Discussing Challenging Cases in NMIBC
Key Points
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Bacillus Calmette-Guérin (BCG) is a mainstay therapy for non-muscle invasive bladder cancer (NMIBC), but more effective options are needed.
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The POTOMAC and CREST trials explored combinations of BCG and immunotherapy agents in the high-risk NMIBC population.
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There is an unmet need for additional treatments in BCG-unresponsive NMIBC, though novel agents and novel drug delivery mechanisms are being explored.
NMIBC Case Studies
Cohosts of the Oncology Brothers podcast, Rahul Gosain, MD, MBA, of Wilmot Cancer Institute, and Rohit Gosain, MD, of Roswell Park Comprehensive Cancer Center, joined medical oncologist Shilpa Gupta, MD, of Cleveland Clinic, and urologist Joshua Meeks, MD, PhD, of Northwestern University, to discuss challenging cases in NMIBC.
Case 1: Considering BCG Plus Immunotherapy
The first case described a high-risk 71-year-old man presenting with hematuria, mild anemia, and an unremarkable comprehensive metabolic panel. The patient was a former smoker and had a history of diabetes mellitus type II, hypertension, and hyperlipidemia. Upon workup and transurethral resection of the tumor, the patient was staged with a grade 3 multifocal papillary TaHG tumor with no muscle involvement.
This case represents a standard high-risk patient with NMIBC based on the high-grade, multifocal tumor. This patient population faces a low risk of progression to muscle-invasive disease, but a high risk of recurrence within 3 years, said Dr. Meeks.
Historically, BCG monotherapy has been used to treat this population. Recently, trials have explored the combination of BCG and immunotherapy agents. The CREST, POTOMAC, and ALBAN trials evaluated BCG combined with sasanlimab, durvalumab, and atezolizumab, respectively. The ALBAN trial was negative, but both CREST and POTOMAC reported a benefit from adding immunotherapy to BCG.
While some subgroups in POTOMAC and CREST showed greater benefit from combination therapy, selecting patients for immunotherapy may ultimately come down to the patient’s goals, said Dr. Meeks. Some motivated patients may opt for the intensified therapy based on the improved event-free survival outcomes despite the risk of increased toxicities. If these regimens see more uptake, greater partnership between urologists and medical oncologists may be necessary to discuss the risk-benefit balance with patients and manage the logistics of systemic immunotherapy, Dr. Gupta added.
Case 2: Treatment Options for BCG-Unresponsive NMIBC
The doctors next considered the case of a 74-year-old woman presenting with ongoing urinary retention. The patient had a history of heavy smoking, osteoarthritis, hypertension, anxiety, and gastroesophageal reflux disease. The NMIBC workup identified a large grade 3 solitary papillary T1HG tumor with carcinoma in situ detected. The patient previously received BCG about 1 year ago, and was not in favor of cystectomy to preserve her bladder.
Data on immunotherapy in BCG-unresponsive patients are sparse, though the ongoing KEYNOTE-676 is evaluating pembrolizumab plus BCG in this population. The only available data on rescue immunotherapy after BCG failure were from KEYNOTE-057, which Dr. Meeks said he did not find compelling enough to consider using pembrolizumab for this case. If the patient had responded to prior BCG and had a sufficiently long disease-free interval before recurrence, rechallenging with BCG would be an option.
Dr. Meeks and Dr. Gupta agreed they would likely pursue other standard treatments for BCG-unresponsive NMIBC. FDA-approved treatments include valrubicin and nadofaragene firadenovec, and gemcitabine plus docetaxel has been used off-label. Clinical trials are also investigating novel agents and novel drug delivery systems.