Prostate Cancer Recurrence Linked to Agent Orange Exposure

Nick Mulcahy

April 22, 2009

April 22, 2009 — Vietnam veterans who undergo radical prostatectomy and who were exposed to Agent Orange are at increased risk for biochemical recurrence of prostate cancer. These veterans also had a shorter prostate-specific antigen (PSA) doubling time than veterans who underwent the procedure but who were not exposed to the toxic defoliant, researchers report in the May issue of BJU International.

The new study confirms an earlier similar finding in Vietnam veterans exposed to Agent Orange, which was presented at the American Urological Association annual meeting in 2007.

However, the clinical significance of the findings is not clear, the authors note. "These findings suggest that among selected men who chose radical prostatectomy, Agent Orange exposure might be associated with more aggressive prostate cancer," they write.

Nevertheless, the findings should be a red flag for clinicians who treat Vietnam veterans, suggested the study's senior author, Martha Terris, MD, chief of urology at the Charlie Norwood VA Medical Center, in Augusta, Georgia, in a statement. Dr. Terris is also professor of urology at the Medical College of Georgia School of Medicine.

"There is something about the biology of these cancers that are associated with prior Agent Orange exposure that is causing them to be more aggressive. We need to get the word out," said Dr. Terris.

We need to get the word out.

Dr. Terris advises clinicians to be proactive with Vietnam veterans with regard to prostate cancer. "I encourage fellow clinicians to screen Vietnam veterans for prostate cancer and follow them closely for recurrence following treatment," she told Medscape Oncology.

The development of "aggressive" biochemical recurrence was also troubling because the affected patients' tumors initially had low-risk features, the study authors write.

Dr. Terris said that biochemical recurrence "can decrease overall survival, require additional therapy, and/or impact quality of life."

However, one prostate cancer expert has noted that biochemical recurrence after definitive therapy is common and is often associated with an excellent prognosis, as reported by Medscape Oncology .

Still, as the authors noted, there seems to be a link between Agent Orange exposure and prostate cancer. A study of United States Air Force veterans indicated that exposure to Agent Orange was associated with a greater risk of developing prostate cancer in white veterans, compared with age-matched controls, and that the risk was greater among white veterans with higher serum levels of dioxin (a component of Agent Orange), write the authors.

In the new study, biochemical recurrence affected exposed blacks and whites. "When stratified by race, the association between Agent Orange exposure and poor outcomes was equal between the races," the authors write.

It is unclear how possible erroneous claims may affect the results.

The study also had a unique limitation: there was no quantification of levels of dioxin or Agent Orange because tests to determine very low levels of dioxin are still in development. Thus, the status of the exposure was "purely subjective." Furthermore, the veterans potentially had "financial incentives (compensation for healthcare and disability from the federal government) to associate their diagnosis with a history of Agent Orange exposure," write the authors.

"It is unclear how possible erroneous claims may affect the results," noted Dr. Terris.

Results Further Reviewed

The study comprised 1495 veterans with prostate cancer who underwent radical prostatectomy, 206 of whom were exposed to Agent Orange. After the researchers adjusted for several clinical factors, they found that the exposed patients had a 45% increased risk of their cancer biochemically recurring (relative risk, 1.55; 95% confidence interval, 1.15 - 2.09; = .004). The exposed veterans also had a shorter median PSA doubling time (8.2 vs 18.6 months; < .001) than the other veterans in the study.

Despite these notable differences between the 2 patient groups, Agent Orange exposure was not significantly related to adverse pathologic features, such as Gleason scores, positive surgical margins, or seminal vesicle invasion, note the authors.

However, the 2 groups had other differences. The men with Agent Orange exposure were more likely to be black (= .001) and younger (<.001), and to have a higher body mass index (= .001), clinical stage T1 disease (< .001), and lower preoperative PSA levels (= 001).

The study was funded by the Department of Veterans Affairs, the National Institutes of Health, the Georgia Cancer Coalition, the Department of Defense Prostate Cancer Research Program, and the American Urological Association/Astellas Rising Star in Urology Award. The researchers have disclosed no relevant financial relationships.

BJU Int. 2009:103;1168-1172.

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