A Prostate Cancer Revolution?

Prostate cancer is the second leading cancer killer among men, after lung cancer. The American Cancer Society projects that in 2007 there will be 219,000 new cases and 27,000 deaths. Yet detecting the disease early has always been problematic. The only blood test available now—a test for prostate-specific antigen (PSA)—is not good at distinguishing malignancies from benign prostate enlargement (BPH). And it's useless for separating aggressive cancers from others that are so slow-growing they will likely never cause problems.

But a new blood test, described this week in the journal Urology, could change all that. In a study of 385 men, the new test was able to distinguish BPH from prostate cancer, and it pinpointed men who were healthy, even when their PSA levels were higher than normal. It also did the reverse—singling out men with cancer, even when their PSA levels were low. It may also distinguish cancer confined to the prostate from cancer that has spread beyond the gland. And it has the potential to dramatically reduce the number of biopsies performed every year. More trials are required, but if they're as promising as this initial study, the new test could reach the market in two to three years. NEWSWEEK's Anne Underwood spoke with the study's senior author, Dr. Robert Getzenberg, director of urology research at Johns Hopkins University School of Medicine. Excerpts:

NEWSWEEK: Why is the PSA test so problematic?
Robert Getzenberg:
In the 25 years we've been using it, the PSA test has changed the face of prostate-cancer treatment. When I started in this field, half of patients had their cancer detected when it had already spread outside the prostate. Today we're finding cancer earlier, which is reducing mortality. But the test is problematic because PSA itself is not related to cancer. It's a protease [an enzyme that chops up proteins]. It's made by the prostate to keep the consistency of the ejaculate right, which is important. PSA may also protect against viral or bacterial invasions. But the prostate gland with cancer doesn't make any more PSA than the normal prostate. The levels are elevated because the PSA is not going into the ejaculate where it's supposed to go. Instead, it's going into the bloodstream, because cancer makes the prostate gland more leaky.

How is your test different?
It's a test for a structural protein found only in the nucleus of prostate-cancer cells, called early prostate cancer antigen-2, or EPCA-2. We don't know its exact function, but it's not expressed at all in normal cells. We think it gets into the blood through cell breakdown. Once it gets into the blood, it's very stable and hangs around a long time.

Does the level in the blood vary with the severity of the condition?
There are clear differences in levels between men who are healthy, those with BPH, those with cancer that's confined to the prostate and others whose cancer that has spread.

You studied men before and after prostate surgery. How did the levels change after surgery?
On average, six months later, the levels were at zero. Whatever caused the elevated EPCA-2 was removed.

How reliable is the test? Did you get any false positives?
About 3 percent of the time, when the test was positive, there was no prostate cancer there. In 6 percent of cases, there were false negatives [meaning the test came out negative but the patient did have cancer].

Still, that's much better than the situation today, where men with elevated PSA levels go for biopsies, which 80 percent of the time turn out negative.
An estimated 1.3 million to 1.6 million men undergo biopsies every year to identify the 230,000 or so patients with cancer. We're clearly overbiopsying.

And unless you stick the biopsy needle right into the tumor site—in other words, if you hit a part of the prostate without cancer—the biopsy will come out negative.
Doctors use ultrasound to guide the needle, but many lesions aren't visible by ultrasound. Often, they're very small. That's why doctors perform 12 core biopsies per patient—that means 12 needles. Some do 18 or more. You're looking for the equivalent of microscopic lesions inside a peach. Sometimes you hit it, sometimes you don't.

I never realized it before, but that means biopsying for breast cancer is easier. You start with a mammogram that shows the precise location of the suspicious lump.
Breast cancer lesions are typically bigger and easier to visualize on imaging. They are sometimes multifocal [found in multiple locations], but not as frequently. In prostate cancer, on average, you have five to six lesions. The prostate is also less accessible.

So if future trials go as well as this one, the EPCA-2 test could potentially revolutionize prostate care.
It will be the tool for identifying men with prostate cancer and separating them from others with BPH and prostatitis [inflammation or infection of the prostate]. It will identify the group that needs aggressive therapy from those who can use watchful waiting. Now, because we don't know which cancers are aggressive and which are indolent, we're overtreating some patients and undertreating others.

Do you see this test being used in conjunction with the PSA test?
Initially, yes. There's lots of work to do before we're ready to throw out the PSA. Eventually, if doctors find that the PSA test doesn't add much, they may decide they want to use EPCA-2 alone.

Do you foresee every man over 40 getting this test one day?
Yes, there's a window when cancers are curable. You want to catch them early. I would say men should start in their 40s, because that would establish the baseline, the normal level. How it changes over time is instrumental.

How exciting is this?
We've had the data for more than a year. We've been going over every aspect of it again and again, because it's almost too good for us to believe