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PROSTATE CANCER NEWSLETTER - April 2009

New guidelines on prostate cancer screening suggest that annual PSA blood tests might not be necessary for many men, but the same guidelines call for a "baseline" PSA test at the age of 40, rather than 50.

A prostate-specific antigen (PSA) test to detect early signs of prostate cancer should be
offered to "well-informed men aged 40 and older who have a life expectancy of
10 years," state clinical guidelines issued Monday by the American Urological Association
at its annual meeting in Chicago.

Noting that the issue of PSA testing and how it should be used to guide treatment
"is highly controversial," the association still stated that the test, "when offered
and interpreted appropriately, may provide important information for the diagnosis,
pre-treatment staging or risk assessment or post-treatment monitoring of prostate cancer."

But it's important that "the risks and benefits of PSA screening be discussed with men before
the test is done," said Dr. Peter Carroll, chairman of the department of urology at the
University of California, San Francisco, who headed the committee that drew up the new guidelines.

Those risks can include impotence and incontinence caused by unnecessary surgery.

The recommendation that a first PSA test be offered to men at 40 should help doctors spot high-risk patients more readily, however. "PSA at that age is strongly predictive of the future risk of prostate cancer," Carroll said. "Later detection in the 50s, when the cancer would be more advanced, could be avoided."

The guidelines also recognize that many prostate cancers grow so slowly that they are of no risk, he said. Further steps after detection of an elevated level of PSA, a protein produced by the prostate, should require consideration of "other risk factors, such as family history and ethnicity," Carroll said.

Another major change is that the guidelines set no specific PSA blood level as an indicator of danger, he said. The danger level for an individual man will depend on other risk factors.

And yearly PSA tests might not be needed for many men, the guidelines note. "Screening less frequently may be a less costly way to screen," Carroll said. No specific timetable for less frequent screening is set in the guidelines, but they might be recommended as more information becomes available, he said.

The new guidelines did take into account two recent studies, one in Europe which found that regular PSA screening reduced prostate cancer deaths, and one in the United States which found no effect of screening, Carroll said. The U.S. study was flawed in several ways, he noted. For example, it permitted men who were not assigned to the group for screening to go have PSA tests on their own.

"Both studies do not suggest that PSA screening should not be undertaken," Carroll said.

New information on PSA testing has been a major focus at this year's AUA meeting. One study by urologists at the University of Colorado focused on the timing of PSA tests. The study, which followed more than 76,000 men for at least five years, found that the PSA levels of nearly 99 percent of men with very low readings on an initial test would remain low for at least five years. That suggests that limiting tests to every five years for men at that low level, and to every two years for men with slightly higher readings, would lower the overall need for PSA tests by 70 percent, reducing testing costs by $1 billion a year, the researchers reported.

On the other hand, a Swedish study found that PSA readings at age 60 were strong indicators of increased prostate cancer death risk. But "60 -year-old men with PSA at or below 1 nanogram per milliliter [a low reading] can be told that although they harbor prostate cancer, it is very unlikely to become life-threatening," the researchers wrote.

A third report at the meeting took issue with the recommendation of the U.S. Preventive Task Force that men aged 75 and older should not have PSA tests at all.

Dr. Judd W. Moul said that when he read that recommendation, he did a poll of 340 older men at the Duke University Prostate Center, which he heads. "My immediate reaction was that it was age discrimination," he said.

The survey, done by Duke medical students, found that 78.2 percent of the men were upset by the recommendation, said Moul, an outspoken proponent of PSA testing.

Moul acknowledged that the report had been refused publication by a medical journal on the grounds that it was biased. But he said the advice to stop PSA testing after 75 "was supported neither by public opinion nor by our outcomes data."

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Heart, Bone Problems May Follow Prostate Cancer Treatment

Though proven effective, treating prostate cancer with the testosterone-lowering treatment known as androgen deprivation therapy may raise men's risk for developing bone fractures and fatal cardiovascular disease, a new study suggests.

The likelihood of developing either side effect remains low, the researchers noted. But the study shines fresh light on the question of how best to weigh the potential benefits of androgen deprivation therapy (ADT) against the potentially serious complications that can ensue.

"It is important to point out that these adverse outcomes due to ADT are all preventable, so it's up to a patient's doctor to be vigilant of changes in either cardiovascular or skeletal health that might develop as a result of the therapy," said the study's lead author, Lockwood Taylor, a doctoral candidate in the division of epidemiology and disease control at the University of Texas Health Science Center in Houston.

The findings will appear in the June 1 issue of Cancer.

To assess side effects from ADT, Taylor and his colleagues reviewed 14 studies from 1966 to 2008 that focused on skeletal and cardiovascular side effects linked to ADT among men battling prostate cancer.

They found that ADT boosted the risk for overall fracture by 23 percent relative to men with prostate cancer not undergoing treatment.

Similarly, the chances of dying from heart disease were 17 percent higher among men with cancer on ADT than those not on ADT.

They also pointed to two large studies that had indicated a substantial increase in the risk for developing diabetes among ADT patients.

"It would certainly be important to point out that, although we observed some statistically significant increases in the relative risk for these side effects, the absolute risks are still very low," Taylor stressed.

"But I would say that doctors should certainly monitor their patients on ADT for changes in bone mineral density, and, if they see a decrease, then they should consider some preventive therapies," he advised. "They should also be vigilant for abnormal lipo [blood fat] profiles, in terms of cholesterol levels and serum levels of insulin, which are markers for both cardiovascular and skeletal fracture."

He said that doctors could prescribe statin drugs to help lower cholesterol, while encouraging lifestyle changes to improve diet and physical activity.

Dr. Nelson Neal Stone, a clinical professor of urology and radiation oncology at the Mount Sinai School of Medicine in New York City, said that the findings "reinforce what we already know".

"It's been well known for a while that ADT boosts a patient's risk for fracture, just like it happens among women who go on anti-estrogen therapy for breast cancer," Stone noted. "And there have been several studies published in the last three to five years that find that men who go on the therapy are at an increased risk for all sorts of cardiovascular issues."

"While we all know that this therapy is needed to prevent the progression of metastases, it is true that while you are preventing a serious event on the one hand you are potentially putting the patient at risk," Stone said.

"So the bottom-line is that we have to be careful about who we put on ADT," he said. And research into preventive techniques needs to continue, he said, "because the therapy obviously entails some potentially severe side effects."

Several new studies suggest statins help prevent prostate cancer and reduce the risk of erectile dysfunction.

"At this point in time, there seems to be mounting evidence that there may be a future role for statins in prostate cancer treatment or prostate cancer prevention," said Dr. Lionel L. Banez, from the Division of Urologic Surgery and Duke Prostate Center at Duke University Medical Center and lead author of one study. "There will definitely be more men taking statins for cardiovascular reasons, and this is a great opportunity for us to see how many of these men develop prostate cancer and whether these prostate cancers are aggressive."

All the reports were to be presented Sunday at the American Urological Association's annual meeting, in Chicago.

One study found that men who were taking statins before undergoing surgical removal of their prostate had a lower risk of having the cancer return. "The use of statins at the time of surgery was associated with a 30 percent reduction in the risk of recurrence of prostate cancer," said lead researcher Dr. Robert J. Hamilton, a urology resident at the University of Toronto Medical Center in Ontario, Canada.

Hamilton thinks that the anti-inflammatory properties of statins may explain the finding. However, it might also be the ability of these drugs to lower cholesterol that has an effect on cancer cells, he said.

Although these results are promising, Hamilton is cautious about recommending that men should take statins to reduce the risk of recurrent prostate cancer. "At this point, we cannot with confidence say that that's true," he stressed.

There are also several unanswered questions, including the optimal dose, the length of time one needs to be taking statins to achieve a benefit, and whether starting statin therapy after surgery would have the same effect.

"Although the results of these studies are exciting, they need to be confirmed," he said.

Another study focused on inflammation inside prostate cancer tumors. "We looked at the association between statin use and prostate tumor inflammation," Banez said.

"We found that men who were using statins prior to surgery had a significantly lower risk for inflammation within their prostate tumor," Banez said.

In fact, men taking statins had a 72 percent reduction in the risk for inflammation of the prostate tumor. The researchers also found that obesity appears to be associated with increased inflammation and more aggressive prostate cancer.

In a third report, researchers led by Dr. Stacy Loeb, from Johns Hopkins University, found statins may help in reducing the aggressiveness of prostate cancer. "Our results suggest that the use of statins may be associated with more favorable pathological features at radical prostatectomy," the researchers said in a statement.

In a fourth report, researchers led by Dr. Rodney H. Breau from the Mayo Clinic found that statins were associated with a lower risk of developing prostate cancer. Among 75 men taking statins who had biopsies, 30 tested positive for prostate cancer, the researchers found.

"In recent years, it has been suggested that statin medications may prevent development of cancer. However, until now, there has been limited evidence to support this theory," Breau said in a statement. "Our research provides evidence that statin use is associated with a threefold reduced risk of being diagnosed with prostate cancer."

There may come a time when people will be taking statins to treat or prevent prostate cancer, Hamilton noted. "If these studies keep rolling in suggesting that there is something there with prostate cancer, then the use of statins could go up," he said.

In a fifth study, Mayo Clinic researchers found that statins and/or with non-steroidal anti-inflammatory drugs (NSAIDs) resulted in fewer lower urinary tract symptoms related to an enlarged prostate.

The researchers found that statin users were 63 percent less likely to develop lower urinary tract problems and 57 percent less likely to develop an enlarged prostate.

"Statins have been shown to have anti-inflammatory effects, and previous research suggests inflammation may be associated with benign prostate disease," lead researcher Dr. Jennifer L. St. Sauver said in a statement. "This study suggests that men's urinary health could be improved by taking statin medications."

In another report from Mayo Clinic researchers, older men taking statins over an extended period had a lower risk of developing erectile dysfunction (ED).

Statins were associated with a decreased risk of ED among men older than 60. Moreover, men who took statins for a longer time were less likely to develop ED. For example, men taking statins for nine years or more were 64 percent less likely to develop ED. Men who took statins for less than three years had about the same risk of developing ED as men who did not take statins, the researchers found.

"Protection of vascular health remains an important concomitant of preserving erectile health. Our data suggest that longer use of statins may result in the lowest risk of erectile dysfunction," study author Dr. Ajay Nehra said in a statement.

Stress Management Battles Prostate Cancer Anxiety
Brief counseling before, after surgery eases concern over side effects, study finds .

Stress management counseling appears to benefit men who have all or part of their prostate removed (radical prostatectomy) to treat early-stage prostate cancer, says a U.S. study.

The study included 159 patients who were assigned to receive one of the following: two 60- to 90-minute sessions of pre-surgical stress management counseling and brief booster sessions the morning of, and 48 hours following surgery; two 60- to 90-minute sessions of individual supportive attention sessions and boosters similar to the stress management group; or standard care (no therapy).

In the short term (one week before and the morning of surgery), men in the stress management group had the lowest levels of mood disturbance (distress, anxiety, depression), followed by those in the supportive attention group. There was a statistically significant difference between men in the stress management group and those in the standard care group, who had the highest levels of mood disturbance.

In the long term (six weeks and 12 months after surgery), the men in the stress management group reported the highest levels of physical functioning and aspects of quality of life. Again, the difference between the men in the stress management group and those in the standard care group was statistically significant.

The study was published in April in the Journal of Clinical Oncology.

"We know that for men with early-stage prostate cancer, the time when they are making treatment decisions is very stressful. A radical prostatectomy is not without possible, very personal, consequences, including urinary incontinence and erectile dysfunction. Patients may also be worried about the uncertainty that the surgery will cure their cancer," senior author Lorenzo Cohen, a professor in the departments of behavioral science and general oncology at the University of Texas M.D. Anderson Cancer Center, said in a news release.

"Before we can suggest that stress management is useful prior to surgery for all men undergoing a radical prostatectomy, we need to better understand the mechanism behind our findings, as well as understand for whom this type of intervention will be the most useful," Cohen noted. "However, that said, all diagnosed with cancer treatment should be encouraged to participate in any stress management program -- be it mind-body, or cognitive in nature. We know that they are safe and may improve patients' well-being and help them adjust to a cancer diagnosis."

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