The Influence of Dietary Isothiocyanates on the Effectiveness of Mitomycin C and Bacillus Calmette-Guérin in Treating Nonmuscle-Invasive Bladder Cancer

• Published in: The Journal of urology Vol. 212; no. 3; pp. 420 - 430
• Main Authors: Kwan, Marilyn L, Wang, Zinian, Haque, Reina, Lee, Valerie S, Roh, Janise M, Ergas, Isaac J, Cannavale, Kimberly L, Pratt, Rachel, Goniewicz, Maciej, Loo, Ronald K, Aaronson, David S, Quesenberry, Jr, Charles P, Zhang, Yuesheng, Ambrosone, Christine B, Kushi, Lawrence H, Tang, Li
• Format: Journal Article
• Language: English
• Published: United States 01-09-2024
• Subjects: Adjuvants, Immunologic - therapeutic use; Aged; Antibiotics, Antineoplastic - therapeutic use; BCG Vaccine - administration & dosage; BCG Vaccine - therapeutic use; Diet; Female; Follow-Up Studies; Humans; Isothiocyanates - pharmacology; Isothiocyanates - therapeutic use; Male; Middle Aged; Mitomycin - therapeutic use; Neoplasm Invasiveness; Neoplasm Recurrence, Local - epidemiology; Neoplasm Recurrence, Local - prevention & control; Prospective Studies; Treatment Outcome; Urinary Bladder Neoplasms - drug therapy; Urinary Bladder Neoplasms - pathology; recurrence; isothiocyanate; bacillus Calmette-Guérin; nonmuscle invasive bladder cancer; cruciferous vegetable
• ISSN: 0022-5347; 1527-3792; 1527-3792
• DOI: 10.1097/JU.0000000000004070

Nonmuscle-invasive bladder cancer (NMIBC) has high recurrence rates and is often treated with mitomycin C (MMC) and bacillus Calmette-Guérin (BCG). Their efficacy relies on phase 2 enzyme metabolism and immune response activation, respectively. Dietary isothiocyanates, phytochemicals in cruciferous vegetables, are phase 2 enzyme inducers and immunomodulators, and may impact treatment outcomes. We investigated the modifying effects of cruciferous vegetable and isothiocyanate intake on recurrence risk following MMC or BCG treatment.
Self-reported cruciferous vegetable intake, estimated isothiocyanate intake, and urinary isothiocyanate metabolites were collected from 1158 patients with incident NMIBC in the prospective Be-Well Study. Hazard ratios (HRs) and 95% CIs were calculated from Cox proportional hazards regression models for risk of first recurrences, and random effects Cox shared frailty models for multiple recurrences.
Over median follow-up of 23 months, 343 (30%) recurrences occurred. Receipt of MMC and BCG was associated with decreased risks of first recurrence (MMC: HR = 0.58; 95% CI: 0.46-0.73; BCG: HR = 0.66; 95% CI: 0.49-0.88) and multiple recurrences (MMC: HR = 0.55; 95% CI: 0.44-0.68; BCG: HR = 0.72; 95% CI: 0.55-0.95). Patients receiving BCG and having high intake (>2.4 servings/mo), but not low intake, of raw cruciferous vegetables had reduced risk of recurrence (HR: 0.56; 95% CI: 0.36-0.86;
for interaction = .02) and multiple recurrences (HR: 0.51; 95% CI: 0.34-0.77;
for interaction < .001). The inverse association between MMC receipt and recurrence risk was not modified.
For NMIBC patients who receive induction BCG, increasing consumption of raw cruciferous vegetables could be a promising strategy to attenuate recurrence risk.