The dilution factor

Now there is yet another complicating element at play: BMI and the so-called “dilution factor.” Last year, Dr. Partin and colleagues reported in the Journal of the American Medical Association (2007;298:2275-2280) that the heavier men they tested had more blood volume in which to dilute PSA.

“We were missing cancers because the tests were coming back normal, but in fact this cancer was producing an antigen that we couldn’t measure as being abnormal because it was diluted out in so much more blood,” Dr. Partin explains. “People are beginning to talk about correcting the blood test for volume—for this so-called dilution factor.”


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The continual lowering of the bar for “normal” means urologists are doing more and more advanced testing on people based on lower and lower PSA values. “Now we’re detecting more cancers, but maybe we don’t need to treat all of them,” says Dr. Partin, who refers to his Johns Hopkins partner Dr. Carter as a leader of the increasingly popular watchful-waiting strategy, now widely referred to as active surveillance.

“Some cases of prostate cancer are no worse than having bad diabetes: If you take care of yourself and you watch it and don’t let it get away from you, you’ll probably live as long as you would have without the disease.”

“You have to start someplace”

All the refinements made in the search for hitting on the most actionable PSA values may have complicated things more than simplified them. Yet overall, Dr. Catalona and his team announced, PSA serum measurements were indeed an effective means of detecting prostate cancer; the U.S. age-adjusted prostate cancer death rate has fallen by 37%.

As for the twists and turns along the way, Dr. Catalona sums them up this way: “You can look at the numbers and perhaps see that a value of 4 was a pretty good place to draw the line; it’s going to detect most of the early cancers. There will be a few false positives and some cancers will be missed, but on balance, it was a good place to start. You have to start someplace, but then you absolutely have to keep an open mind that it may not be the best way to go.”

Dr. Partin echoes that view. “We’re beginning to understand how to detect those cancers and follow them. Part of that is [related to] this whole understanding of what’s normal for this blood test and how it changes with time,” Dr. Partin says.

“The PSA test was worked out in the early 1980s. We’ve learned a lot from it, and it’s still hanging on.” Of all the markers available for cancer, he added, PSA as a marker for prostate cancer is the most reliable.”