Introduction:

Bacillus Calmette-Guerin (BCG) is the most effective therapy available to treat high-risk non-muscle invasive bladder cancer (NMIBC) patients.  However, for immunosuppressed patients BCG is a relative contraindication due to efficacy and safety concerns.  To our knowledge, no population-level study evaluating the efficacy and safety profile of BCG for immunosuppressed patient exists.

Methods:

Non-muscle invasive bladder cancer patients aged 66 years or older were identified in the Surveillance, Epidemiology, and End Results (SEER) – Medicare database from 1975 — 2013. All patients completed adequate BCG (at least 5 plus 2 treatments completed within 12 months of diagnosis). Two groups were defined: an immunosuppressed population identified by immune compromising conditions such as solid-organ transplantation, HIV, and autoimmune conditions, and an immunocompetent group. The primary endpoint was a 5-year disease progression endpoint defined as progression to systemic chemotherapy, checkpoint inhibitors, radical or partial cystectomy, metastasis, or cancer-specific death. A safety analysis was performed as a secondary outcome.

Results:

In a total of 4,277 patients with NMIBC who completed adequate BCG, 606 (14.2%) were immunosuppressed. The immunosuppressed group was older at diagnosis (p < 0.001), more likely to be female (p < 0.001), more likely to live in a metropolitan area (p < 0.001) and had higher Charlson comorbidity scores (p < 0.001). There were no differences in progression to chemotherapy (p = 0.17), checkpoint inhibitors (p > 0.99), radical cystectomy (p = 0.40), partial cystectomy (p = 0.93), metastasis (p = 0.19), cancer-specific death (p = 0.18) or 5-year total bladder cancer progression (p = 0.30) between the groups. For the safety analysis, rates of disseminated BCG were similar between immunosuppressed and immunocompetent patients (0.7% v <1.8%, p = 0.51). On multivariable analysis 5-year total bladder cancer progression (HR 1.07 [CI 0.88 – 1.30]) was similar between the groups.

Conclusion:

Rates of bladder cancer progression and disseminated BCG complications 5-years after BCG therapy were similar regardless of immunosuppression status. These findings suggest that BCG intravesical therapy can be offered to immunosuppressed patients with high-risk NMIBC although theoretical infectious complication risks remain.

Funding: This study was supported by Grant Number P30 CA015083 from the National Cancer Institute (NCI) and from the Mayo Clinic Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, the Christian Haub Family Career Development Award for Cancer Research Honoring Dr. Richard Emslander, Eric and Gail Blodgett and the Endras Family.