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PROSTATE CANCER NEWSLETTER - February 2009

Men with highest ionized serum calcium 3 times more likely to die, study finds.

A newly identified biomarker for fatal prostate cancer may help guide men trying to decide whether or not to undergo treatment for the disease.

Men whose levels of ionized serum calcium are in the highest third are three times more likely to die of prostate cancer than those with the lowest levels, said researchers at Wake Forest University School of Medicine and the University of Wisconsin. They also confirmed a previous finding that men with the highest levels of total serum calcium are twice as likely to develop fatal prostate cancer.

The study, published in the February issue of the journal Cancer Epidemiology, Biomarkers & Prevention, is the first to examine the link between fatal prostate cancer risk and pre-diagnosis levels of ionized serum calcium.

The findings highlight the need for more research into the link between calcium and prostate cancer and may also help patients make treatment decisions, the researchers said.

"Many men with this diagnosis are treated unnecessarily," senior author Gary G. Schwartz, an associate professor of cancer biology at Wake Forest University Baptist Medical Center's School of Medicine, said in a university news release.

"Within months of initial diagnosis of prostate cancer, many men opt to undergo either radiation or radical surgery. The problem is, we don't know who needs to be treated and who doesn't, so we treat most men, over-treating the majority," Schwartz explained. "These new findings, if confirmed, suggest that men in the lower and of the normal distribution of ionized serum calcium are three times less likely than men in the upper distribution to develop fatal disease. These men may choose to delay treatment or perhaps defer it altogether."

The findings also suggest "that medicines may be able to help in lowering the risk of fatal prostate cancer by reducing serum calcium levels," he added.

Schwartz noted that diet has little effect on serum calcium levels, which are controlled genetically and are stable over much of a person's life. "These results do not imply that men need to quit drinking milk or avoid calcium in their diets," he said.

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Few major complications after prostate radiation

Less than 7 percent of men with prostate cancer who have radiation therapy experience major complications in the first 30 days, new research shows.

Radiation therapy "is quite safe for older patients, although it is associated with a small but measurable increase in short-term major complications," Dr. Shabbir M. H. Alibhai from University Health Network, Toronto, Ontario, Canada told Reuters Health.

Alibhai and colleagues compared major 30-day complications in men who had radiation therapy or radical prostatectomy (removal of the prostate) for early "organ-confined" prostate cancer.

Despite being older and having more co-existing illnesses, men who received radiation had lower complication rates in each category compared with men who had surgery, the investigators found.

Among the 7,661 men who received radiation, 9 (0.1 percent) died within 30 days. The 30-day mortality rate increased with age (from 0 percent for men younger than 60 years to 0.8 percent for men aged 80 years and older). Among the 11,010 men who had surgery, 53 (0.5 percent) died within 30 days.

Only 6.5 percent of men had at least 1 complication within 30 days of radiation, the researchers note, compared to 30.2 percent of surgery patients.

In the radiation group, complication rates peaked within 30 days and then declined promptly, for every category of complications.

"Our data confirm the belief that most prostate cancer specialists have about the relative safety of (radiation therapy) in older men," Alibhai concluded. "We recognize this is only one part of a triangle, the other points being long-term efficacy and long-term toxicity (particularly genitourinary, sexual, and gastrointestinal) that must be considered when deciding on an active treatment (i.e., radical prostatectomy or radiation therapy) for early-stage prostate cancer."

A simple urine test that identifies small molecules, called metabolites, that are associated with prostate cancer might someday be able to identify men who have a fast-moving, aggressive form of the disease, University of Michigan researchers report.

They say such a test could help identify those who need aggressive treatment and might one day lead to the development of new therapies.

"There are metabolites that might be useful in predicting aggressiveness of prostate cancer," said lead researcher Dr. Arul Chinnaiyan, director of the Michigan Center for Translational Pathology and a professor of pathology and urology.

"Metabolites, similar to genes and proteins, should also be measured in understanding cancer," he said. "They have been under-appreciated relative to genes being profiled in cancer. This approach could be extended to other cancers."

However, before a urine test involving metabolites could become standard medical practice, it would have to be tested in animals and then in people through clinical trials, Chinnaiyan said.

The findings were expected to be published in the Feb. 12 issue of Nature.

For the study, Chinnaiyan's group analyzed 1,126 metabolites from 262 tissue, blood and urine samples taken from men with early, advanced and metastatic prostate cancer. From these samples, the researchers identified 10 metabolites that frequently appeared with prostate cancer and especially with advanced prostate cancer.

One of the 10 metabolites, called sarcosine, was the most indicative of advanced prostate cancer, the researchers found. Sarcosine levels were elevated in 79 percent of the samples from men with metastatic cancer (cancer that has spread) and in 42 percent of the samples from men with early stage disease, the researchers found.

No trace of sarcosine was found in samples from men who did not have prostate cancer, the researchers noted.

According to the report, sarcosine was a better indicator of advanced prostate cancer than the current marker for the disease, prostate specific antigen (PSA).

And, sarcosine's involvement in the invasiveness of the cancer suggests that blocking it might be a target for future drug development, Chinnaiyan said.

The findings are preliminary, though, Chinnaiyan noted, and it would be years before a test or treatment based on the metabolite could be available. Ideally, he said, researchers would like to find other metabolites associated with prostate cancer that would help predict the course of the disease with even more precision.

More than 186,000 people in the United States will be diagnosed this year with prostate cancer, and almost 29,000 will die from the disease, according to the American Cancer Society.

Michael M. Shen, a professor of medicine, genetics and development at Columbia University College of Physicians and Surgeons in New York City, and co-author of an accompanying journal article, said that the report advances the use of metabolites in understanding cancer.

"The hope is that this approach will ultimately yield a clinical application," Shen said. "For example, one could screen urine from men and not only diagnose prostate cancer but have information that would be useful for cancer prognosis."

However, that goal is a long way off, he said. "The importance of the paper is that there is a new methodology that has not been pursued extensively before, which in combination with existing approaches may yield advances in cancer diagnosis and prognosis," he said.

Dr. Margaret K. Offermann, the deputy national vice president for research at the American Cancer Society, stressed that studies are needed to see if the approach could be used in patients.

"This is not a perfect test," Offermann said. "It is not perfectively predictive of when someone is going to have prostate cancer and when that cancer is going to misbehave, but it may help in combination with PSA," she said.

And it could be a new target for treatment, she said. "Potentially, by blocking the formation of sarcosine or related compounds, it may actually help in the treatment," she explained.

Prostate cancer may cause neglect of other illness.

The majority of men with early-stage. low- or moderate-grade prostate cancer die from causes other than prostate cancer, researchers report in the Journal of the American Geriatric Society. Therefore, prevention and management of other health conditions is important in these patients.

"Once a diagnosis of cancer has been made, it can become the sole focus of medical care," Dr. James S. Goodwin and colleagues write. "This is understandable, because cancer is typically life threatening and often requires dramatic therapy. But earlier cancer diagnoses, due to screening, and improvements in treatment have been associated with lower cancer mortality," they note.

"Thus, patients are living longer after a diagnosis of cancer," to the point where other illness may have a substantial effect on their survival, they point out.

Goodwin, of the University of Texas Medical Branch, Galveston, and colleagues used data from the Surveillance, Epidemiology, and End Results (SEER) Medicare database to assess the outcome of 208,601 men between the ages of 65 and 84 years diagnosed with prostate cancer from 1988 through 2002. Overall, 59.1 percent of the entire group had early-stage prostate cancer with low- to moderate-grade tumors.

The mortality in these patients was similar to that of men the same age without prostate cancer. Among the men with early-stage, low- or moderate-grade tumors, mortality from prostate cancer was 2.1 percent versus 6.4 percent from heart disease, and 3.8 percent from other cancers.

The "substantial effect" of other illnesses on survival and the high mortality rate from causes other than prostate cancer may have important implications, Goodwin's team notes.

Treatment decisions for localized prostate cancer should consider life expectancy based on age and the contribution of other conditions to the patient's mortality, they note. Also, the decision to use androgen deprivation therapy, which is now commonly used to treat even early-stage prostate cancer, must be made carefully if another significant illness is present. With this approach, androgen, a male sex hormone that can stimulate the growth of prostate cancer tumors, is blocked.

Overall, the team concludes that older men with early-stage prostate cancer "would be well served by an ongoing focus on screening and prevention of cardiovascular disease and other cancers."