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PROSTATE CANCER NEWSLETTER - May 2009

Vitamin E, Selenium and Soy Won't Prevent Prostate Cancer
Study found no effect among men with precancerous lesions.

Despite earlier promise, three nutrients - vitamin E, selenium and soy - do not seem to prevent prostate cancer in men with precancerous prostate lesions, Canadian researchers report.

"There has been a collection of scientific data that has suggested that these agents could have a tremendous impact in preventing prostate cancer," said lead researcher Dr. Neil E. Fleshner, a Clinical Studies Resource Centre Member at the Ontario Cancer Institute and Love Chair in Prostate Cancer Prevention at the University of Toronto.

"So there was great hope that this would be a magic bullet that would help prevent prostate cancer," he said. "Unfortunately, it doesn't appear to be so."

The report was to be presented Sunday at the American Urological Association's annual meeting, in Chicago.

For the study, Fleshner's team randomly assigned 303 men with high-grade prostatic intraepithelial neoplasia (precancerous lesions) to receive soy protein, vitamin E and selenium, or a placebo. Over three years, the men had several biopsies to determine if they had developed prostate cancer.

Just over 26 percent of the men did develop invasive prostate cancer. However, the three nutrients did not seem to minimize that risk, the team found.

"To recommend soy and these supplement to men with high-grade prostatic intraepithelial neoplasia really doesn't make much sense, if the reason you are giving it is to prevent your patient from developing invasive cancer," Fleshner concluded.

He did leave the door open to using these supplements to prevent prostate cancer before precancerous lesions have formed. "In pre-cancer, the cells may already be so damaged that supplements can't reverse the changes," he reasoned. "Or maybe it just doesn't work."

The results confirm the findings of the two recent prospective trials, which also found that vitamin E, vitamin C and selenium do not prevent prostate cancer. The results of these trials were published in the Jan. 7 issue of the Journal of the American Medical Association. Other recent studies have suggested that vitamins, B, C, D, E, folic acid and calcium taken alone, or in various combinations, aren't effective for cancer prevention.

"Single-agent interventions, even in combinations, may be an ineffective approach to primary prevention in average-risk populations," wrote Dr. Peter Gann, author of an accompanying Journal of the American Medical Association editorial.
However, one expert believes that while vitamins E and C may not prevent prostate tumors, soy might still prove to be of benefit.

"There is some evidence from laboratory and population studies that soy protein or its components might reduce risk of prostate cancer," said Eric Jacobs, strategic director for Pharmacoepidemiology at the American Cancer Society.

In this study, soy protein had no apparent effect on the development of prostate cancer among men who already had precursor lesions in the prostate, Jacobs noted. "However, it remains possible that soy could reduce risk of developing prostate cancer by inhibiting earlier stages of prostate cancer development, or that soy could reduce the risk of recurrence or disease spread in men with prostate cancer," he said.

Douglas MacKay is vice president for Scientific & Regulatory Affairs at the Center for Responsible Nutrition, which represents the supplements industry. He believes the role of supplements is complex and trying to find a pill that will prevent cancer is a hopeless task. However, supplements and a healthy lifestyle can both play a role in helping patients prevent or fight cancer, MacKay said.

"Soy isoflavones and other dietary supplements may help prevent the development of cancer," MacKay said. "Men should include these things as part of a healthy lifestyle and integrated approach to preventive medicine. However non-pharmacologic dietary preventions, whole foods, extracts and herbs' influence on the development of cancer is complex and may not be appropriately tested using a randomized clinical trial."

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Biomarkers May Predict Aggressiveness of Prostate Cancer
Cancer expert is wary of finding, however

Three molecules associated with prostate cancer might provide the long-sought markers that could discern which tumors are life-threatening and need aggressive treatment, a new study indicates.

The currently hot debate about the value of screening for early detection of prostate cancer hinges on the fact that the cancer is usually so slow-growing that there is no lifesaving benefit from treatment such as surgery, which can cause impotence and incontinence. Recent studies in the United States and Europe found at best limited benefit from routine prostate cancer screening, and new guidelines from the American Urological Association say that many men do not need annual screening tests.

As yet, there are no established markers to distinguish which prostate cancers grow fast enough to require such treatment. The new study, published in the May 5 issue of the Annals of Internal Medicine, identifies three such markers.

"We're not trying to say these are the only markers," said study author Dr. John Concato, a professor of medicine at Yale University and director of the clinical epidemiological research for the Veterans Affairs Connecticut Healthcare System. "This is a proof of principle."

Measuring levels of the markers might someday help guide treatment of men with prostate cancer, he said. "If the markers are positive, that might be an indication that more aggressive therapy is indicated," Concato said.

However, that claim was challenged in an accompanying editorial by a cancer specialist.
The findings stemmed from an examination of tissue samples from 1,172 men diagnosed with prostate cancer at VA centers in New England. Researchers looked at a number of possible biomarkers and identified three associated with a higher risk of death from the cancer: bcl-2, a molecule that helps regulate cell death; p53, a protein produced by a tumor-suppressor gene; and microvessel density, the excessive production of blood vessels needed for growth of a cancer.

Levels of all three markers were significantly higher in the men who died of prostate cancer in the subsequent 11 to 16 years, the study found.
Concato said the study is just a first step toward use of the biomarkers to guide prostate cancer treatment. "Other groups should replicate our results," he said. "Based on these results, there should be an effort at developing therapies that attack the mechanisms reflected by these markers."

Concato said he has proposed a clinical trial that "would treat patients based on marker status, as positive or negative."
The editorial by Dr. Edward P. Gelmann, chief of the division of hematology/oncology and deputy director of the Herbert Irving Comprehensive Cancer Center at Columbia University, challenged the value of all three biomarkers.

A number of previous studies have shown that results of p53 tests "are not reproducible from one laboratory to the next," Gelmann said. "There is great variability in both technique and results." Though p53 has been studied as a biomarker for a number of cancers, he said, it is used only for one rare malignancy, transitional cell carcinoma of the blood.

As for bcl-2, Gelmann said that the number of cases in the study with a positive reading was too small to provide proof of its predictive power. "To prove it has prognostic significance would require would require a larger trial," he said.

And the measure of blood vessel density done in the study was not necessarily reproducible, Gelmann said. "It was done by an individual observer without anyone else checking it," he said.
In response, Concato said that "the editorial doesn't mention several major strengths of the study, and it misrepresents what was known before we did our study."

"For example, showing a link between markers taken at diagnosis and long-term mortality had not been shown before," he said. "Perhaps the editorial is concerned about inappropriate, excessive use of these markers -- and, if so, we would agree."

Younger men diagnosed with advanced prostate cancer don't live as long as older men facing the same diagnosis, a new study finds.

"Overall, young men with prostate cancer do quite well, although the young men that have more advanced prostate cancers did substantially worse than old men with similar forms of the disease," said Dr. Daniel W. Lin, lead author of a report in the July 1 issue of Cancer. "Among men with high-grade and high-stage prostate cancers, younger men are approximately three times more likely to die of prostate cancer than all other age groups."

The finding comes from an analysis of outcomes of 318,774 men listed in a national database of prostate cancer whose diagnosis was made between 1988 and 2003. That analysis also showed that over time, more American men are being diagnosed with prostate cancer at an earlier age, likely because of more intensive screening programs.

The study results add more doubts about the value of such screening programs, said Dr. Otis W. Brawley, chief medical officer of the American Cancer Society. "Men with high-grade tumors are less likely to benefit from screening," Brawley said.

But the results drew exactly the opposite reaction from Dr. Stephen Freedland, an associate professor of urology and pathology at Duke University. "Really young men, those 35 to 44, have worse cancers," Freedland said. "This is not a group of men where we typically screen for prostate cancer. The percentage of metastatic disease is higher than for any other group. This is a failure of early diagnosis."

The finding thus lends support to the recent recommendation by the American Urological Association that men should have a first screening test for prostate-specific antigen (PSA) at age 40, Freedland said.
The lessons Lin, who is chief of urologic oncology at the University of Washington, drew from the study were not primarily about screening. "This might give some insight into prostate cancer in younger men," Lin said. "We could identify high-risk cases earlier, and thus enroll those men into clinical trials. With current treatment options limited, this is a call in part for considering clinical trials and ongoing studies of new treatments."

So for physicians treating prostate cancer, "our message is that younger men with high-grade cancers do very poorly, and when you find one, be aware that it should be treated aggressively and with experimental methods if necessary," Lin said.

PSA screening is now a major issue, with a controversy triggered by two recent reports indicating that routine screening is relatively ineffective at reducing prostate cancer deaths.

Screening recommendations by major organizations vary widely, Brawley noted, with some groups, including the American Association of Family Physicians, flatly against such programs. The American Cancer Society guidelines, which now are under review, call for a physician to discuss, but not necessarily offer, a PSA test to men with normal risk at age 50, and to high-risk men at 45.

Men at higher risk are those with a father or brother who has had the disease, and black men, who are more likely to develop prostate cancer for unknown reasons, Brawley said.

The new study supports the recommendation for earlier screening, Freedland said. "These are men that have 30 to 40 years to live, and will have the most benefit from screening," he said.

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