Updated Standard Practice for Managing Patients with Non-Muscle-Invasive Bladder Cancer

The management of non-muscle invasive bladder cancer (NMIBC) starts with the resection of all visible disease, with a focus on the existing standard of care, intravesical Bacillus Calmette–Guérin (BCG), for patients with this disease, according to a presentation at the 2021 New York GU 14th Annual Interdisciplinary Prostate Cancer Congress®.¹

More, for patients with high-grade disease, intravesical BCG therapy should be considered, while only follow-up cystoscopy is necessary for patients with low-grade, low-volume disease.

“Non-muscle invasive bladder cancer management is something commonly encountered by urologists,” Leonard G. Gomella, MD, FACS, chairman of the Department of Urology at the Sidney Kimmel Cancer Center, explained in his presentation. “Initial management [is to] resect all visible disease and think about enhanced cystoscopy as a way to complete that process. If [the disease is] high-grade, consider intravesical BCG therapy; [and with] low-volume, just usually do follow-up cystoscopy.”

The standard approach utilized by most care providers for BCG intravesical immunotherapy is known as the SWOG protocol, in which patients receive an initial 6-weekly induction dose, followed by 3 weekly doses at 3 months and every 6 months following initial treatment for up to 2 or 3 years.

Along with a robust response, BCG therapy is typically well tolerated. Some common adverse events associated with BCG treatment include fever, hematuria, and granulomatous prostatitis.

While BCG is the current standard of care for NMIBC, BCG failures do exist. Specifically, recurrence and progression can happen with treatment via BCG, with 1- and 5-year recurrence rates of 15% to 61% and 31%to 78%, respectively. As for progression, the 1- and 5-year rates are up to 17% and up to 45%, respectively. These existing data strengthen the need for additional therapeutic options for patients with this disease.²

“There’s no question that BCG is probably the best-known immuno-oncology agent,” explained Gomella. “In reality, we’ve been using BCG for bladder cancer certainly since the FDA approval way back in 1990, and it’s really become the standard of care for non-muscle invasive bladder cancer.”

Among patients who are eligible for BCG, data suggests up to 40% may not respond to treatment or will become refractory to BCG. For high-risk patients who fit this description, Gomella explains that radical cystectomy should be considered as the first option. If patients are unwilling to undergo cystectomy or prefer another therapy, Gomella continued to say that intravesical chemotherapy, among other therapies, represent an option although noting its limited success.

For intravesical chemotherapy, monotherapy treatment is less efficacious than BCG, with paclitaxel, docetaxel, doxorubicin, epirubicin, and valrubicin (Valstar) among the drugs utilized in this treatment. Gomella noted that valrubicin is the only drug that has received FDA approval for this indication.

More, systemic pembrolizumab (Keytruda) to treat patients with BCG-refractory bladder cancer was recently approved by the FDA in response to data from the phase 2 KEYNOTE-057 study (NCT02625961).^3,4

The median duration of response was 12.7 months (range, 0.0+ to 20.5+ months), with 75% of patients experiencing a complete response duration of 6 or more months and 53% of patients showing a complete response duration of 9 or more months.

“If you have a high-grade BCG failure, valrubicin and systemic pembrolizumab currently are the FDA approved salvage medications,” concluded Gomella. “Again, cystectomy should always be considered and at least presented to the patient.”

References:

1. Gomella LG. Management of Non–Muscle-Invasive Bladder Cancer. Presented at: 14th Annual New York GU Congress. March 12-13, 2021.

2. Chang SS, Boorjian SA, Chou R et al. Diagnosis and treatment of non-muscle invasive bladder cancer: AUA/SUO guideline. J Urol. 2016;196(4):1021-1029. doi: 10.1016/j.juro.2016.06.049

3. FDA approves pembrolizumab for BCG-unresponsive, high-risk non-muscle invasive bladder cancer. FDA. January 8, 2020. Accessed March 12, 2021. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pembrolizumab-bcg-unresponsive-high-risk-non-muscle-invasive-bladder-cancer

4. Balar AV, Kamat AM, Kulkarni GS, et al. Pembrolizumab (pembro) for the treatment of patients with Bacillus Calmette-Guérin (BCG) unresponsive, high-risk (HR) non–muscle-invasive bladder cancer (NMIBC): Over two years follow-up of KEYNOTE-057. J Clin Oncol. 2020;38(suppl 15):5041. doi: 10.1200/JCO.2020.38.15_suppl.5041