April 18, 2014

   A Publication of the James Buchanan Brady
   Urological Institute Johns Hopkins Medical Institutions

Volume VI, Winter 2003


The Partin Tables:
Bigger and Better Than Ever

Alan Partin: The latest tables reflect the good news in prostate cancer diagnosis, and the huge improvement in cancer control.



For men with prostate cancer, urologist Alan Partin is a household name, right up there with Donald Gleason, the pathologist for whom the grading system for prostate cancer is named. Partin’s ability to make sense out of numbers—specifically, a man’s PSA, Gleason score, and estimated clinical stage—has allowed thousands of men worldwide to benefit from “virtual surgery,” by predicting what would be found if the prostate were removed surgically, and examined by a pathologist.

The Partin Tables were developed at the Brady Urological Institute in 1993 by Partin and urologist-in-chief Patrick Walsh, after Partin studied the course of prostate cancer in hundreds of Walsh’s radical prostatectomy patients. The tables correlate those three key pieces of the prostate cancer puzzle with the actual pathologic stage, determined when pathologist Jonathan Epstein, M.D., examined the surgically removed prostate specimens. With 95-percent accuracy, they predict a man’s likelihood of being cured by treatment. In the span of a few years, these tables have become indispensable for many patients as well as doctors trying to chart the right course of treatment in a sea of confusing choices. To give you an idea of their importance as a layman’s tool, a recent Google search on “Partin Tables” turned up 1,220 entries on the Internet in English alone. (For this and other work, Partin recently was awarded the prestigious Golden Cystoscope Award by the American Urological Association.)

Now, the tables are bigger and better than ever. The 2001 Partin Tables are based on the results of 5,079 men who underwent surgery at the Johns Hopkins Hospital between 1994 and 2000, and they reflect the huge improvement in cancer control that has come with increasingly early diagnosis. They’re also more consistent; while earlier Partin Tables had included patients from other hospitals, these don’t. Now, “the numbers are sufficient at Johns Hopkins alone to create and validate the results.”

The 2001 tables are broader, too, reflecting the good news in prostate cancer diagnosis. Earlier versions of the Partin Tables divided PSA into broad ranges: 0-4, 4-10, 10-20, and higher than 20. “But because of early detection, the disease is changing,” says Partin, M.D,. Ph.D., Bernard Schwartz Distinguished Professor of Urologic Oncology. “More men are coming in with cancer still confined to the prostate, and over 80 percent of them have a PSA score that is between 4 and 10. We had to offer a better breakdown with respect to PSA points.” The 2001 tables also include two categories for Gleason 7. This is because, Partin explains, “we’ve learned that not all Gleason 7 cancers are alike.”

Briefly, the Gleason score is an equation involving five specific patterns of cancer-cell architecture, called grades. Pathologists add the number of the most common pattern to the second most common pattern and use this score, such as 3 + 3 = 6, to assess the aggressiveness of prostate cancer cells. When a man has Gleason 7 cancer, one part of the equation is a 3 and the other is a 4, which means it’s more aggressive. But there is a difference between Gleason 3 + 4, where most of the tumor is Gleason grade 3, and Gleason 4 + 3, where more of the tumor is Gleason 4. “We now know that Gleason 4 + 3 tends to act more like a Gleason 8, but Gleason 3 + 4 tends to act more like a Gleason 6,” says Partin.

Click here to view the Partin Tables


Partin envisions one day being able to give each man a specific PSA breakdown— “like a bar code on a can of baked beans,” or a PSA profile, like a cholesterol profile, of good and bad PSA.


On the Horizon: PSA Profiling
If the Partin Tables are the next best thing to having surgery and knowing the result, the wonders Partin and colleagues are performing with the prostate-made enzyme PSA may make this simple blood test the next best thing to a crystal ball.

Imagine you got the ultimate Swiss Army knife for Christmas, with more blades and gizmos than you could count, and all day long you kept saying, “Wow, it does this! And this! And this!” That’s what PSA (prostate-specific antigen) has been for scientists studying prostate cancer— the gift that keeps on giving. The more they study it, the more they learn about the chemistry of the prostate, and the many sophisticated biochemical signals it sends out all the time.

“We’re getting to understand PSA a lot better,” says Partin. “It used to be, all we knew was that if your PSA was above 4, your chances were one out of four that you had cancer. We were performing biopsies on everybody with a PSA over 4—but that was acceptable, because we needed to find those cancers. Then, along came free PSA.”

Chemically speaking, a PSA molecule is like a tiny pair of sharp scissors, and its main job is to break down coagulated semen after intercourse, chomping “like a little Pac Man,” as Partin describes it. But PSA also appears in the bloodstream—and it would be disastrous to have millions of these tiny scissors clanking around in the blood, each pointed blade slicing tissue to ribbons. Fortunately, the body is smarter than that: PSA is usually packed in a protective case—a chemical straitjacket, which keeps it from harming innocent tissue. In this form, PSA is “bound”—tied to other proteins, rendered harmless. But sometimes, PSA inactivates itself. In this case, it’s like a pair of scissors with one broken blade. These scissors don’t fit into the case anymore, but that’s okay because they don’t need it; they are chemically passive. This form of PSA is called “free.” With its wings clipped, it flutters freely in the bloodstream, causing no harm.

When a man gets a regular, or “total PSA” blood test, both of these forms are lumped together—the dangerous scissors in the case, and the ones with the broken blade. But in recent years, scientists have developed assays sensitive enough to isolate and quantify both bound and free forms of the PSA molecule, and this separation of PSA can help men in two important ways. It can make the PSA test more specific, and it can help determine how aggressive a man’s cancer is. Patrick Walsh explains it this way: “The higher the free PSA, the more likely that you are free of cancer.” Men with prostate cancer are more likely to have low levels of free PSA.

“The free PSA test allowed us to spare 20 percent of unnecessary biopsies in men with PSA between 4 and 10,” says Partin, “but then the plot thickened. We found that 18 percent of men with PSA between 2.5 and 4 had cancer. So we had to come up with a better test, or better ways to use PSA to predict prostate cancer,” in men with low PSA readings, because “it’s just not fathomable to biopsy every man.”

Radical Prostatectomy and the Probability of Cure

As the new Partin tables show, prostate cancer is being diagnosed earlier than ever. The detection of advanced cancers has gone down 18 percent since 1991—to the point where today, only about 8 percent of men who are diagnosed with prostate cancer are found to have distant metastases.

The great gift of PSA testing is that it has bought us time. On average, prostate cancer is now diagnosed five years earlier than it used to be, when it had to be large enough for a doctor to feel in a rectal exam—or worse, when it caused symptoms such as urinary retention, because it had grown big enough to interfere with the urethra, or back pain, because it had already spread to the bone.

This five-year lead time—plus the increasing success of radical prostatectomy (see story, front page)—has dramatically shifted the window of curability for most men. The good news is that today, most men diagnosed with prostate cancer can be cured with surgery.

We can now divide men who undergo radical prostatectomy into four risk groups, based on their pathologic stage:

Group I. These men have an excellent chance of having an undetectable PSA at 10 years. They have a Gleason score of 6 or lower, organ- or specimenconfined disease, with or without capsular penetration (there is no difference), and negative surgical margins. At 10 years, the likelihood of having an undetectable PSA is 95 percent.

Group II. These men have a good probability of having an undetectable PSA at 10 years. They have a Gleason score of 6, with positive surgical margins, or a Gleason 7 with organ- or specimen-confined disease. At 10 years, the likelihood of having an undetectable PSA is 72 percent.

Group III. These men have a moderate probability of having an undetectable PSA at 10 years. They have a Gleason score of 7 with capsular penetration and positive margins, or Gleason 8-10 disease or positive seminal vesicles. The probability of an undetectable PSA at 10 years is 41 percent.

Group IV. These men have a low probability of having an undetectable PSA at 10 years. They have cancer in the lymph nodes. Yet, at 10 years without any treatment other than surgery, 13 percent have an undetectable PSA.

Of the men who underwent radical prostatectomy at Johns Hopkins in 2000, 70 percent were in Group I, 20 percent were in Group II, 5 percent were in Group III, and fewer than 1 percent were in Group IV.

Partin has been studying two newly discovered subgroups of free PSA , which he believes will become part of the prostate cancer-diagnosing arsenal within the next few years. One of them is called BPSA, for benign PSA—because it’s primarily made by the cells in the center (called the “transition zone”) of the prostate, where benign enlargement occurs, and where cancer rarely begins. BPSA is strongly linked to BPH (benign prostatic hyperplasia, commonly called enlargement of the prostate). The other is called pPSA, for “pro-PSA,” because it’s been identified as the proenzyme, or precursor form of PSA. This pro- PSA—which appears truncated, like a sawed-off shotgun—is a storm cloud, an early warning signal associated with cancer. “When any cell in the body makes a protein, it generally gets a tag, or flag, put on it,” Partin explains. In this case, the chemical pennant that should be attached to the pPSA molecule is a piece of peptide. “When this flag gets put on PSA, you have an active, good working form of PSA.” But without it, “the molecule is inactive. It won’t work as PSA, but it also won’t be bound up by other proteins.” As a result, these little pieces of pPSA flotsam are left adrift in the bloodstream—and learning how to read them, as Partin has been doing over the last few years, may give more specific evidence that a man with low PSA and no other signs of cancer needs to have a biopsy.

“Free PSA is important, but knowing how it’s further fractionated—how much of it is benign, how much of it is not— means we can better detect who does and does not have cancer, especially in the low ranges of PSA,” says Partin. “By itself, the serum BPSA is unlikely to tell us whether a man has BPH instead of cancer, because prostate cancer and BPH frequently coexist. However, in combination with pPSA immunoassays, BPSA may give us additional discrimination.

“PSA should not get into your bloodstream,” Partin continues, “and when it does, it should be in low concentrations. If you have too much of it floating around, is it the good or the bad—and that’s where we start breaking it down. Is it benign free PSA, or pro free PSA?” Partin envisions one day being able to give each man a specific PSA breakdown—“like a bar code on a can of baked beans, or a PSA profile, like a cholesterol profile, of good and bad PSA.”

Partin has developed blood tests to measure these new forms of PSA, working with Hybritech-Beckman, and about 300 men have been tested so far. He gives credit to the many Brady patients who have helped this research by donating their blood. “Without them, we couldn’t have done what we’ve done. The blood they donated has gone to the development of new tests. Our patients helped us do this.”

 

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