Presentation Authors: Michael B. Rothberg*, Wenjun Le, Ronald L. Davis, Zheng Cui, Winston-Salem, NC
Introduction: Intravesical instillation of Bacillus Calmette-Guerin (BCG) is the most effective therapy for non-muscle invasive bladder cancer (NMIBC); however, one-third of patients receiving treatment with BCG fail to respond. Identifying non-responders prior to BCG treatment would better utilize this resource and prevent delay of receipt of second line therapies. We sought to evaluate the ability of a novel blood-based assay to predict clinical response to intravesical BCG.
Methods: Eligible patients with biopsy-confirmed NMIBC provided a 10cc blood sample prior to BCG treatment. Leukocytes were fractionated into granulocytes and mononuclear cells with â‰¥97% purities. Leukocytes were co-cultured with target cancer cells in the presence of either BCG or E. coli. The cancer killing activity (CKA) of leukocytes, driven by in vitro stimulation from live bacteria, against several cancer cell lines over a 24-hour period was determined.
Results: Of the nineteen patients enrolled, ten patients had a definitive clinical response to intravesical BCG, while five patients were definitive non-responders. Four patients had indeterminate clinical responses. When clinical outcomes were compared to twelve different assay combinations of leukocytes, cancer cells, and bacteria, the CKA from the granulocytes, 5637 bladder cancer cells, and BCG co-cultures gave correct predictions of response to intravesical BCG for twelve of fifteen patients and the CKA from the granulocytes, J82 bladder cancer cells, and BCG co-cultures gave correct predictions of response to intravesical BCG for ten of fifteen patients.
Conclusions: The clinical response to intravesical BCG treatment may be predictable using this novel blood-based assay and warrants further investigation.
Source of Funding: Department of Pathology, Wake Forest School of Medicine