Introduction:

There is a lack of data on the patterns of treatment of patients with non-muscle invasive bladder cancer (NMIBC) who are BCG unresponsive in the US urologic community. It is crucial to know what treatment decisions and protocols are used when intravesical chemotherapy is given to these patients. Likewise, the tumor type (papillary vs. carcinoma in situ (CIS)) may influence the choice of these chemotherapy regimens. The goal of this survey was to evaluate the treatment and practice patterns of urologists treating high-grade (HG)  papillary-only tumors and CIS in the BCG-unresponsive space. Especially considering the current BCG shortage, we wanted to know how use varied in those with adequate BCG exposure and those with less than adequate BCG exposure. This may also help to understand when and where rescue bladder-sparing therapies are used instead of radical cystectomy (RC).

Methods:

An internet-based survey with a target duration of 5 minutes was sent to US urologists who manage patients with BCG-unresponsive NMIBC. Respondents were recruited from a target list based on high BCG utilization. One survey asked about the treatment of patients with CIS and was fielded from January 6–19, 2022. The second one asked about the management of patients with papillary-only tumors and was fielded from April 12–18, 2022.  Both surveys focused on intravesical chemotherapy use in BCG-unresponsive patients with adequate and less than adequate BCG exposure. When intravesical chemotherapy was used, the induction and maintenance regimens used by each urologist was also documented. Additional questions were asked about what urologists considered as clinically meaningful efficacy for each patient’s group. The study was essentially descriptive, and the percentage of patients in each group were used to represent categorical variables.

Results:

100 urologists managing patients with HG BCG-unresponsive papillary-only tumors and 159 urologists managing  BCG-unresponsive CIS completed the survey. Most (78%) were community-based and just over half listed chemotherapy as their preferred treatment with under one-third choosing RC and roughly 15% selecting systemic immune therapy. The median minimal efficacy for perceived clinical benefit was 35%. For CIS patients with adequate BCG, the rank order was 40% Gemcitabine (Gem), 28% mitomycin-C (MMC), 19% Valrubicin (Val), 8% Gemcitabine/Docetaxel (Gem/Doce) and 5% other. A very similar profile was seen for CIS with inadequate BCG exposure. For BCG-unresponsive papillary-only disease, the rank order was slightly different: Gem 49%, MMC 23%, Gem/Doce 15%, Val 11% and other 2%. Chemotherapy choices for those with inadequate BCG exposure was similar except for an uptick in Gem to 57% and downtick in Gem/Doce to 10%. Maintenance therapy was preferred for Gem and MMC but the regimens varied considerably

Conclusion:

The most common treatment endorsed by this recent sampling of US urologists for BCG-unresponsive NMIBC was intravesical single agent chemotherapy, with Gem or MMC accounting for roughly 70% of the chemotherapy total. This practice pattern was similar regardless of BCG exposure or whether treatment was for CIS or papillary-only tumors. RC was widely underutilized as was doublet Gem/Doce therapy despite emerging evidence of its increasing use among bladder cancer specialists. This practice pattern unlikely reflects the current BCG shortage since BCG adequacy had minimal impact on preferred choices. Drug availability, familiarity and ease of office use may be stronger drivers since supporting medical evidence, especially for BCG-unresponsive CIS, is notably lacking. Considering the rapid pace at which new therapies in the BCG-unresponsive space are being developed, it behooves clinical trialists and urologic oncologists to provide updated information and guidelines to the general urologic community in this important clinical arena. 

Funding: N/A