Rescue BCG for Patients With BCG-Unresponsive Bladder Cancer

Some patients who meet the US Food and Drug Administration (FDA) criteria for “[bacillus Calmette-Guérin (BCG)]-unresponsive” bladder cancer may benefit from additional BCG therapy, according to a study led by Amanda Myers, MD, of the University of Texas MD Anderson Cancer Center, and presented at the 2024 European Association of Urology Congress.

In 2018, the FDA formulated and adopted the category “BCG-unresponsive disease” for patients with urothelial carcinoma. This category helped facilitate single-arm registration studies for novel agents, 2 of which have subsequently been approved. “BCG-unresponsive” has been incorporated into clinical practice, and many clinicians do not offer additional BCG therapy to these patients.

Dr. Myers and colleagues designed a study to determine whether additional BCG in patients deemed “BCG-unresponsive” is warranted. They identified 163 patients diagnosed with non-muscle invasive bladder cancer from January 2000 to September 2021 with “BCG-unresponsive” disease, of whom 35 received rescue BCG as a primary treatment. Of these 35 patients, 19 had T1 disease, 7 had Ta disease, 9 had carcinoma in situ, and 8 had concomitant carcinoma in situ.

Researchers noted that 74% (n=26) of patients showed no disease after rescue BCG, and of these, 25 received maintenance therapy.

After a median follow-up of 5.9 years, Kaplan-Meier estimates of event-free survival—defined as any high-grade recurrence, progression, or death—after rescue BCG were 68% at 12 months, 62% at 24 months, and 48% at 36 months.

In the 2 years after rescue BCG, 21 patients remained with no evidence of disease, 4 progressed to muscle invasive disease, and 9 recurred without progression. Of these patients, 2 underwent cystectomy and 7 received further bladder-sparing therapies.

The cystectomy-free survival at 12, 24, and 36 months was 88%, 79%, and 79%, respectively. Similarly, progression-free survival was 91%, 88%, and 76%, respectively, while overall survival was 94%, 91%, and 85%, respectively.

“In selected patients who meet the ‘BCG-unresponsive’ definition, additional BCG therapy can demonstrate appreciable efficacy,” study authors concluded. “This challenges current paradigms, which recommend against using further BCG in these patients, and emphasizes the need for randomized, controlled trials.”