a checkpoint inhibitor, nadofaragene firadenovec-vncg [Adstiladrin], which is a viral therapy that increases production of interferon, and ALT-803 [interleukin-15 complex], which stimulates the immune system. There are also chemotherapy options, which are commonly used but not FDA approved, such as intravesical sequential use of gemcitabine and docetaxel. Clinical trials are also encouraged in the guidelines, if available.

What factors might contribute to making a treatment decision among available therapeutic options for these patients?

Balancing the AEs and the potential efficacy of these treatments relative to the potential risk is the most important aspect of any conversation with a patient. Ultimately, the patient’s going to make the decision. Some of [this choice] has to do with age, comorbidities, surgical risk, and life expectancy. For example, a patient with a long life expectancy [will likely] choose a treatment with a higher cure rate, even if it may be more morbid.

[This decision] also depends on whether patients have signs of disease invasion. Patients with lamina propria invasion of T1 disease have a much higher risk of progression than patients with noninvasive disease confined to the mucosa. Some of [this choice] also has to do with the natural history of their disease.

The final issue is that sometimes patients don’t respond to the initial treatment and still must make a decision [about subsequent treatment] if they recur. Do we want to take out the bladder now, or do we try another treatment? Maybe a patient initially doesn’t want to have their bladder removed but if they try 1, 2, or 3 other potential options, they may concede that they need to have their bladder removed.