Impact of Agent Orange Exposure on Non-muscle Invasive Bladder Cancer Outcomes

Abstract

To explore the effect of Agent Orange (AO) exposure on bladder cancer (BCa) outcomes in patients receiving Bacillus Calmette-Guérin (BCG) for non-muscle invasive BCa (NMIBC). We retrospectively examined the association between AO exposure in patients with NMIBC in national veterans affairs databases who were being treated with BCG. Patients were diagnosed with NMIBC from 2000 to 2010 with follow-up through 2018. Clinical, pathological, and demographic variables were compared by AO exposure. Associations of AO exposure with recurrence, progression, and cancer-specific survival were performed using Cox proportional hazard models after inverse propensity score weighting and competing risks adjustments. We also assessed the association of AO exposure on grade and stage via multivariable logistic regression models. A total of 7651 patients were identified of which 753 (9.8%) were exposed to AO. The median follow-up time was 130months. The AO-exposed patients were younger (age 61 vs 71years, P<.001), but had similar Charlson comorbidity scores and stage/grade distribution as the non-AO exposed patients. AO exposure was not associated with higher grade or stage. In our Cox multivariable analyses, AO exposure was not associated with worse recurrence (hazard ratio (HR) 0.89, 95% confidence interval (CI) 0.72-1.10, P=.29), progression (HR 1.08, 95% CI 0.86-1.36, P=.51), or cancer-specific survival (HR 1.31, 95% CI 0.92-1.87, P=.13). AO exposure was not associated with worse oncologic outcomes in patients receiving BCG for NMIBC. While this is reassuring, additional research is needed in other patient populations and disease states to determine if the effect is consistent.