Efficacy of Urinary Mast Cell Activation Markers in Patients with Primary High-Grade Non-Muscle Invasive Bladder Cancer Treated with BCG Immunotherapy

Abstract

Mast cells play critical roles in cancer pathway. We aimed to prospectively investigate the urinary mast cell activation markers in patients with non-muscle invasive bladder cancer (NMIBC) treated with Bacillus Calmette-Guérin (BCG). Nineteen patients who were 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. Cystoscopy 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 presence of NMIBC were assessed. The average age was 56.1 ± 10.5 years. 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 mast cell activation markers 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. This is the first study to determine that urine N-methylhistamine levels increase with BCG instillation and NMIBC presence. However, urinary mast cell activation markers were not found to significantly predict the patients’ response to immunotherapy. Further studies are required to ascertain the clinical implications of these finding.