What would happen without PSA testing?

Eliminating the PSA test to screen for prostate cancer would be taking a big step backwards and would likely result in rising numbers of men with metastatic cancer at the time of diagnosis, predicted a University of Rochester Medical Center analysis published in the journal, Cancer.

01 aug 2012--The URMC study suggests that the prostate-specific antigen (PSA) test and early detection may prevent up to 17,000 cases of metastatic prostate cancer a year. Data shows, in fact, that if age-specific pre-PSA era incidence rates were to occur in the present day, the number of men whose cancer had already spread at diagnosis would be three times greater.

"Our findings are very important in light of the recent controversy over PSA testing," said Edward M. Messing, M.D., study co-author, chair of Urology at URMC, and president of the Society of Urologic Oncology. "Yes, there are trade-offs associated with the PSA test and many factors influence the disease outcome. And yet our data are very clear: not doing the PSA test will result in many men presenting with far more advanced prostate cancer. And almost all men with metastasis at diagnosis will die from prostate cancer."

Prostate cancer usually occurs in older men, and is the second leading cause of cancer death in the male population. In 2012 an estimated 241,740 new cases will be diagnosed and 28,000 deaths will occur. Prognosis depends on whether the cancer has spread outside the prostate gland, and the degree to which the cancer cells are abnormal.

In 2011 the U.S. Preventative Services Task Force recommended against PSA screening in all men, prompting criticism from the medical community. The government panel reviewed scientific evidence and concluded that screening has little or no benefit, or that the harms of early detection outweigh the benefits. One major concern, for example, was that doctors are screening for, finding, and treating non-aggressive cancers that might have remained quiet, causing patients to needlessly suffer from serious treatment side effects such as incontinence or erectile dysfunction.

The U.S. Task Force recommendations against screening caused some confusion, and in response, a special panel of experts from the American Society of Clinical Oncology this month issued its own opinion. The ASCO panel decided that for men with a life expectancy of less than 10 years, general screening with the PSA test should be discouraged. For men with a longer life expectancy, though, it is recommended that physicians discuss with patients whether the PSA test is appropriate for them.

Messing's study looked back at the era prior to 1986, when no one was routinely screened for prostate cancer with a PSA test. To analyze the effect of screening on stage of disease at initial diagnosis, Messing and Emelian Scosyrev, Ph.D., assistant professor of Urology, reviewed data from 1983 to 2008 kept by the nation's largest cancer registry, Surveillance, Epidemiology and End-Results or SEER. They compared SEER data from the pre-PSA era (1983 to '85) to the current era of widespread PSA use (2006 to 2008), and adjusted for age, race, and geographic variations in the United States population.

Approximately 8,000 cases of prostate cancer with metastases at initial presentation occurred in the U.S. in 2008. Using a mathematical model to estimate the number of metastatic cases that would be expected to occur in 2008 in the absence of PSA screening, Scosyrev and Messing predicted the number would be 25,000.

The authors emphasized the study was observational and has some limitations. In particular it is impossible to know if the PSA test and early detection is solely responsible for the fewer cases of metastasis at diagnosis in 2008.

The potential lead-time of screening also should be considered when interpreting the study findings, Scosyrev said. For some people an earlier stage of cancer at diagnosis may not always translate into better survival. This may happen, for example, in cases when the cancer had already metastasized at the time of screening, but the metastasis remained undetected.

In general, however, the study concluded that massive screening and PSA awareness efforts during the 1990s and early 2000s resulted in substantial shifts toward earlier-stage disease and fewer cases of metastases at diagnosis.

In the United States over the most recent 20 years, Messing said, prostate cancer death rates have been reduced by close to 40%. This occurred without substantial changes in how men were treated (via surgery and radiation therapy). Other models published in the scientific literature have suggested that more than 50% of this reduction is due to early detection.

More information: “Prostate-specific antigen screening for prostate cancer and the risk of overt metastatic disease at presentation: analysis of trends over time.” Emil Scosyrev, Guan Wu, Supriya Mohile, and Edward Messing. CANCER; Published Online: July 30, 2012 (DOI: 10.1002/cncr.27503).

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More Research Finds Limited Benefit From PSA Test

Also, many men not fully sharing in decision with provider whether to undergo testing

01 oct 2009-- Men should be aware of their chances of benefits and harms from prostate-specific antigen (PSA) testing before the test, but many are not discussing screening before making the decision, according to the results of two studies in the Sept. 28 Archives of Internal Medicine.

Kirsten Howard, Ph.D., of the University of Sydney in Australia, and colleagues analyzed data from a model comparing outcomes from prostate cancer in men with and without annual screening. The authors presumed a 20-percent relative risk reduction in prostate cancer mortality in screened men as a best case. If 1,000 men were screened from ages 40 to 69, they would have 27.9 prostate cancer deaths and 639.5 deaths overall by age 85, compared with 29.9 prostate cancer deaths and 640.4 deaths overall in their unscreened counterparts. False alarms were a concern, along with the attendant risks of biopsies triggered by the screening.

Richard M. Hoffman, M.D., of the New Mexico VA Health Care System in Albuquerque, and colleagues analyzed data from 375 men, ages 40 and older, who had undergone or discussed PSA testing with their health care provider in the previous two years. Only 69.9 percent discussed screening before making a decision. The provider was more likely to raise the idea and was more likely to emphasize benefits of testing than shortcomings (71.4 versus 32 percent).

"Even if there is a small expected benefit from screening under optimistic assumptions, it is unlikely that screening represents a good value for the expenditure of resources based on the potential cost per quality-adjusted life-year gained," writes the author of an accompanying editorial.

Several authors of the second study reported financial associations with the Foundation for Informed Medical Decision Making, which supported the study.

Abstract - Howard
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Abstract - Hoffman
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Men who take aspirin have significantly lower PSA levels

WASHINGTON, D.C., 18 nov 2008 - The use of aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) is significantly associated with lower PSA levels, especially among men with prostate cancer, say researchers at Vanderbilt University.

This large analysis known as the Nashville Men's Health Study included 1,277 participants referred to a urologist for a biopsy of their prostate. Approximately 46 percent of the men reported taking an NSAID, mostly aspirin (37 percent of all men). After adjusting for age, race, family prostate cancer history, obesity, and other variables that have independent effects on the size of the prostate organ, cancer risk, and PSA levels, the researchers found that aspirin use was significantly associated with lower PSA levels. PSA levels were 9 percent lower in men taking aspirin (the NSAID most commonly used) compared with men who did not use aspirin, say the researchers, who will present their findings at the American Association for Cancer Research's Seventh Annual International Conference on Frontiers in Cancer Prevention Research.

A PSA test is used widely as a method to screen men for the possibility of prostate cancer, with higher blood PSA levels suggesting a greater chance of having prostate cancer. High PSA levels can also signify benign prostatic hyperplasia (BPH), a non-cancerous enlargement of the prostate organ.

"To begin to understand how aspirin may lower PSA, we also looked at the association between NSAID use and prostate volume," said the study's lead investigator Jay H. Fowke, Ph.D., an assistant professor in medicine at Vanderbilt. "Aspirin users and men who didn't use aspirin had the same prostate volume, so I don't think aspirin was changing PSA by changing the prostate volume. It was doing something different, and that suggests a beneficial effect on cancer development."

Furthermore, "the effect of aspirin on PSA was only somewhat evident among men without prostate cancer but was strongest in men later found to have prostate cancer. This also suggests an effect on cancer as opposed to other prostate diseases."

"There are several ways to consider the impact of these results," said Dr. Fowke.

"Several prior studies reported anti-inflammatory drugs like NSAIDs were associated with lower prostate cancer risk. Our data also suggest that NSAID use has a beneficial effect on prostate cancer. These findings could be consistent with a protective effect, because aspirin reduced PSA levels more among those men who were diagnosed with prostate cancer than among men with other prostate diseases."

However, these data also indicate that NSAID use could affect our ability to detect prostate cancer, regardless of any reduction in prostate cancer risk. "This analysis raises the concern that aspirin and other NSAIDs may lower PSA levels below the level of clinical suspicion without having any effect on prostate cancer development, and if that is true, use of these agents could be hampering our ability to detect early-stage prostate cancer through PSA screening," Fowke said.

It is also possible that results from prior studies suggesting that NSAID use reduced prostate cancer risk may just be picking up a reduced ability to detect prostate cancer among NSAID users.

These results are consistent with a recent survey of healthy men from the general population, and future studies will need to find a way to determine if NSAID use is affecting prostate cancer risk or our simply our ability to detect prostate cancer.

"It will be important to understand which mechanism is in play because many men take NSAIDs for their cardiovascular health, so we need to know whether that reduces their prostate cancer risk, or simply reduces PSA, which would then be even less reliable as a marker of prostate cancer risk," he said. "Basing treatment on an artificially suppressed PSA score would also be problematic."

PSA Test Still Important to Detect Prostate Cancer, Studies Find

Despite questions as to whether early screening for prostate cancer is accurate, new research suggests it continues to be important.
And even more encouraging news indicates that statins, drugs designed to lower cholesterol, might also reduce the risk of developing prostate cancer. Both sets of findings were presented Sunday at the American Urological Association's annual meeting, in Anaheim, Calif.
Screening for prostate cancer has become controversial, particularly the issue of whether a prostate-specific antigen (PSA) blood test is useful as an early detector of malignancy. Two studies presented at the conference indicate it is still worthwhile to have such a test.
In one study, Dr. Hans Lilja, from Memorial Sloan-Kettering Cancer Center in New York City, and colleagues found that PSA testing of men in their 40s was predictive of developing prostate cancer later. In fact, the higher the initial PSA, the greater was the probability that the cancer would be aggressive, the research showed.
As recently as last month, a study published in the Journal of the National Cancer Institute found that PSA tests "perform poorly in distinguishing between those who develop a lethal prostate cancer from those at low or no risk of disease progression."
But among the patients in the Sloan-Kettering study, risk for prostate cancer was concentrated, with 89 percent of advanced cancers occurring in men with the top 10 percent of PSA levels, the researchers found.
Lilij thinks that men should have an initial PSA test when they are in their 40s rather than waiting. "It is surprising that this marker can predict cancer 20 years later," he said. "We should focus our efforts on those men who are on the highest risk for cancer."
Another study found that among patients who had a radical prostatectomy (removal of the prostate and some of the tissue surrounding it), those who had been screened for prostate cancer were more likely to have malignancy confined to the prostate, compared with men who had not been screened.
"Patients should be screened," said lead researcher Dr. Alexandre E. Pelzer, from the Medical University Innsbruck, Austria. "Screening reduces mortality from prostate cancer by 50 percent in our part of Austria, where screening is done, compared with other parts of the country where it isn't," he said.
Another debate in prostate cancer care is whether patients diagnosed with the disease should be treated immediately or whether watchful waiting is best.
In one study, Dr. Marc A. Dall'Era, and colleagues from the University of California, San Francisco, found that it was not possible to predict how fast the cancer would progress among the study subjects who had what was termed low-risk prostate cancer.
In the study, more than 400 men had their cancer watched monthly. "Among the men on active surveillance, about 28 percent progressed," Dall'Era said. "Over five years, none of the men died from prostate cancer," he added.
Men who opted for treatment were those who had the highest grade tumors, Dall'Era added.
In another study, Dr. Bradley A. Erickson, from Northwestern University, and colleagues collected data on 347 older men who selected watchful waiting. Among these men, 36 percent showed progression and/or underwent secondary treatment. Overall mortality was 30 percent, with 8 percent dying from prostate cancer.
"Men who were more likely to die were those with higher PSA and those whose cancer progressed," Erickson said. "This is the first study to that gives us a natural history of PSA screening."
In a second group of studies, researchers presented evidence that statins might reduce prostate cancer risk.
In the first report, Dr. Janet Colli, and colleagues from the University of Alabama, Birmingham, were able to make an association between declining prostate cancer rates in the United States and statin use.
The researchers said they found the declining death rates were most noticeable among white men who used statins. "There was a very strong correlation between declining prostate cancer mortality rates and declining high cholesterol levels in white males," Colli said.
Colli thinks statin use may be one reason for this decline in prostate cancer mortality. "Future studies are needed to determine the effect of statins on prostate cancer," she said.
In a second study, a research team led by Dr. Robert J. Hamilton, from Duke University Medical Center, found statins lower PSA levels. "In 1,200 men, we found an average 4.1 percent decline in PSA after starting their statin," Hamilton said. "The PSA dropped more if the patient was on a higher dose of a statin."
Moreover, men whose PSA was highest saw the greatest drop in PSA levels after starting statins, Hamilton said. "These men had an average of a 15 percent drop in their PSA," he noted.
Hamilton said studies need to be done to see if statins actually protect against prostate cancer. He added the concern that statins may not prevent cancer, but rather mask the malignancy through the decline in PSA levels, so some prostate cancers may go undiagnosed.
In a third study, a group headed by Dr. Teemu J. Murtola from the University of Tampere, Finland, collected data on 78,484 Finnish men between the ages of 55 and 67.
They found that there were fewer cases of prostate cancer among men who used statins. "There was a dose-dependent reduction in prostate cancer among users of statins, but not among users of other cholesterol drugs," Murtola said. "The overall risk of prostate cancer was around half of that of non-statin users."
In addition, Murtola's team found that PSA levels were also lower among study subjects without cancer who used statins.
"The association of statins with the reduced risk of prostate cancer should be made known to men taking statins," Murtola said.