PSA test better predicts cancer in men taking prostate-shrinking drug

The PSA screening test for prostate cancer is not perfect. It can indicate cancer when none is present and miss life-threatening tumors. But a new study suggests the test is more reliable in men taking dutasteride , a drug widely prescribed to shrink an enlarged prostate gland.

21 dec 2010--Dutasteride lowers PSA levels by about half within six months. But the researchers found that even a slight rise in PSA levels among men taking the drug was a stronger indicator of prostate cancer, particularly aggressive tumors that require early diagnosis and treatment, than rising PSA levels in men who took a placebo.

"Dutasteride stabilizes the amount of PSA that comes from enlarged prostates and low-grade cancers," says lead author Gerald Andriole, MD, the Robert Killian Royce, MD, Distinguished Professor and chief of urologic surgery at Washington University School of Medicine in St. Louis. "This enhances a rising PSA's ability to detect high-grade cancers that require early diagnosis and treatment, while reducing the discovery of tumors that are unlikely to cause harm if left untreated."

The study is now available online and will be published in January in the Journal of Urology.

The PSA test measures the amount of prostate-specific antigen in the blood. The larger a man's prostate, the more PSA he produces. Elevated levels can point to cancer. But PSA often rises naturally as men age, mainly due to benign prostatic hyperplasia (BPH), a progressive enlargement of the prostate. This leads to many false positive PSA tests for cancer. Indeed, biopsies only find cancer in about one in four men with an elevated PSA.

In the new study, the researchers looked more closely at data from a four-year trial that evaluated whether dutasteride could reduce the risk of detecting prostate cancer in men with an increased risk of the disease. The study involved 8,231 men ages 50-75 who were randomly assigned to receive a placebo or a daily 0.5 mg dose of dutasteride. The men had elevated PSA levels (2.5 ng/ml-10 ng/ml) but no evidence of cancer on biopsies performed within six months of enrolling in the trial.

Results published earlier this year in the New England Journal of Medicine showed that dutasteride reduced the risk of a prostate cancer diagnosis by 23 percent. Dutasteride appears to keep tumors small or shrink them to the point that they are less likely to be detected by a biopsy, says Andriole, who led the steering committee that oversaw the earlier trial.

In the current analysis, the researchers looked at the performance of PSA as a marker for prostate cancer, particularly for aggressive cancer. Among men taking dutasteride, the investigators found that any subsequent rise in PSA levels over the course of the study was more likely to be linked to aggressive, high-grade tumors (Gleason score 7-10), compared to rising PSA levels in men on a placebo.

The Gleason scoring system measures tumor aggressiveness based on biopsy results and can range from 2-10, with 10 being the most aggressive.

"If a man is taking dutastride and his PSA level starts to rise, he has a higher chance of having an aggressive cancer," Andriole says. "This makes PSA a more effective screening tool for prostate cancer but even more importantly for aggressive cancer."

Over four years, PSA levels increased in 72 percent of men taking a placebo and only 29 percent of men taking dutasteride, the data show. However, there was no significant difference in high-grade tumors between the two groups.

Men taking dutasteride were almost twice as likely to have aggressive prostate cancer if their PSA levels rose, compared to men whose PSA levels went up while taking a placebo. In men with any increase in PSA, aggressive, high-grade tumors were diagnosed in 13.2 percent of those on dutasteride and 7.7 percent of those taking a placebo.

Even a slight rise in PSA levels was a more accurate predictor of aggressive tumors. Among men whose PSA levels increased one point or less, 10.3 percent of those taking dutasteride had aggressive cancer, compared with 5.4 percent taking a placebo.

That trend also held for larger increases in PSA levels. Among men whose PSA levels rose two points or more, nearly 20.9 percent of those taking dutasteride had aggressive cancer, compared with 9.8 percent taking a placebo.

In contrast, PSA levels tended to decrease or remain stable in men taking dutasteride who either had low-grade tumors or no cancer at all.

The study's authors do not suggest that men take dutasteride just to get a more accurate readout of PSA levels attributable to cancer. "However, men who are taking dutasteride can be confident that the drug does not weaken the ability of PSA to find cancer if it develops," Andriole says. "Rather, the drug enhances the ability to find cancer if PSA levels are rising."

More information: Andriole GL, Bostwick D, Brawley OW, Gomella L, Marberger M, Montorsi F, Pettaway, Tammela TLJ, Teloken C, Tindall D, Freedland SJ, Somerville MC, Wilson TH, Fowler I, Castro R, Rittmaster RS. The effect of dutastride on the usefulness of prostate specific antigen for the diagnosis of high grade and clinical relevant prostate cancer in men with a previous negative biopsy: Results from the REDUCE study. Journal of Urology, January 2011.

Provided by Washington University School of Medicine

Prostate cancer screening still unproven: report

NEW YORK, 04 july 2009- PSA blood tests are often used to screen men for prostate cancer, but there is still no good evidence that they cut death rates from the disease, a new review finds.

Based on two recent major clinical trials, the practice of routinely screening men with the PSA test has "at best" a small effect on deaths from prostate cancer, according to the review, published in CA: A Cancer Journal for Clinicians.

The studies, which came out earlier this year in The New England Journal of Medicine, appear to bolster the positions of the American Cancer Society (ACS) and other major medical groups, which do not recommend routine PSA screening for symptom-free men at average risk of developing prostate cancer.

PSA, or prostate-specific antigen, is a protein produced by the prostate gland, blood levels of which generally rise when a prostate tumor is present. PSA blood tests can catch the cancer in its early stages.

But while use of the test has led to more prostate cancer diagnoses, it has done little to nothing to actually cut death rates from the disease, according to the researchers on the new review, led by Dr. Otis W. Brawley of the ACS.

In one of the recent trials, U.S. researchers found that among more than 38,000 men between the ages of 55 and 70, annual PSA screening was no more effective than less-frequent screening at cutting prostate cancer death rates.

The second study, of 182,000 European men, found that PSA screening every few years was associated with only a modest reduction in death risk.

The central problem with prostate cancer screening is that most prostate tumors are slow-growing and would not be deadly even without treatment. So screening can lead to unnecessary treatment of cancers that would never had been life-threatening.

Because prostate cancer treatments, such as surgery and radiation, can have side effects -- incontinence and erectile dysfunction, for instance -- it is possible to do many men more harm than good by treating small tumors.

Researchers are continuing to study ways to refine prostate cancer screening, Brawley and his colleagues point out. That includes measuring "biomarkers" other than PSA that may be able to not only signal the presence of tumors, but also indicate whether they are aggressive and require immediate treatment.

Until then, the researchers say, men should talk with their doctors about whether PSA screening is a good idea. A man's personal risk factors for the disease -- including his family history of prostate cancer -- are key in that decision, according to Brawley's team.

The ACS recommends that most men discuss the possibility of PSA screening with their doctors starting at age 50. Men who are at relatively higher risk -- including those with a brother or father who developed prostate cancer before the age of 65 -- can have that talk after age 40. PSA screening is not generally recommended for men age 75 and older.

SOURCE: CA: A Cancer Journal for Clinicians, July/August 2009.

Will Older Men Give Up the PSA Test?

06 aug 2008--Men ages 75 and older should not be screened for prostate cancer. This is the important and definitive conclusion of the U.S. Preventive Services Task Force, which for the first time has made a specific recommendation about the value of screening for prostate cancer.
To many doctors, the new guidelines will not come as a shock. Quite a few believe that because prostate cancer often progresses slowly, not causing symptoms for 10 years or longer, it’s inappropriate to look for it in healthy older men. A man aged 75 or older may well die of another cause long before his prostate cancer becomes a problem. And treatment of prostate cancer has significant drawbacks, often leading to impotence, incontinence and a variety of other complications that reduce a patient’s quality of life.
But what doctors know and what happens in practice often are two different things.
Prostate screening involves a simple blood test to check for prostate-specific antigen, or PSA. Many doctors find it easier just to do a PSA test than take the time to explain the pros and cons to a patient. Patients themselves, many accustomed since their late 40s or early 50s to getting tested, aren’t always comfortable with the idea of stopping the screening once they reach older age.
And interestingly, doctors say the wives of many older men, themselves firm believers in screening for cervical cancer and breast cancer, sometimes push their husbands and doctors to continue screening for prostate cancer.
The statistics on inappropriate screening are surprising. In one study of 600,000 men treated by the Veterans Administration, screening rates were 64 percent for men ages 70 to 74, 56 percent for men ages 75 to 80, 45 percent for men ages 80 to 84 — and a surprising 36 percent for men ages 85 and older.
“For some men, it’s a tough issue to face,'’ said Dr. Ned Calonge, chairman of the task force and chief medical officer of the Colorado Department of Public Health and Environment. “It isn’t that we know when you’re going to die, or that it’s all over so don’t worry about anything else…. We’re very poor at predicting how much longer you’re going to live. If you take it from the standpoint of risk versus benefit, the chances are more that screening is going to harm you.'’
Dr. Calonge hopes the new guidelines will trigger another round of discussion about PSA testing between doctors and patients.
“Even before this, we were really trying to recommend to physicians that given the uncertainty about benefit for screening, you should really discuss on an individual basis the pros and cons of screening,'’ Dr. Calonge said. “What we find in practice is that adds additional time and effort that’s not compensated as part of normal clinical care. It’s easier to just draw the blood test. I think what we hope now is that it will be just as easy to not do the blood test.'’
What do you think? Will you be ready to give up PSA testing when you or your spouse reaches the age of 75? To learn more about the new guidelines, click here to read the full story. Then join the discussion by posting your comments below.

Why Obese Men Post Lower PSA Levels

By Randy DotingaHealthDay ReporterTue Nov 20, 5:03 PM ET
TUESDAY, Nov. 20 (HealthDay News) -- In recent years, doctors have learned that they need to adjust the results of blood tests to properly diagnose prostate cancer in obese men, but now researchers think they know why.
It turns out that larger men have more blood, which dilutes the levels of the protein called PSA -- a key indicator of prostate trouble.
The new study doesn't definitively prove why overweight and obese men with prostate cancer tend to score lower on the PSA (prostate specific antigen) test, but it does give doctors an idea about what may be going on, said study co-author Dr. Stephen Freedland, an assistant professor of urology and pathology at Duke University.
"PSA is not a bad test for obese men. We just need to know how to use it," he said. "If we use it correctly, it will be just as good as in normal-weight men."
Prostate cancer strikes one in six men, mostly those over the age of 65, according to the Prostate Cancer Foundation.
Older men often routinely undergo a PSA blood test that looks for an antigen made by the prostate that helps it function. The antigen leaks into the bloodstream at a steady rate, and the amount is higher in men with prostate cancer, Freedland explained.
Recent research has revealed that PSA levels are 20 percent to 25 percent lower in overweight and obese men than in men of normal weight. This can translate into diagnostic problems with bigger men, Freedland said.
"You may call him normal and not worry about him and wait another year or two or longer, and that gives time for the cancer to grow," he noted.
According to Freedland, it's not clear if there's any impact on PSA levels from being underweight.
In the new study, researchers tested a theory that the reason PSA levels are lower in larger men is because the antigen gets diluted in larger volumes of blood. "It's like taking a little bit of a drug and putting it in a cup of water versus a bowl of water," Freedland said.
The study authors looked at the records of about 14,000 men with prostate cancer who underwent removal of their prostates between 1988 and 2006. The findings are published in the Nov. 21 issue of the Journal of the American Medical Association.
The researchers found that men who were fatter had larger blood volumes, which the study authors said supports their theory that dilution caused their PSA levels to lower.
The same thing could hold true for blood markers of other cancers, Freedland said. "As we develop blood tests for other cancers, we should be keeping this in mind," he added.
However, Dr. Nelson Stone, a clinical professor of urology and radiation oncology at Mount Sinai School of Medicine, is skeptical of the results, because the research just focused on men with advanced prostate cancer. That and other factors may have skewed the results, he said.
"I don't think they've proved their point," he said. But he added, "We need to be a little bit more careful when we evaluate a patient who is larger, and we look at his PSA and compare to a patient who is thinner. The PSAs are not the same."
More information
For advice on losing weight, visit the U.S. Food and Drug Administration.