Prostate Specific Antigen (PSA): Part III of a VII Part Article
(7/25/12)- The results of a 15-year study, that compared "watchful waiting" to radical prostate cancer surgery concluded that there was no benefit gained by the more aggressive treatment. The results of the research was published in a recent edition of The New England Journal of Medicine. The Department of Veterans Affairs, the National Cancer Institute and the Agency for Healthcare Research and Quality paid for the research.
Dr. Timoth J. Wilt, a professor of medicine at the Minneapolis Veterans Affairs Center for Chronic Disease Outcomes Research was the lead author of it.
The study concluded that there was no statistical difference in risk of death from prostate cancer or any cause among men who were randomly assigned to the surgery or the "watchful waiting" group.
About 100,000 to 120,000 radical prostatetectomy surgeries are performed in the U.S. each year. Approximately 242,000 men receive a diagnosis of prostate cancer, largely because of screening for high levels of P.S.A. in the blood, and about 28,000 will die from it each year.
The study called the Prostate Cancer Intervention Versus Observation Trial, or Pivot, had set out to enroll 2,000 men, but only 731 were enlisted.
By the end of the 15-year period of time, 354 men had died, but most of them from a cause other than prostate cancer. There was no statistical difference in overall mortality rates in the surgical group, which had 171 deaths, compared with the observation group, which had 183 deaths.
(5/27/12)- The U.S. Preventive Task Force recommended a "D" grade for prostate-specific-antigen, or PSA, testing which has been in use for over two decades to screen men for prostate cancer. The task force had recently recommended against the testing for men over 75 years-of-age. Please see our item dated 4/30/11 below
A "D" rating means "there is moderate or high certainty that the service has no net benefit, or that the harm outweighs the benefit. It is also a recommendation against the testing.
The task force said it conducted reviews of several large studies of PSA testing and that it concluded that they did not show the test improved any mortality rates. "Many men are harmed by prostate cancer screening" with a PSA test, said Michael LeFevre, the task force's co-chairman and a professor at the University of Missouri School of Medicine.
The task force is made up of 16 non-federal, primary care providers who review preventative health services and make recommendations, primarily for primary care doctors. The American Cancer Society estimates that 241,740 men will be diagnosed with prostate cancer and 28,710 will die from it.
(4/30/12)- In 2008, the United States Preventive Service Task Force recommended that men 75 and older no longer be given a routine PSA test. The Task Force felt that testing in men in that age grouping was unnecessary because the test is notoriously unreliable in older men, who often have elevated PSA scores as a result of aging or an enlarged prostate.
The cancer is slow growing in older men, so if the life expectancy is less than 10 years, there is no need to do the testing.
According to researchers from the University of Chicago, and the University of California, Los Angeles testing of men for PSA levels continues to go on unabated by the recommendation. The results of their study that collected data form the National Health Interview Survey were published online in The Journal of the American Medical Association.
The survey, on which the data is based, is done every five years and included 13 questions about PSA testing. Among the 5,332 men surveyed in 2005 and the 4,640 men questioned in 2010, the researchers found no difference in the rate of PSA testing among older men.
In both the 2005 and the 2010 survey, about 43 percent of the men were 75 or older. In fact, in the 2010 survey, PSA screening was more common in men 75 or older, than in men in their 40s and 50s.
(3/16/12)- It looks like the dilemma continues over whether to take a PSA test or not. On Wednesday March 14, 2012 the New England Journal of Medicine published a study that suggested PSA testing could save lives.
The study is called "European Randomized Study of Screening for Prostrate Cancer". It followed 162,000 men for 10 years. Results indicated that men who got regular PSA blood tests were 21% less likely to die of prostate cancer
Best estimates indicate that about 28,000 men will die of prostate cancer this year, with 241,000 men likely to survive and die of something else. Prostate cancer appears to be quite prevalent in men. Studies of men who have died of other causes found that 30% of men aged 50 and older and 70% of those 80 and older had prostate cancer and didn't know it.
Further studies have suggested that in order to prevent one death you would have to screen 1055 men with 37 men being diagnosed as having prostate cancer. This means that 36 men were eligible for treatment that may not have been necessary. The treatment itself may have adverse effects
To test or not to test for cancer now becomes an even more difficult dilemma for men with these latest studies. It boils down to a collaborative discussion with your treating physician, weighing all options and then, depending on your level of anxiety, making a decision. The kicker in all this brouhaha is the coverage by your health insurance company. How do they take the research results and use evidence-based medicine as the reason to pay or not pay?
(12/18/11)- Treatment can be delayed for low-risk prostate cancer patients until warranted by disease progression, according to an NIH panel.
Defining low-risk prostate cancer as prostate-specific antigen levels of less than 10 ng/mL and a Gleason score of 6 or less, the panel estimated that more than 100,000 men diagnosed with the cancer each year would not require immediate therapy, but only active monitoring.
(8/9/10)- Is aggressive treatment of prostate cancer warranted? In an analysis of the data that looked at the risk profiles and treatment patterns of 123,934 men whose prostate cancer cases were diagnosed between the years from 2004 through 2006 it was determined that the men probably would have benefited more from conservative rather than aggressive treatment of the disease.
Dr. Mark N.Stein, an assistant professor at the Cancer Institute of New Jersey, and one of the paper's authors stated: "We need to figure out if we can manage more men in a conservative manner." The results of the study were published in the July 26 issue of Archives of Internal Medicine.
Men with low levels of prostate-specific antigen (PSA) levels were treated as aggressively as those with high PSA readings in more than fifty percent of the cases. The intensive treatment included surgery or radiation therapy, even though the cancer was unlikely to spread or to be fatal.
(3/30/09)- The interim data from the results of two large, long term studies of the results of prostate specific antigen (PSA) that were published in a recent edition of the New England Journal of Medicine indicated that the test saves few if any lives.
The bottom line of both studies was that PSA screening does find more prostate cancer, but finding those cancers does not do much to reduce the death rate of the patient.
The European study data looked at 7 different European country studies that together enrolled 162,243 men, age 55 to 69. The American study, by the National Cancer Institute, involved nearly 77,000 men at 10 medical centers in the U.S.
In both studies, the participants were randomly assigned to be screened or not. No restriction was placed however on any individual who was not enrolled to be screened from going out on his own and getting himself screened. In each study, the two groups were followed for more that a decade.
The American study showed no statistical difference in prostate cancer death rates between the group of men who were screened as opposed to those who were not screened. In this study, so far only 170 men out of the 77,000 studied have died of prostate cancer. Dr. Barnett S. Kramer an associate director for disease prevention at the National Institutes of Health and Dr. Gerald L. Andriole Jr, a surgeon at Washington University were co-authors of the article appearing in the Journal.
In each group there were approximately 200 deaths per million men each year. In the English study, the men in the screening group has a death rate from prostate cancer of 350 deaths per million per year from prostate cancer versus 410 deaths per million per year in the non-screened group.
The European study found that for every man who was helped by a PSA screening, at least 48 received unnecessary treatment that increased risk for impotency and incontinence. The European research found that PSA screening did find a 20% reduction in cancer deaths among those who were screened as opposed to those who were not screened, but again the question arises as to whether or not it is worth the difference.
Both of these major studies are continuing and therefore it remains to be seen what evolves since prostate cancer is such a slow growing tumor. PSA screening tests were first introduced in this country in 1987.
In October 2008 a study of 35,000 men concluded that there were no benefits towards lowering the risk of prostate cancer shown for individuals who took high doses of vitamin E and selenium. Dr. Eric Klein, national study coordinator for the study, and who is also chairman of the Cleveland Clinic's Glickman Urological and Kidney Institute stated: "The public's belief in the benefits of vitamins and nutrient is not supported by the available scientific data."
The Select trial followed 35,333 men from 427 locations in the United Stated, Canada and Puerto Rico for more than 5 years. It found no benefit in the group taking 400 I.U.'s a day of vitamin E, Selenium or from taking the two of them in combination.
(1/5/09)- The U.S. Food and Drug Administration (FDA) recently approved the injectable drug degarelix, the first new drug in several years for prostate cancer treatment. Degarelix is intended to treat patients with advanced prostate cancer.
It belongs to a class of agents called gonadotropin releasing hormone (GnRH) receptor inhibitors. These agents slow the growth and progression of prostate cancer by suppressing testosterone, which plays an important role in the continued growth of prostate cancer.
(8/12/08)- The U.S. Preventive Services Task Force was created by Congress and first convened in 1984 to analyze current medical research and to make recommendations about preventive care for healthy people. Its guidelines are highly respected by most medical professionals.
In a recent pronouncement, the task force recommended that doctors stop administering PSA testing for men ages 75 and above because the search for the disease in this age group was causing more harm than good.
The task force still has not taken a stand on the value of PSA screening for younger men, whereas both The American Cancer Society and the American Urological Association both say annual such screening should be offered to average-risk men 50 and older, if they have a greater than 10-year life expectancy.
Last year more than 218,000 men were diagnosed with prostate cancer.
A major clinical trial is presently underway in Europe to try and determine whether there is any value in terms of longer life expectancy, to screening older men for prostate cancer. Those results may be published as early as next year
(1/25/08)- ProActive Genetics will have available for sale in a few months a DNA testing device that looks at five areas that the company feels can help a man predict whether or not he will get prostate cancer.
ProActive is a company that was formed by researchers at the Wake Forest University School of Medicine. The testing kit is expected to cost about $300.
The researchers found that about 90% of the men in their study had one or more of the gene variants and more that half had two or more. The cancer risk increased substantially when men had four or five of the variants.
Men with four or five of the variants make up only 2% of the study population but had a 4.5% increased risk of having prostate cancer compared with men who had none of the variants. If the men also had a family history of prostate cancer, their risk was nearly 10 times higher than that of men with none of the risk factors.
The question arises however as to whether the cost involved in finding the DNA risk through the testing kit is worth the expense, and if it unnecessarily leads to costly additional testing and anxiety.
(11/27/07)- Because obese men have more blood in their bodies their PSA test may show them to be cancer free when in fact this is not necessarily so. According to the results of a research report that appeared in a recent edition of The Journal of the American Medical Association, Dr. Stephen Freedland, the lead researcher for the study stated: "It's not that PSA is a bad test, in obese men" "Rather, we just need to learn how to use it better."
Androgen deprivation therapy, which is commonly used to treat men with prostate cancer, causes weight gain, thus predisposing men to diabetes and the metabolic syndrome. (Family Practice News, April 15, 2007, p. 34)
(5/22/07)- The following is an email that we received from Laurie Cooper, one of our viewers, whom we wish to thank for her excellent suggestion:
I browsed through your website and found it useful. I would like to make a contribution by suggesting some websites for addition to your web links collection.
Your section, - Prostate Specific Antigen (PSA): Part II - http://www.therubins.com/aging/prostate2.htm
My suggestion, - http://www.healthopedia.com/prostate-cancer/
You could add corresponding relevant links from- http://www.healthopedia.com/
I am positive that these resources might prove useful to your website visitors.
Thanks for your valuable time and have a nice day.
(4/1/07) As we previously wrote (11/25/06), PSA screening in the elderly is fraught with risk. A recent study in JAMA 2006; 296(19):2336-2342, attempted to characterize the extent of PSA screening among 597,642 elderly men (median age 77 years), including those with limited life expectancies.
The descriptive study, using VA data and Medicare claims, looked at elderly veterans PSA screening rates stratified into 4 subgroups (70 to 74 years, 75 to 79 years, 80 to 84 years and 85 years and older), and a validated measure of health status that is strongly predictive of life expectancy. Health status was measured with the Charlson Comorbidity Index, which categorized the men as best health if they had a score of 0, average health score of 1 through 3, and worse health if they had a Charlson score of 4 or more.
Results indicated that the percentage of men who underwent a PSA test decreased with advancing age, but did not decrease as much as estimated 10-year survival rate. Simply put, worsening health was associated with a small decrease in PSA screening.
As the researchers point out: 36% of veterans aged 85 years or older were screened, whereas less than 10% of men in this age group are expected to survive 10 years. They conclude that the high rates of screening of the elderly with limited-life expectancies in the VA system is considerably inappropriate. The investigators feel that the screening exposes immediate and substantial harm.
False positive results requiring needle biopsies or cycles of repeat testing and anxiety. Interestingly, they cite two studies suggesting that 2 out of every 3 cancers detected by screening men between ages 70 to 75 years would never have produced symptoms during their lifetime. (J Natl Cancer inst. 2003 95:868-878 and J Urol 1990; 143:742-746)
The summarized conclusion from the study is prostate specific antigen screening rates among elderly veterans with limited life expectancies should be much lower than current practice given the known screening harms of screening. More attention to prognosis is needed when making screening PSA recommendations to elderly men.
(11/25/06)- We think that it is important to point out that the U.S. Preventive Services Task Force, the American College of Physicians and several other groups do not support routine PSA screening. The worry is that widespread screening with PSA is resulting in too many painful biopsies, or that the cancer that is found is so slow growing that it is best left untreated but followed closely.
The National Cancer Institute says that a PSA score of 2.6 to 10 ng/nil is slightly to moderately elevated. Only 25% to 30% of men who have a biopsy due to elevated PSA levels actually have prostate cancer.
As far as "velocity" of change goes most medical professionals feel that an annual change ranging from 0.35 to 0.7 may now trigger a biopsy. "Velocity" refers to the change in score from one PSA reading to another.
"One in six American men receives a diagnosis of prostate cancer during his lifetime, usually after 60 years of age. With approximately 234,000 new cases expected in 2006, prostate cancer is the most common noncutaneous malignant disease and the third leading cause of cancer-related death in men." (Pisansky, T. N Engl J Med 2006: 355 (15): 1583-1591)
(11/12/06)- Will it be worth the expense of having a man take Prostate Specific Antigen (PSA) tests starting at the age of 40 instead of the presently recommended age of 50, or is the cost not worth the effort? Scientists at the Johns Hopkins University School of Medicine in Baltimore have concluded that it is worth starting the test at the earlier age, since it can form the basis in determining how deadly the cancer may be, if it does develop.
The result of the study was recently published in the Journal of the National Cancer Institute. H. Balentine Carter, a professor at Johns Hopkins, led the study The Hopkins study shows that a single PSA score is not that meaningful, and that what is the real key is the change in the score over time. Thus, if there is a longer time frame in which to make the comparison, the more accurate of a prediction can be made as to the severity of the disease.
Presently, it is estimated that there are about 1.6 million PSA tests administered each year, but only 234,000 men are diagnosed with prostate cancer. The Hopkins study looked at PSA scores from 980 men in the Baltimore Longitudinal Study of Aging (BLSA), the country's longest-running scientific study of human aging.
The researchers compared the PSA tests of men who died of cancer as opposed to those who remained free of the disease. The data showed that a man whose PSA score increased by 0.35 ng/nl or more each year would see a fivefold increase in the risk of dying from prostate cancer in the next two to three decades.
The researchers concluded that if they could compare the data over the longer period of time, that the disease could be caught and treated sooner, and thus save the lives of hundreds of thousands of men. By using "PSA velocity" doctors could identify men with slow growing cancers that don't need any treatment.
(1/18/06)- A small study that involved only 1,002, that was done under the co-leadership of John Concato, a clinical epidemiologist at the VA Connecticut Healthcare System concluded that two widely used tests for prostate cancer failed to save lives.
The research involved two screening tests that are used on millions of men throughout the world, namely the PSA test, and a digital rectal exam ( the rubber-glove test in which a doctor feels for abnormalities in the prostate through the rectal wall).
The researchers compared two groups of men treated at 10 Veterans Affairs medical centers. The findings support an earlier review by the U.S. Preventive Services Task Force. The agency said in 2002 that it found that there was "insufficient evidence" for a recommendation that all men be screened.
(9/30/05)- A very small study, the results of which were published in the New England Journal of Medicine concluded that there is a more accurate method of detecting prostate cancer. The study involved only 257 blood samples of men who had enzyme PSA readings of between 2.5 and 10 billionths of a gram per milliliter.
Researchers at the University of Michigan and Harvard have developed a different kind of test that relies on the body's immune system for the vital clue as to whether or not cancer is present in the individuals system. The test looks for particular antibodies in the blood.
Only about 40% of the men who have elevated PSA levels of over 4 are found to have cancer after a biopsy is performed. The American Cancer Society projects that about 30,000 men will die of prostate cancer, which is the second leading cause of cancer deaths among American men. Only lung cancer exceeds the death rate of prostate cancer among men in this country.
The new test looks for particular antibodies, or disease fighting proteins, that the immune system issues in response to cancerous tissues. In the study the test was accurate in predicting cancer 94% of the time.
(11/28/04)- The U.S. Preventive Services Task Force (USPSTF) concludes that the evidence is insufficient to recommend for or against routine screening for prostate cancer using prostate specific antigen (PSA) testing or digital rectal examination (DRE).
Rationale: The USPSTF found good evidence that PSA screening can detect early-stage prostate cancer but mixed and inconclusive evidence that early detection improves health outcomes. Screening is associated with important harms, including frequent false-positive results and unnecessary anxiety, biopsies, and potential complications of treatment of some cancers that may never have affected a patient's health. The USPSTF concludes that evidence is insufficient to determine whether the benefits outweigh the harms for a screened population. (http://www.ahrq.gov/clinic/3rduspstf/prostatescr/prostaterr.htm accessed on November 24, 2004.
(4/3/04)-Researchers from Harvard and Washington University in St. Louis studied PSA levels in nearly 7,000 men, and concluded that it is an error to wait or the PSA score to reach 4 before reacting to this reading. According to the researchers physicians who wait until a man's PSA reaches 4 before recommending a biopsy may be missing 82% of cancers in men under 60 and 65% of cancer in men over 60.
Prostate cancer is the second leading cause of death among U.S. men. Each year nearly 200,000 men are diagnosed with prostate cancer, and 30,000 men die annually of the disease. As a result of the study, the researchers concluded that doctors should consider ordering a biopsy when the score is 2.5 or higher depending on the particulars of the individual involved in the test. This is their conclusion even though only a 25% chance of there being a cancer when the reading is higher than 4. That means that 3 out of 4 men do not even need the test.
Other medical professionals believe that only if there is a yearly increase of 0.7% or more should a biopsy be ordered. PSA levels and cancer risk also chage depending on a man's age, race and the size of his prostate.
Researchers at the Cancer Institute of New Jersey in New Brunswick, N.J. have concluded that "There is no evidence that (PSA) screening men of this age (75 years or older) would be beneficial to them, so this may not be the best use of health-care resources." According to Siu-Long Yao, a genital-urinary oncologist, who lead the research group: "Diagnosing the prostate cancer may lead to unnecessary complications in the elderly patients who are more likely to die of something else, such as cardiovascular disease."
The PSA test does not directly detect cancer. The test determines whether or not a patient has too much prostate tissue. That excess tissue can be caused by inflammation, by enlargement common to older men or by cancer. Further testing has to be performed before it can be determined whether or not the patient has prostate cancer. The test however can be quite important when the previous history of the patient puts him at serious risk to develop prostate cancer. In a survey of 7,889 men, researchers found that 32.5% of the men over 75 received PSA blood tests.
According to a study done under the leadership of Dr. Rinaa Punglia, PSA testing misses 82% of tumors in men over 60 because a reading over 2.6 should be considered the critical level for follow-up biopsies. At present most experts, and the American Cancer Society, consider a reading over 4 as the critical level above which a biopsy should be performed. The American Cancer Society's research evaluation indicates that a reading less than 10 meant only a 25% chance of having prostate cancer. If the level exceeds 10, the cancer risk is more than 67%.
Other experts sharply disagreed with Dr. Punglia's conclusion. The biopsy procedure is both painful and expensive. At the same time the anxiety level that it would cause is totally unnecessary. The results of the study were published in The New England Journal of Medicine.
In an interesting development, researchers at Harvard University think that they may be onto a new technique to determine whether or not an individual has prostate cancer. The researchers have discovered a tiny protein called Pca-24, which was found in the tissues of 16 of the 17 men, examined who had prostate cancer. None of the 12 men who had enlarged prostates had this protein. Obviously this is an extremely small group on which to base any definite conclusions, but it is an area that will be followed up on. The research technique involved is called proteomics.
Sixteen percent of men develop prostate cancer in their lifetimes, but only 3 % die from it. Scientists are hoping in their follow-up research on the protein, that prostate-cancer cells create it. There are two small closely held companies that hope to have commercially available prostate screens available within one year that can test for the protein. The machine that is used in proteomics research is called a "mass spectrometer" and costs about $200,000. The two companies that are working on the commercial availability for the test are Correlogic Systems Inc. of Bethesda, Md., and Matritech Inc., of Newton, Mass.
There will be an estimated 220,900 cases of prostate cancer diagnosed in men in this country this year. According to the American Cancer Society about 28,900 men will die as a result of the disease in 2003. It is the second leading cause of cancer deaths among men in this country exceeded only by lung cancer fatalities.
In a recent study done on 972 men at the Memorial Sloan-Kettering Cancer Center in Manhattan, the researchers concluded that doctors should repeat the PSA test after waiting 4 to 6 weeks on men who had had scores on their PSA levels. Dr. James A. Eastham led the research group. The study concluded that in over half the men that were subsequently tested, the level fell back to normal in second test. "No one should be referred for a biopsy based on one single P.S.A. test that's slightly elevated," said Dr. Eastham. A biopsy can cost up to $1,500 to have performed on an individual.
In general most urologists agree that since prostate cancer grows so slowly a wait of 4-6 weeks in performing the 2nd test no undue risk is taken by waiting before taking the 2nd test. False positives occur frequently in P.S.A. tests since there are many other factors besides cancer that can cause the elevation in the P.S.A. level. The aging process alone causes an enlargement of the prostate that can cause the higher readings. A score of 4 or more is considered a high reading that should be followed up on.
Citing inadequate data, the U.S. Preventive Services Task Force has no recommendation, either for or against P.S.A. testing. When the blood level of PSA. rises above 4 nanograms per milliliter, doctors usually urge either a free radical PSA test or a biopsy. Cancer will be found in about one half of those patients, but it may never become symptomatic or life threatening. Although the cost of the PSA. test is minimal the cost of a biopsy may run as high as $1, 500. If a cancer is found, there is no certainty as to how deadly it is, or even if it will ever be deadly. One must also take into consideration the anxiety level that arises as a result of the test results of the PSA. test when in fact it was not warranted.
In autopsies of men over 50, as many as half of them have been found to have cancer cells in the prostate that have neither spread nor caused symptoms to the patient. In men over 80, about 70% showed some signs of cancer. Prostate cancer killed about 30,000 men last year. A major study is now under way at 222 sites to try and determine the true value of both PSA. testing and digital rectal exams for three consecutive years. The study is called the Prostate Cancer Prevention Trial, and men from the ages of 55 to 74 will be followed for a 10-year period of time. Some experts in the field urge that sequential testing be used to help determine the risk level for a particular patient. Thus if the P.S.A. level rises by 25% or more follow-up tests should be performed.
At a news conference on February 11, 2003, Senator John F. Kerry, 59 years old, disclosed that he had prostate cancer and would have his prostate removed. Mr. Kerry is one of the Democratic presidential candidates seeking nomination for the presidency in 2004. His cancer was first noticed when he had a routine screening blood test, the PSA, which detects a protein that leaks from the prostate. This screening seeks to identify a group of men with early stage prostate cancer in whom prompt radical treatment will alter outcome.
As we have written previously, there is some controversy about PSA screening. Evidently, many prostate cancers do not become clinically significant and do not need to be aggressively treated. The main forms of radical treatment are radical prostatectomy or radiotherapy (external beam or brachytherapy). Both forms carry a significant side-effect profile, particularly with regard to sexual function and incontinence rates, quite apart from the pain and hospitalization required for the procedure. It still remains unclear which tumors merit such drastic treatment. In Mr. Kerrys case, his doctor, Patrick C. Welsh of Johns Hopkins Hospital, who has had experience with 2000 patients who were followed for a decade after surgery, indicated that the chances of Mr. Kerry having incontinence as a side effect were 3 to 4 percent. He further indicated that Mr. Kerry had a 90% chance of recovering his sexual function and that there is a 95% chance that Mr. Kerrys cancer will be undetectable when the test is done 10 years after the operation.
Prostate tumors are graded on a scale called the Gleason score. Mr. Kerrys score was 6, with the most aggressive tumors at the high end of the scale. Mr. Kerry has another risk factor. His father died of prostate cancer at the age of 85, 10 years after his prostate was removed. For men with prostate cancer, 13% have an affected first-degree relative, compared with 5% for a controlled population. The relative risk conferred by having an affected first-degree relative is between 2.2 and 2.7 times the population mean, The research literature suggests that men over 75 are not considered candidates for either prostatic radiotherapy or radical prostatectomy, because their actuarial life expectancy is less than 10 years. (3). In fact, some researchers suggest an upper limit of 70 for testing (4).
As far as testing is concerned, only one study has shown a decrease in the prostate cancer death rate from screening. This was the Quebec Screening Trial (8) of 46,198 men, which showed a significant fall in prostate-specific deaths, from 49/100000 to 15/100000. It would appear that much of the early benefit of screening comes from prompt initiation of hormonal treatment of men with metastatic prostate cancer (14).
Crawford et al (2) suggest that the chances of detecting prostate cancers are higher if both PSA and digital rectal examination are used. In their study, 116,073 individuals were screened with a PSA test and digital rectal examination. They found the predictive value of PSA alone, with a cut off level of 4.0 ng/ml, was 28%, for a digital rectal examination alone the predictive value was 18%, but when both were abnormal, 56% of the men had a cancer. They further determined that when they used an age-specific reference PSA level, the positive predictive value rises to 64% if both are abnormal.
It is well known that PSA values rise with age. It is why some physicians suggest that it is more advisable to use age-referenced values of PSA. Gustafsson (4), in his study of 1782 men, came up with the following age-related mean values for the PSA test: 55-59 years5.2; 60-64 years5.8; 65-70 years6,7. Another research group, Oesterling et al (12), used the following criteria: 45-49 years2.5; 50-59 years3.5; 60-69 years4.5; 70-79 years6.5. The higher reference ranges in older men did not dramatically reduce the chances of discovering a potentially curable cancer.
Keep in mind that PSA test results may show intraindividual variation (7). The same person may have a different PSA result on different days. Difference in diet is thought to explain some of the heterogeneity in clinical prostate cancer incidence observed worldwide. Epidemiological data have also revealed a significant inverse relationship between ultraviolet radiation and prostate cancer mortality, suggesting that increased ultraviolet radiation and subsequent vitamin D synthesis may be associated with a reduced risk of prostate morbidity (13.)
Berndt et al (1) studied this hypothesis and found "No significant association or trends between calcium, phosphorous, vitamin D, fructose and animal protein and the risk of prostate cancer Dairy products were not significantly associated with prostate cancer No significant trend was found between higher milk intake and risk of prostate cancer. No difference in prostate cancer risk was observed among different types of milk (whole, low fat, and skim)". These researchers concluded that their study suggest calcium intake within moderate limits is not associated with a notably increased risk of prostate cancer. This study appeared to contradict the study by Hayes and his group that showed a high intake of dairy products to be associated with an increased risk of prostate cancer. They may not be contradictory because of the words they use in their conclusion: "moderate" and "high" intake. Too much is potentially bad, with moderate not harmful.
Research has further indicated that when the cut-off score of 4.0 ng/ml or higher is used,and clinical diagnosis of prostatitis, benign hypertrophy (BNH) are excluded, then 17-27% of the cases biopsied will be positive for carcinoma (10). Hugosson et al (6) showed that when frozen blood samples were tested for PSA in a group of 658 men, aged 67 years, sixteen years later, the risk of developing prostate cancer within 15 years of a PSA score of 3-10 was 22 percent, rising to 45%, if the PSA was >10ng/ml.
What is alarming in all this research is that prostate cancer can subsequently be detected in patients whose PSA is below 4.0ng/ml. Ito et al (7) has shown that the risk, as determined from a cohort of 8595 men over 50, who tested between 2.0 and 4.0ng/ml, was 1.2% after 3 years. This group recommended that screening in this PSA range should take place annually, and for lower values every three years. The Gustafsson study (4) estimated that chances of a 67 year old man developing cancer with an initial PSA of 3 ng/ml or less, was 3.6% during the next 15 years.
This review of the research literature is suggestive of the caution one should take in evaluating the results of PSA testing (11). Could it be that the PSA testing is including many individuals who will not develop prostate cancer in their lifetime and are subjecting themselves to a painful experience with aggressive treatment? It suggests careful collaboration with the treating physician about steps to be taken. There is a strong need for risk-cost benefit analysis.
We would recommend the following web sites for further information about PSA:
http://www.prostate.com/ This site advises "Men over the age of 50, and those men over the age of 40 who are in high risk groups such as African-American men and/or men with a family history of prostate cancer, should have a PSA blood test and digital rectal examination once every year.
http://www.cancereducation.com/ This site is aimed at both physicians and patients.
http://www.psa-rising.com/ A pro-testing patient-centered website..
Berndt SJ, Carter HB, Landis P, Tucker KZ. et al. Calcium intake and prostate cancer risk in long-term aging study: The Baltimore Longitudinal Study of Aging. Urology 2002; 60: 1118-1123.
Crawford ED, Leewansangtong S, Goktas S. et al. Efficiency of prostate-specific antigen and digital rectal examination in screening, using 4.0 ng/ml and age-specific reference range as a cut-off for abnormal values. Prostate 1999; 38(4): 296-302.
Dearnaley DP, Kirby RS, Kirk D, et al. Diagnosis and management of early prostate cancer, report of a British Association of Urological Surgeons working party. Br J Urol Int1999; 83(1): 18-33. Gustafsson D, Mansour E, NormingU. et al. Prostate-specific antigen (PSA), PSA density and age-adjusted PSA reference values in screening for prostate testing: a study of randomly selected population of 2400 men. Scand J Urol Nephrol 1998; 32(6): 373-377.
Hayes RB, Ziegler RG, Gridley G et al. Dietary factors and risk for prostate cancer among blacks and whites in the US. Cancer Epidemiol Biomarkers 1999; 80: 1107-1113.
Hugosson J, Aus G, Becker C. et al Would prostate cancer detected by screening with prostate-specific antigen develop into clinical cancer if left undiagnosed? A comparison of two population-based studies in Sweden. Br J Urol Int 2000; 85(9): 1078-1084.
Ito K, Kubota Y, Yamamoto T. et al. Long term follow-up of mass screening for prostate carcinoma in men with initial prostate specific antigen levels of 4ng/ml or less. Cancer 2001: 91(4): 744-751.
Labrie F, Candas B, Dupont A et al. Screening decreases prostate cancer death: first analysis of the 1988 Quebec prospective randomized controlled trial. Prostate 1999; 38(2): 83-91. Lamm DL. Long-term results of intravesical therapy for superficial bladder cancer. Uro Clin North Am 1992; 19:373-580. LuboldtHJ, Bex A, SwobodaA et al. The Early Detection Project Group of the German UrologicalAssociation. Early detection of prostate cancer in Germany: a study using digital rectal examination and 4.0ng/ml prostate-specific antigen as cut-off. Eur Urol 2001; 39(2): 131-137.
Neal DE, Leung HY, Powell PH et al. Unanswered questions in screening for prostate cancer. EurJ Cancer 2000; 26: 1316-1321.
Oesterling JE, Jacobson SJ, Sooner WH. The use of age specific reference ranges for serum prostate specific antigen in men 60 years old or older. J Urol 1995; 153: 1160-1163.
Schwartz GG, Hulka BS. Is vitamin D deficiency a risk factor for prostate cancer (hypothesis)? Anticancer Res 1990; 10: 1307-1311.
Whitmore WF. Localized prostate cancer: management detection issues. Lancet 1994; 343: 1263-1267.
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Basic Information on Prostate
Predicting Survival After Prostate Surgery -Part II
Prostate Specific Antigen- Part IIIa
Prostate Cancer-Colon Cancer- An Overview - Part V
New Drugs in the Battle Against Prostate Cancer -Part VI
Also please see: Justice Ruth Bader Ginsburg and Colon Cancer
FOR AN INFORMATIVE AND PERSONAL ARTICLE ON PRACTICAL SUGGESTIONS WHEN SELECTING A NURSING HOME SEE OUR ARTICLE "Selecting a Nursing Home"
by Allan Rubin and Harold Rubin MS, ABD, CRC, Guest Lecturer
updated July 25, 2012
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