Wednesday, March 19, 2014

Agent Orange and aggressive prostate cancer

Veterans exposed to Agent Orange have an increased risk of aggressive prostate cancer, analysis finds
May 27, 2013
By Angela Townsend, The Plain Dealer 

* Dioxin in a Drum (2,4,5 T + 2,4 D) = AO
CLEVELAND, Ohio -- A veteran of the U.S. Air Force and the Air Force Reserve before his retirement in 2005, Terry Dillon served in Vietnam as a member of the 14th Air Commando Wing at Nha Trang Air Base.

He was there for only one year, from June 1967 to June 1968, but it was long enough to potentially affect Dillon's health decades later.

Millions of Vietnam War veterans were exposed to Agent Orange, an herbicide that contained dioxin and other dangerous toxins and potential cancer-causing agents. Throughout the 1960s until 1971 in Vietnam (as well as in the Korean Demilitarized Zone and, until 1975, in some parts of Thailand), the military used the herbicide to wipe out the foliage and trees to impede the enemy's ability to hide.

"Nobody thought a thing about it," said Dillon, 68, of suburban Columbus. "Basically we knew they were defoliating the jungle areas, but no one I talked to thought there was anything bad about the stuff.

"[Agent Orange] was the least of our worries, we would be hit with mortars and 122 mm rockets," he said.

In 1981, Dillon was diagnosed with and treated for testicular cancer, but he didn't link his disease with exposure to Agent Orange.

Not until the late 1990s did some of his fellow Air Force vets start having health problems, and start considering if there was a possible link to their time in Vietnam.

In 2008, at age 63, Dillon had the prostate-specific antigen, or PSA, blood test for the first time after complaining to his primary physician of fatigue.

That year he was diagnosed with prostate cancer.

The majority of cases are slow-growing tumors considered to be "low-grade." Dillon soon found out that he had the more aggressive, metastatic kind considered "high-grade."

Upon receiving the news, he, too, started to ask military officials if Agent Orange could be the cause.

The National Cancer Institute estimates that there will be 238,590 new cases of prostate cancer in 2013, and 29,720 deaths this year in the United States.

The U.S. Department of Veterans Affairs lists prostate cancer as one of 14 diseases -- including Type 2 diabetes and Parkinson's -- associated with exposure to Agent Orange.

For years, oncologists have included Agent Orange exposure in the "potential risk factor" category for prostate cancer.

"Prostate cancer had been studied in U.S. veterans previously, but these studies were done when the veterans were relatively young. Likely too young to have provided an answer as to whether prostate cancer risk was increased or not," said Dr. Mark Garzotto, a surgeon at the Portland VA Medical Center and Oregon Health & Science University and lead author of an article that was published earlier this month in the journal Cancer. "Our study was primarily in men who were in their 60s, thus of the age at which prostate cancer develops."

Garzotto said he and his colleagues were interested in two main questions: Is the incidence of prostate cancer increased in men who were exposed to Agent Orange? If that answer is yes, was the change due to an increase in low-grade cancer, high-grade cancer or both?

They looked at a group of 2,720 military veterans (93.6 percent white, 3.8 percent black), to see if they had a higher risk of developing high-grade prostate cancer -- defined as registering a Gleason score (a grade based on how fast cancer might spread) of 7 or higher on an initial biopsy.

The historical statistical analysis found:
• Of all veterans who underwent a prostate biopsy procedure, 203 (7.5 percent) had been exposed to Agent Orange. 
• Of the 896 vets (32.9 percent) who had been diagnosed with prostate cancer, 74 (8.2 percent) had Agent Orange exposure. 
• Of the 459 vets (16.9 percent) who had high-grade disease, 40 (8.7 percent) had Agent Orange exposure.
The study found that overall rates of prostate cancer were increased in veterans exposed to Agent Orange. That exposure was statistically linked with a 52 percent increase in overall risk of prostate cancer detection by biopsy.

That increase, however, was driven purely by the increased risk -- by 75 percent -- in the high-grade or lethal prostate cancer subtype, Garzotto said. And the risk of potentially lethal cancer (a Gleason score of 8 or higher) in men exposed to Agent Orange increased 110 percent over men who were not exposed.

Men with exposure

should consider screening

The majority of prostate cancer is slow-growing in nature; a patient diagnosed in his 60s or 70s with a less-aggressive form is more likely to die of something else. But the researchers say their findings are prompting them to advise men with a history of Agent Orange exposure to talk to their physicians and strongly consider prostate cancer screening.

"We are working with the U.S. Preventive Task Force within the VA to incorporate these findings into current screening practices," Garzotto said. The next steps for the research will include evaluating the effect, if any, that a man's Agent Orange exposure has on how he responds to treatments such as surgery and radiation.

Because of previous radiation treatment for testicular cancer, and because his advanced prostate cancer didn't make him a good candidate for a prostatectomy (the removal of the prostate gland and surrounding tissue), Dillon was treated with cryoablation. Cryoablation, or cryotherapy, uses liquid nitrogen to freeze and destroy cancerous tumors.

After the first treatment, Dillon's PSA levels fell to zero. But in early 2012, his PSA levels started rising again. His cancer had reappeared, and by late 2012 his Gleason score was close to 9.

Dillon's urologist in Columbus recommended going elsewhere for more specialized care. He was eventually referred to Dr. J. Stephen Jones, chief of surgical operations at Cleveland Clinic's Fairview Hospital.

"Dr. Jones kind of reminds me of a fighter pilot," Dillon said. "He's really self-assured and confident about what he's doing."

Jones performed Dillon's second cryoablation on Feb. 28.

Data compelling,

doctor says

"Prostate cancer historically has not been linked to environmental factors as much as other cancers [such as lung or bladder] but these data are starting to become compelling," said Jones, who counts a small number of men exposed to Agent Orange among his patients.

"I haven't seen huge numbers, but now it's not at all uncommon," he said.

The analysis published in the journal Cancer is from a relatively small patient population that wasn't chosen randomly, but that doesn't diminish the significance of the results, Jones said.

The biggest surprise to come from the analysis, he said, was the increase in high-grade prostate cancer as opposed to the low-grade disease.

"A lot of men will start developing issues [related to] prostate cancer in their 20s, but it typically takes years to develop," he said. "Screening is the key thing. If we have a patient exposed [to Agent Orange], clearly they are definitely in a potential risk category. That seems compelling to me."

There is some evidence that a man can reduce his risk by taking certain drugs that lower the levels of testosterone and other male hormones that can contribute to the growth of prostate cancer. But there remains some controversy that those drugs still pose a slight increased risk of someone developing high-risk prostate cancer.

As to whether someone exposed to Agent Orange would benefit from taking the drugs, Jones said, "We just don't have the data to answer that question."

So far, Dillon has remained cancer-free. He is getting PSA tests every three months and will have a follow-up visit with Jones in August.

"I'm not a doctor, I'm not a chemist, but I'm pretty sure [Agent Orange] had something to do with it," Dillon said.

"I wouldn't do anything any different. We didn't have the data. I feel like nobody really knew exactly how dangerous the stuff was."


RISK FACTOR FOR VETERANS


An excerpt from the analysis of Agent Orange exposure on prostate cancer in the journal Cancer: "Vietnam veterans are now reaching their mid-60s, the age at which new cases of prostate cancer are most commonly diagnosed in the United States. To more accurately assess the latent effects of Agent Orange on prostate cancer risk, a reassessment of contemporary biopsy data is needed. "Roughly 8 million men in the United States are veterans of the Vietnam War. On the basis of national prostate cancer rates between 2005 and 2007, it is predicted that nearly 1.4 million of these men will develop prostate cancer during their lifetime. Although no real estimates exist for the percentage of Vietnam veterans who experienced Agent Orange, roughly 3 million veterans served in Southeast Asia alone, where Agent Orange was used extensively in the combat theater . . . "The U.S. Preventive Services Task Force guideline panel has recently recommended against population-based PSA screening; however, it is important to note that the effect of Agent Orange was not addressed by the task force." --"Agent Orange as a Risk Factor for High-Grade Prostate Cancer," in the journal Cancer
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