Efficacy of Urinary Mast Cell Mediators in Patients with Primary
High-Grade Non-Muscle Invasive Bladder Cancer Treated with BCG
Immunotherapy
Abstract
Background: Mast cells play a critical role in tumor-associated immune
pathways. We aimed to prospectively investigate the urinary mast cell
mediators in patients with non-muscle invasive bladder cancer (NMIBC)
treated with Bacillus Calmette-Guérin (BCG) immunotherapy. Methods:
Nineteen patients who have received immunotherapy due to NMIBC and 19
healthy participants were enrolled. Urine samples were collected to
assay N-methylhistamine, histamine and tryptase levels immediately
before the first BCG instillation, immediately after the third and sixth
instillations, and four weeks after the sixth instillation in patients
with NMIBC and at a single visit in healthy participants. Cystoscopic
examinations were performed on the patient with NMIBC at three-month
intervals for two years. The changes in urinary markers due to BCC
response, BCG instillation, and the presence of NMIBC were assessed.
Results: The average age was 56.1 ± 10.5 years in patients with NMIBC.
Fourteen patients had high-grade Ta tumors, and 5 had high-grade T1
tumors. While 12 patients responded, 6 presented with recurrence and 1
with progression. There was no correlation between the levels of mast
cell mediators and BCG response. The N-methylhistamine and histamine
levels were increased significantly with the onset of immunotherapy and
N-methylhistamine levels were decreased significantly when immunotherapy
was terminated. Pre-BCG estimated marginal means of N-methylhistamine
were significantly higher in patients with NMIBC than healthy
participants. Conclusions: This is the first study to determine that
urine histamine and N-methylhistamine levels showing the change with
immunotherapy. However, these mediators were not found to predict the
patients’ response to immunotherapy.