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Conflicting data cause confusion on prostate cancer screening

PSA levels aren't a perfect marker for cancer, experts say. But research shows that the incidence of metastatic disease has decreased since implementing PSA tests.

By Christine S. Moyer — Posted Aug. 13, 2012

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When he was a resident during the 1980s in Kentucky, a majority of the men Leonard Gomella, MD, treated for prostate cancer had an advanced stage that already had spread to other parts of their bodies. The men usually died of cancer within a year or two after being diagnosed.

Since that time, however, the incidence of metastatic prostate cancer in the U.S. has decreased, and fewer men are dying of the disease, data show. Dr. Gomella is among those who attribute the progress, in part, to earlier identification of prostate cancer through use of the prostate-specific antigen test.

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Dr. Gomella

“Our only option was to surgically castrate these men or treat them with estrogens, and they died a year or two later. I don't want to go back to those days,” said Dr. Gomella, now chair of the Dept. of Urology at the Kimmel Cancer Center at Thomas Jefferson University in Philadelphia.

Yet controversy continues to surround the PSA test as studies regularly present conflicting data on the efficacy and impact of this cancer screening.

For example, a July 30 Cancer study shows that doing away with PSA testing for prostate cancer probably would cause three times as many men to develop advanced disease that spreads to other parts of the body before being diagnosed. On the other hand, an April 17 Annals of Internal Medicine article indicates that PSA-based screening doesn't reduce the risk of prostate cancer mortality or all-cause mortality.

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Dr. Flanigan

Such conflicting research has left some primary care physicians torn about which patients, if any, they should screen for prostate cancer and what to do when men have elevated PSA levels.

Complicating matters is the U.S. Preventive Services Task Force's May recommendation that urged physicians to stop using the PSA test to screen men for the disease. The guidance does not apply to men who have been diagnosed with prostate cancer or are being treated for the disease.

“I have great sympathy for the primary care doctors with their feet on the ground, because this is a big problem, and we're not giving them a lot of guidance,” Dr. Gomella said. “If a physician does not do PSA screening and the patient gets diagnosed with prostate cancer, the legal system then cuts in, and you really have no protection. That's the sad thing.”

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Dr. Roberts

At the root of the controversy: PSA levels are not a perfect marker for prostate cancer, doctors say. A man's PSA can rise for various reasons, including the presence of benign prostatic growth and infection, said Robert Flanigan, MD, chair of the Dept. of Urology at Loyola University Medical Center in Chicago.

Though the PSA test indicates when levels rise, it can't identify the cause of that elevation, nor can it always differentiate between aggressive cancer and that which is slow-growing, doctors say. The lack of specificity can lead to biopsies and treatment of prostate cancer that never would have harmed the patient, said Pittsburgh internist Mark S. Roberts, MD.

Staying up to date with information

During a 10-year period, up to 20% of men will have an abnormal PSA test result that triggers a biopsy, according to a European study cited by the task force in its May recommendation. Research shows that a biopsy causes a negative side effect in about 68 per 10,000 biopsies, the task force said. Such side effects include fever, bleeding and infection from biopsies, and urinary incontinence and erectile dysfunction due to radiotherapy and surgery.

Some doctors and patients “can't believe that if you find cancer, doing nothing is sometimes the best choice,” said Dr. Roberts, a professor of medicine, health policy and management at the University of Pittsburgh.

“There are clearly versions of prostate cancer that really hurt you and cause morbidity and death and pain,” he said. “Unfortunately, the testing we have now doesn't tell us which prostate cancers are the ones we have to do something about and the ones we don't.”

Dr. Roberts encourages physicians to stay current on the subject by reading reports on the latest findings, which often are published by physician groups and medical organizations to keep doctors informed.

Health professionals agree that it's beneficial for physicians to be aware of prostate cancer screening guidelines, such as those issued by the task force. But Dr. Gomella urges physicians to remember that such guidance is not a standard of care but a recommendation.

“I say to primary care physicians, 'Follow what you believe is the best arrangement for your patients,' ” he said. “But at the end of the day, [a physician's actions should be guided by] informed decision-making.”

Prostate cancer is the second-most commonly diagnosed cancer among U.S. men and remains the second-leading cause of cancer death in men after lung cancer, according to the American Cancer Society. The organization estimates that there will be 241,740 new cases of prostate cancer diagnosed in 2012, and 28,170 men will die of the disease. Seventy percent of those who die will be older than 75, the National Cancer Institute said.

European researchers found that PSA screening every two to seven years was associated with a 20% relative reduction in risk of prostate cancer death in men age 55 to 69, said a 2009 study in The New England Journal of Medicine. A U.S. study published in 2011 in the Journal of Clinical Oncology found that screening was associated with reduced prostate cancer mortality for men with no or minimal comorbidities, but not for men with at least one significant comorbidity. A significant comorbidity was defined as one that could increase the risk of dying of cardiovascular disease or cancer.

“The conflicting data have made [prostate cancer screening] more confusing,” Dr. Roberts said.

When an asymptomatic patient asks him for a PSA test, he inquires about why a patient wants the screen. Dr. Roberts then discusses with the patient the controversy surrounding PSA screening and the potential harms in identifying cancer that might be slow-growing.

“It's never wrong to tell your patient, 'We don't really know what the right thing to do is,' ” he said.

When a patient still wants the screen, Dr. Roberts orders it but tells him, “We have to be careful with how we interpret the results.”

If the PSA is elevated, he recommends that physicians inform patients about the risks of biopsy. If cancer is detected, the physician should discuss the potential harms of treatment. Before deciding on a care plan, he encourages doctors to consider the individual's preferences and values.

Urologist Edward M. Messing, MD, urges physicians to remember that ordering a PSA test doesn't mean that they have to follow up with a subsequent procedure. They could choose to wait and see if there are changes in the patient's health and PSA levels.

“To just eliminate the test is really stealing from patients the option to be involved in a decision that could be very serious for them,” said Dr. Messing, chair of the Dept. of Urology at the University of Rochester Medical Center in New York. He also is senior author of the July 30 Cancer study on the impact of abandoning PSA testing for prostate cancer.

Screening recommendations

Medical organizations have varying positions on prostate cancer screening. The American Medical Association recommends that physicians educate men who are interested in prostate cancer treatment about their risk of developing the disease and the potential benefits and harms of screening.

The AMA House of Delegates in June adopted policy expressing concern that the task force recommendation against the PSA test for prostate cancer would limit access to preventive care. The policy states that the AMA will encourage the task force to implement procedures to allow for greater input from specialists when drafting prevention recommendations.

“Most of us believe that the PSA is not a perfect marker,” said Dr. Flanigan, of Loyola. “But it's foolhardy to stop using it until we have a substitute test or a different agreed-upon way to use the test.”

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ADDITIONAL INFORMATION

What recent research says about prostate cancer

Studies often present conflicting data on the efficacy and impact of using the prostate-specific antigen test for prostate cancer screening. In July, at least three reports addressed the issue.

  • July 30, Cancer: Abandoning PSA screening for prostate cancer likely would lead to about three times as many men presenting with metastatic disease when they are diagnosed with the illness (an estimated 25,000 people). The findings were from a study of Surveillance, Epidemiology and End Results Program data on more than 5 million U.S. men.
  • July 25, Journal of the National Cancer Institute: Men diagnosed with prostate cancer are less likely to die of the disease than of another cause, according to data gathered on the cause of death of more than 700,000 U.S. and Swedish men who had prostate cancer.
  • July 19, The New England Journal of Medicine: Among men with localized prostate cancer detected during the early era of PSA testing, radical prostatectomy did not significantly reduce all-cause mortality or prostate cancer mortality when compared with watching and waiting. The study was based on data of 731 men with localized prostate cancer who were randomly assigned between 1994 and 2002 to surgery or observation. The men were followed through January 2010.

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External links

“Prostate-Specific Antigen Screening for Prostate Cancer and the Risk of Overt Metastatic Disease at Presentation,” Cancer, published online July 30 (link)

“Review: PSA-based screening does not reduce prostate cancer mortality or all-cause mortality,” Annals of Internal Medicine, April 17 (link)

Screening for Prostate Cancer, U.S. Preventive Services Task Force current recommendation, May (link)

“Screening for prostate cancer: a review of the evidence for the U.S. Preventive Services Task Force,” Annals of Internal Medicine, published online Oct. 7 (link)

Prostate cancer information, American Cancer Society (link)

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