For Your Patients: Weighing the Treatment Possibilities for Non-Muscle-Invasive Bladder Cancer

— One method remains standard, but options are expanding

Illustration of 5 circles with different treatment options over over a bladder with urothelial cancer

You've been diagnosed with bladder cancer that has not invaded the muscle layer -- i.e., non-muscle invasive bladder cancer (NMIBC), also called superficial bladder cancer. Although the cure rate with removal of the bladder with radical cystectomy for NMIBC is almost 100%, many patients are not eligible for or decline to have the surgery. The intention of treatment in this situation is to prevent disease progression or recurrence, and to "cure" the cancer without increasing the toxicities with overtreatment.

To accomplish these goals, treatment usually starts with cystoscopy, during which an instrument is inserted into the urethra to examine the bladder to remove the tumor -- a procedure called transurethral resection of bladder tumor (TURBT). The risk of recurrence will then be categorized as low, intermediate, or high based on factors such as the patient's age and the characteristics of the tumor as determined by the pathologist.

Patients determined to have low-risk disease may be advised to undergo a single dose of intravesical (within the bladder) chemotherapy at the time of the initial TURBT.

However, up to 50% of patients are at risk of a recurrence within 12 months of TURBT. For these patients, classified as intermediate-risk or high-risk, radical cystectomy will be offered, but if the patient declines, further treatment after TURBT will be recommended -- typically a 6-week course of intravesical immunotherapy or chemotherapy.

Bacillus Calmette-Guerin (BCG) is the most frequently used intravesical immunotherapy for this purpose. BCG is a weak form of the tuberculosis bacteria, which stimulates the immune system to attack cancer cells. The initial BCG treatment is inserted via a thin flexible catheter passed through the urethra, administered as a liquid inserted directly into the bladder, sparing side effects outside of the bladder.

The BCG instilled into the bladder remains in the bladder for up to 2 hours, and after the patient returns home the catheter may sometimes need to remain in place for a few days to drain urine. During the course of induction BCG, once weekly treatments are administered for up to 6 weeks.

Additional series of BCG treatments, called maintenance BCG, may continue for as long as a year in patients at intermediate risk of recurrence, and for up to 3 years in those at high risk.

A total of 30-40% of patients, however, do not respond to BCG. For such patients, an option is sequential intravesical chemotherapy with gemcitabine and docetaxel, or single agent docetaxel or valrubicin, given once a week for 6 weeks followed by up to 2 years of maintenance therapy. With intravesical chemotherapy, more than 80% of patients remain alive without their cancer recurring at 2 years.

Another option for patients with high-risk BCG-unresponsive NMIBC is intravenous pembrolizumab, which is a form of systemic immunotherapy. Also showing promise is a novel intravesical strategy combining intravesical BCG with ALT-803 (N-803) in patients with NMIBC that is unresponsive to BCG.

In December 2022, the Food and Drug Administration approved the first gene therapy -- nadofaragene firadenovec (Adstiladrin) -- for treatment of adults with high-risk, BCG-unresponsive NMIBC. In a study known as CS-003, about half of the patients who received intravesical therapy had a complete response, and half of these remained in complete remission for at least 1 year.

Read previous installments in this series:

For Your Patients: Urothelial Cancer 101

For Your Patients: Staging Urothelial Cancer

"Medical Journeys" is a set of clinical resources reviewed by physicians, meant for the medical team as well as the patients they serve. Each episode of this journey through a disease state contains both a physician guide and a downloadable/printable patient resource. "Medical Journeys" chart a path each step of the way for physicians and patients and provide continual resources and support, as the caregiver team navigates the course of a disease.