No one likes going for that annual physical exam. For many, the anxiety increases when it includes a cancer screening.

For men, that fear can go up a notch when their exam includes a PSA -- the screening for prostate cancer. While once believed to revolutionize the diagnosis of this disease, today the PSA is at the center of debate, frequently charged with leading to unnecessary treatment as well as causing unnecessary anxiety.

"It's a controversial arena -- the PSA is a marker of prostate bulk and size, but it's highly expressed in benign prostate disease as well as cancer -- so in that context it's not a specific marker," says prostate cancer researcher Arul Chinnaiyan, MD, PhD, the S.P. Hicks Collegiate Professor of Pathology at the at the University of Michigan Medical School.

As a result, he says, a PSA score can not only frighten a man unnecessarily, but also lead to overtreatment -- including unnecessary biopsy and even surgery.

"[The PSA] is responsible for hundreds if not thousands of unwarranted biopsies a year, and ultimately overtreatment of incidental [cancers]," says Chinnaiyan.

Moreover, a recent study from the Yale School of Medicine and the VA Connecticut Healthcare System found no evidence that a PSA screening could improve the survival rates of men diagnosed with prostate cancer -- leading many to wonder if the test is even necessary at all.

At the same time, however, prostate specialists like NYU's Herbert Lepor, MD, remind us that not having this test can mean missing an early prostate cancer, and ultimately losing your life.

"People forget that you can die from this disease. Prostate cancer can kill you and right now the PSA is an important way to determine what your risk of dying of prostate cancer is, and hopefully allow you to take steps to reduce that risk," says Lepor, chairman of urology and professor at the NYU School of Medicine in New York.

Indeed, new statistics released by the American Cancer Society (ACS) show that the rate of death from all cancers has declined, suggesting that better screening tools is one reason, particularly in the case of prostate cancer.

And while Lepor acknowledges that sometimes the PSA does lead to an unnecessary biopsy -- and even unnecessary surgery -- still, he says, it's not a screening a man should routinely ignore.

"What you ultimately end up with here is the risk of overtreatment versus the risks of dying from prostate cancer," says Lepor, "and I think most men would rather not die."

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Understanding Prostate Cancer and the PSA Exam

The prostate gland is a small walnut-sized organ that sits in a man's pelvis, right behind the pubic bone. The bladder lies just on top; the rectum, just below. The urethra, the tube that carries urine out of the body, runs through the prostate gland, and on either side is a network of nerves that help control sexual function.

The role of the prostate is to produce a substance that mixes with sperm to create semen. Prostate cells also secrete a number of proteins, including prostate specific antigen, or PSA.

"It's important to note that both normal prostate cells and malignant prostate cells produce PSA," says Chinnaiyan.

So how does the PSA relate to prostate cancer?

Experts say a small amount of PSA is always leaked into the bloodstream. Just how much is found in the blood is then used to determine the risk of prostate cancer.

While it seems like a straightforward association, it's not. The reason: According to urologist Simon Hall, MD, there are some men with a very aggressive prostate cancer whose PSA levels are normal. Likewise, there are men whose PSA levels are soaring but who are cancer-free. And right now, no one is sure why.

Still, he tells WebMD, "It's important for men to understand that the PSA does not diagnose cancer; it helps to create a risk profile. It only tells you if your risk is increased," says Hall, chairman of the department of urology at the Mount Sinai School of Medicine in New York City. And, he says, when interpreted properly, it can do just that.

To help further define those risks, doctors frequently perform a second exam known as the DRE or digital rectal exam. In this test the doctor manually examines the prostate through the rectum, checking for shape, symmetry, hardness, and size.

The Prostate Cancer Biopsy: Your Ultimate Diagnostic Depending on the findings of both the DRE and PSA screenings, the final diagnostic step is frequently a biopsy or sampling of the cells inside the prostate. In this procedure, Lepor says, 12 to 14 cores [cell samples] are removed and tested for the presence of cancer cells and their type, size, and aggressiveness (how fast they are growing).

The method of notating this measurement is called the Gleason score, and it ranges from 2 (known as an incidental cancer and probably slow growing) to 10 (which indicates a highly aggressive cancer with imminent health threats).

But as effective as the biopsy can be in determining both risks and treatment choices, Lepor points out that it doesn't always render clear-cut results.

"It's entirely possible for the sampling to pull up cells that indicate only a moderate or even incidental cancer when right next door there could be more aggressive cells," he says.

If the decision is then made to remove the prostate, and no more aggressive cells are found, then the surgery might have been unnecessary. But at the same time, he says, not doing the surgery -- and missing the aggressive cells -- could mean death.

But rather than blame the PSA for the unnecessary procedures, both Hall and Lepor say it can aid in making the right treatment decision.

"While the PSA does not yield a cancer diagnosis on its own, together with other pieces of information it forms a risk profile, and it is that risk profile that can be very important when determining an individual man's course of treatment," says Hall.

To Screen or Not In fact, despite controversy, most doctors agree the PSA remains an important and necessary diagnostic tool.

In addition to the ACS report, Hall adds that "there is no question that since the PSA era the two things that have changed are fewer men are diagnosed with metastatic cancer, and we have seen a decrease in the mortality rate from prostate cancer overall, all because we are picking up the cancers earlier."

The question remains, however, is who needs testing the most, how often, and when? Today, most doctors agree it's a patient-by-patient decision, with only the most flexible guidelines to follow.

One factor that is important for all men, however, is their age. But if you're thinking the older you are, the more you need this test -- guess again.

"The longer your life expectancy, the more important it is to find a prostate cancer early -- so the more important the PSA becomes," says Lepor.

Also important to consider, say experts, is a man's general health. Your life expectancy, says Lepor, should be at least 10 years in order for the PSA screen to be beneficial.

Hall agrees, "The average life expectancy is somewhere around 78 to 80 and most prostate cancer patients live a long time even without treatment. So even if you did find the cancer at that age it's not likely you would do aggressive treatment, so testing is less necessary in men over 70 or 75," he says.

Currently, American Cancer Society (ACS) guidelines recommend doctors offer the PSA blood test and the DRE yearly to men aged 50 with a life expectancy of at least 10 years. Providers should discuss with them the risks, benefits, and limitations of testing. Men at high risk -- including blacks and all men with a close relative who had prostate cancer before age 65 (father, brother, or son) -- should start testing beginning at age 45.

Those men at ultra-high risk -- with several close relatives with prostate cancer at an early age -- are recommended to begin testing at age 40.At the same time, it's important to note that ACS cautions that no major scientific or medical group recommends routine testing for prostate cancer at this time. Instead, they suggest a case-by-case analysis based on each man's individual history.

Says Lepor: "The bottom line is there are no rules set in stone -- every man needs to talk to his doctor about when to start screening and how often, and in the event a cancer is suspected or diagnosed, they need to openly discuss the options of biopsy and ultimately, treatment," says Lepor.

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The Future of Prostate Screening

Two advances that could one day make the PSA obsolete.

In the first advance, Chinnaiyan and his team looked to the body's own immune system for clues about prostate health.

"We are looking at the antibodies or biomarkers produced by the immune system against proteins or protein products made by the cancer cells. We are taking advantage of the body's own immune system activity," says Chinnaiyan.

In studies published in The New England Journal of Medicine in 2005, doctors looked at blood samples taken from 331 prostate cancer patients prior to surgery and from 159 men with no history of cancer.

The result was the identification of a group of 22 biomarkers in the blood of cancer patients that helped identify cancer with good accuracy.

Hall says the study had definite value. "In a controlled setting it was better than PSA or DRE in figuring out who had cancer and who didn't," he says.

Because the test itself is still complicated for the average laboratory, the projected time frame for widespread clinical use is about five years, according to Chinnaiyan.

Closer to coming to fruition is a second advance, also coming from Chinnaiyan's lab in conjunction with researchers at Harvard's Brigham and Women's Hospital in Boston. In this instance the scientists are looking at the way cancer rearranges genes and causes some specific pairs to merge.

In research published in the journal Science, this molecular signature was found to be present in the majority of prostate cancer tissue samples.

Chinnaiyan estimates this test -- which is similar to the genetic tests now in use for breast cancer -- may be available in less than two years.

Says Chinnaiyan: "This goal here is to eliminate unnecessary biopsies -- and these new tests may help us to do that."

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This article was the first of a two-part series. Visit Foxnews.com tomorrow for Prostate Cancer Part II: Best Treatments for Prostate Cancer

By Colette Bouchez , reviewed by Louise Chang, MD

SOURCES: Arul Chinnaiyan, MD, PhD, the S.P. Hicks Collegiate Professor of Pathology, University of Michigan Medical School. Hebert Lepor, MD, chairman, urology; professor, NYU Medical Center, New York. Simon Hall, MD, chairman, department of urology, Mt. Sinai Medical Center, New York. Concato, J. Archives of Internal Medicine, Jan. 9, 2006; vol 166: pp 38-43. American Cancer Society Facts and Figures, February 2006. American Cancer Society: “Overview: Prostate Cancer, Prostate Cancer Information Reference.” Chinnaiyan, A. New England Journal of Medicine; vol 353: pp 1224-1235. Tomlins, SA. Science, Oct. 28, 2005; vol 310: pp 644-648. American Cancer Society Guidelines for Early Detection of Cancer, 2006.