March 09 Newsletter Articles

Selenium, Vitamin E Don’t Help After All

Do vitamin E and selenium help prevent prostate cancer? The answer is no, according to findings from a major trial with 35,000 men. The SELECT study, sponsored by the National Cancer Institute and begun in 2001, was stopped early, in September, after finding no evidence of any benefit from either supplement.

The news disappointed many cancer experts, says Elise Cook, M.D., a study researcher and a cancer prevention specialist at M.D. Anderson Cancer Center in Houston. But it provides important information about what doesn’t work. Cook says many men had been reluctant to join the study because they were already taking vitamin E for heart as well as prostate health. “Since then, other studies have shown that it really didn’t help their hearts, either,” she says.

Catharine Greider

STUDY REVEALS WHY OBESE MEN HAVE LOWER PSA READINGS

North American researchers conducting a retrospective multi-institution study have found what they consider the likely explanation for two anomalies: (1) the common observation that men with a higher body mass index (BMI) tend to have lower prostate specific antigen (PSA) readings; and (2) recent results linking obesity with more aggressive prostate disease.

New results conclude that the critical factor is "hemodilution" - a phenomena where the greater volume of blood in bigger men lowers PSA readings by diluting the concentration of the PSA protein, which is believed to enter the bloodstream when the prostate enlarges.

Though the findings need to be confirmed in prospective studies, the researchers believe that hemodilutiori could also compromise evaluation of other circulating disease markers in high-BMI patients.

More than 13,600 patients had radical prostatectomies at Duke Prostate Center, Johns Hopkins Hospital, or 5 Veterans Administration medical centers between 1988 and 2006. All had reliable measurements taken of their BMI and PSA. Using statistical methods, researchers were able to calculate how much blood each patient had, how much actual PSA protein (mass) was present, and thus the PSA concentration. Men with a BMI over 35 (30 and above is obese) had 21-23 percent more blood and 11-21 percent lower PSA concentrations than men of normal weight, without, in most cases, statistically significant increases in the mass of circulating PSA protein.

The work was published in the November 21st issue of the Journal of the American Medical Association by Dr. Stephen Freedland of Duke University Medical Center and colleagues from more than a dozen participating centers and institutions. "For these other tests [looking for biomarkers of cancer and other diseases] just starting down the pipeline," he says, "we need to think of the total amount of a biological marker rather than concentration."

NCI Cancer Bulletin, 4 December 2007

RADIATION ADDED TO ANDROGEN DEPRIVATION THERAPY HALVES RISK OF PROSTATE CANCER DEATH

Adding radiation therapy (RT) to androgen deprivation therapy (ADT) in older men with locally advanced prostate cancer reduces the risk of dying from the disease by half. These results, from a randomized clinical trial, suggest that men should be offered this additional option, says lead researcher Anders Widmark, MD, professor in RT oncology at Umea University in Umea, Sweden. Dr. Widinark presented the results at a plenary session during the American Society for Therapeutic Radiology and Oncology (ASTRO) 50th Annual Meeting in Boston, Massachusetts.

The trial involved 880 patients, median age 67 years, the majority of whom had stage T3 disease. All of the patients underwent 3 months of intense ADT to achieve total androgen blockade, followed by continuous ADT, but one group also received RT.

After a median follow-up of 7.5 years, death from prostate cancer had occurred in 79 (18%) of 437 patients in the ADT group vs 37 (8.5%) of 436 patients in the combined ADT and RT group. "It was rather surprising that the addition of RT cut by half the risk of death from prostate cancer," Dr. Widmark commented. The absolute cumulative difference in the prostate cancer death rate increased from 2.9% at 7 years to 12% at 10 years, with a relative risk of 0.44 (P 0.00003).

In addition, significant reductions were seen in two other outcome measures. Overall mortality rate was 30% in the ADT group vs 21.6% in the ADT+RT group (P = 0.004). Plus, recurrence of high levels of serum PSA occurred in 65% of the ADT group but in only 17.5% in the ADT+RT group (P= 0.00001).

Quality of life, as reported both by patients and by clinicians, was "slightly worse" in patients who received ADT+RT vs those in the ADT group but "only marginally," Dr. Widmark commented. Adverse events included moderate to severe urinary leakage (reported by 6% of patients in the ADT+RT group vs 3% in the ADT group 4 years after treatment) and pain on urination (reported by 2% vs 4%, respectively). Erectile dysfunction was also more common, reported by 85% of patients in the ADT+RT group vs 72% in the ADT group (P < .001).

"This trial will change clinical practice," predicted Anthony Zietman from Massachusetts General Hospital in Boston, who was moderating a press briefing at which the results were highlighted. "At present, there is a bit of a fatalistic attitude towards locally advanced prostate cancer, as it generally considered to have already quietly spread elsewhere," Dr. Zietman commented. "Often the only treatment often offered to older men with this stage of disease is ADT," he continued. "The thinking is that the cat is already out of the bag... but "the results from this trial prove that this is not the case."

"This randomised trial is the first to show that men with locally advanced prostate cancer will survive substantially longer when RT is added to their treatment plan," Dr. Widmark told journalists. "Considering the substantial survival benefit, the increase in symptoms seems to be acceptable and of small influence on quality of life 4 years after treatment," he concluded. Presented at ASTRO's 50th Annual Meeting, plenary session, 22 September 2008

Medscape, 23 September 2008