The Impact of Agent Orange Exposure on Bladder Cancer
Agent Orange (AO) is a mixture of herbicides used during the Vietnam War to clear forest cover that concealed opposition forces and destroy crops. In 2014, the National Academy of Sciences reported that epidemiologic data was suggestive of an association between bladder cancer and AO exposure, based on evidence that higher levels of exposure are associated with an approximately 2-fold increase in death from bladder cancer. There is little data regarding whether this is due to increased incidence, more aggressive disease or other factors. Additionally, some of the prior data did not account for tobacco use, another potential contributor to bladder cancer carcinogenesis and progression.
Vietnam-era veterans who had been diagnosed and/or treated for urothelial carcinoma of the bladder (UCB) at the Minneapolis VA Medical Center were identified. We reviewed the medical charts of included patients to examine pathologic stage and grade at diagnosis and identify those who experienced recurrence, progression, cystectomy and death from disease. Patients who left the VA prior to death were censored at the date of their last cystoscopic evaluation. Patients who developed metastatic or muscle invasive bladder cancer were not included further in analysis for recurrence and progression, but only followed beyond this point to determine if death occurred from UCB. Charts were also reviewed for exposure to AO, age and smoking status at the time of diagnosis.
258 patients who met the criteria were identified, with a median follow-up of 44 months. Median age was 66 years (range 44-85). 48% of patients had documented AO exposure based on Veterans Administration registration criteria. The majority of the cohort had high-grade UCB (57%), and 50% had AUA high risk disease at presentation. Recurrence occurred in 120 (46.5%), progression in 36 (14%) and 25 (9.7%) died of disease. AO exposure was associated with high grade disease at presentation on univariate and multivariate analysis when accounting for age and smoking status (OR 2.125; 95% CI 1.264, 3.572; p=0.004). AO exposure was not significantly associated with stage, recurrence, progression, cystectomy or death from UCB, though low event number likely influenced some of these analyses.
In our cohort of Vietnam-era veterans with UCB, AO exposure was associated with an approximately 2-fold increased risk of high grade disease at presentation. Further evaluation in larger cohorts is needed to better understand the mechanism leading to increased risk of death from UCB demonstrated in other studies.