AUA 2018: The Impact of Agent Orange Exposure on Bladder Cancer

San Francisco, CA (UroToday.com) Agent Orange is a mixture of herbicides that were used during the Vietnam War to clear forest coverage that concealed opposition forces. Although early studies suggested that Agent Orange increases the risk of prostate cancer [1], more contemporary studies suggest that a correlation between Agent Orange exposure and risk of prostate cancer is not as concrete [2].  Less studied, is the potential impact of Agent Orange exposure and increased risk of bladder cancer. However, in 2014, the National Academy of Sciences reported that epidemiologic data was suggestive of an association between bladder cancer and Agent Orange exposure, based on evidence that higher levels of exposure are associated with an approximately 2-fold increase in death from bladder cancer (although as of 2016, it has since backed off of these concrete statements). To further assess a potential association between Agent Orange exposure and bladder cancer, Vikram Narayan, MD, and colleagues from the University of Minnesota presented results of their institutional study. As Vikram points out, there is little data regarding whether a perceived association between Agent Orange and bladder cancer is secondary to increased incidence, more aggressive disease or other factors, as well as taking into account prior/present tobacco use.

For this study, the authors identified Vietnam-era veterans diagnosed and/or treated for bladder cancer at the Minneapolis VA Medical Center. Specific variables and outcomes of interest included:

  1. Exposure to Agent Orange 
  2. Age
  3. Smoking status at diagnosis
  4. Pathologic stage and grade at diagnosis
  5. Recurrence, progression, cystectomy or death secondary to bladder cancer 
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 subsequently followed to determine if death occurred from bladder cancer. 

There were 258 patients who met inclusion criteria for this retrospective study, with a median follow-up of 44 months. There were 48% of patients having documented Agent Orange exposure based on Veterans Administration registration documentation; median age was 66 years (range 44-85). Most patients had high-grade bladder cancer (57%), and 50% had AUA high-risk disease at presentation. Recurrence occurred in 120 (46.5%) patients, progression in 36 (14%) and 25 (9.7%) died of disease. Agent Orange exposure was associated with high-grade disease at presentation when accounting for age and smoking status (OR 2.13, 95%CI 1.26-3.57), although was not associated with stage, recurrence, progression, cystectomy or death from bladder cancer. 

AgentOrange Exposure

The results presented by Vikram and colleagues are important in delineating further granularity with regards to the epidemiology of Agent Orange exposure and bladder cancer. These results certainly are of interest to policymakers within the Veterans Administration, considering that patients with war-time related carcinogenic exposures are often assigned increased coverage and benefits through the VA system. The authors acknowledge that one of their limitations is that there were low numbers of events for recurrence, progression, cystectomy or death from bladder cancer, thus a true association between Agent Orange and these outcomes was not discernable in the current study, but may, in fact, be true. Vikram concluded that their study suggests that Agent Orange exposure is associated with a ~2-fold increased odds of high-grade disease at presentation. They note that future larger studies are needed to better understand the mechanism leading to increased risk of death from bladder cancer, as demonstrated in other studies [3].

Presented by: Vikram Narayan, MD, University of Minnesota, Minneapolis, MN
Co-Authors: Michael Risk, Cesar Ercole, Minneapolis, MN

References:
1. Shah SR, Freedland SJ, Aronson WJ, et al. Exposure to Agent Orange is a significant predictor of prostate-specific antigen (PSA)-based recurrence and a rapid PSA doubling time after radical prostatectomy. BJU Int 103(9):1168-1172.
2. Ovadia AE, Terris MK, Aronson WJ, et al. Agent Orange and long-term outcomes after radical prostatectomy. Urol Oncol 2015;33(7):329.e1-6.
3. Mossanen M, Kibel AS, Goldman RH. Exploring exposure to Agent Orange and increased mortality due to bladder cancer. Urol Oncol 2017;35(11):627-632

Written by:  Zachary Klaassen, MD, Urologic Oncology Fellow, University of Toronto, Princess Margaret Cancer Centre at the 2018 AUA Annual Meeting - May 18 - 21, 2018 – San Francisco, CA USA
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