Response and Outcomes to Immune Checkpoint Inhibitors in Advanced Urothelial Cancer Based on Prior Intravesical Bacillus Calmette-Guerin - Beyond the Abstract

Intravesical bacillus Calmette-Guerin (BCG) became the first Food and Drug Administration (FDA) approved immunotherapy in 1990 based on SWOG 8216 and SWOG 8507 trials. This changed the treatment landscape of non-muscle invasive bladder cancer (NMIBC). Unfortunately, a significant proportion of these patients with NMIBC may have tumor progression to advanced urothelial carcinoma (aUC). Immune checkpoint inhibitors (ICI) can prolong overall survival in patients with aUC after platinum-based chemotherapy, either as switch maintenance or salvage therapy, and are considered a standard of care. However, there have not been many studies investigating the potential association between prior intravesical BCG for NMIBC and the efficacy of ICI in aUC.

In our large multi-institution retrospective study across sites in the US and Europe, we compared clinical outcomes with ICI therapy in patients with aUC who had received prior intravesical BCG for NMIBC vs those without prior exposure to intravesical BCG. We hypothesized that those with prior intravesical BCG exposure would have aUC less sensitive to ICI, and thus have lower response rates and shorter overall and progression-free survival. Interestingly, our study revealed that prior intravesical BCG exposure was not associated with a significant difference in overall response rate, progression-free, or overall survival in patients with aUC treated with ICI. A possible explanation is that while BCG and ICI are both considered immunotherapy modalities, they have different mechanisms of action, routes of administration, clinical indications, timing in relation to disease stage, dosing schedule, and, possibly, pathways of resistance.

Our results seem reassuring that patients with aUC and prior intravesical BCG therapy may benefit to a similar degree to ICI therapy as those without such prior therapy. Our study had several limitations inherent to its retrospective and not randomized design, lack of quantification of intravesical BCG (such as number of cycles, dosing, etc.), the timing of intravesical BCG therapy relative to subsequent ICI, as well as potential selection and confounding biases. Future studies investigating the efficacy of ICI in urinary tract cancers may consider subset analyses further evaluating whether prior BCG exposure may affect response and outcomes to ICI therapy.

Written by: Rafee Talukder, MD,1 Dimitrios Makrakis, MD,1 Ali Raza Khaki, MD, MS,2 Petros Grivas, MD, PhD1

  1. University of Washington, Seattle, WA
  2. Stanford University School of Medicine, Palo Alto, CA

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