What's the risk of dying when prostate cancer comes back after treatment? Two new studies point to who's at high risk and who isn't.

A crucial difference, the two new studies suggest, is how fast blood levels of prostate-specific antigen (PSA) go up.

Anthony V. D'Amico, MD, PhD, chief of genitourinary radiation oncology at Brigham and Women's Hospital and Dana-Farber Cancer Institute, led a study of 358 men who underwent radiation therapy. His team looked at whether prediagnosis changes in PSA predicted a man's risk of dying from prostate cancer. The findings confirmed the results of an earlier study of men who underwent prostate surgery.

"The best use of PSA is not to look at the number but to look at the trend over time," D'Amico tells WebMD.

Stephen J. Freedland, MD, clinical instructor in urology at Johns Hopkins University, led a team that gathered data on 379 men who underwent prostate surgery but had their cancer come back.

"These studies show that looking at changes in PSA are more important than a single value," Freedland tells WebMD. "One PSA result is like looking at a snapshot of a horse race and trying to determine who will win. Looking at snapshots over time gives you a better idea."

Both studies appear in the July 27 issue of The Journal of the American Medical Association.

Read WebMD's "Prostate Cancer Treatment: Long-Term Effects"

PSA Velocity

PSA is a chemical marker on the outside of prostate cells. As prostate cancer cells increase in number, blood PSA levels rise.

But PSA levels in and of themselves aren't a reliable indicator of cancer. Blood levels of PSA go up for other reasons besides cancer. And very deadly prostate cancers can occur even at low PSA levels.

"There has been controversy over what is the best use of PSA as a screening tool and what is the best use of the test as a tool to guide treatment," D'Amico says.

Instead of simply testing once for PSA and deciding that it is "high" or "normal," D'Amico says it appears to be more useful to test at regular intervals. This gives a reading on PSA change — what doctors call PSA velocity.

"Our study shows that men who experience a two-point rise in PSA in the year preceding a diagnosis of prostate cancer — despite a low level of PSA and despite a biopsy showing a supposedly 'favorable' prostate cancer — have more aggressive cancer and need more aggressive treatment to cure it."

Men whose PSA levels rose more than two points in a year had a 12-fold higher risk of dying from prostate cancer than men whose PSA levels rose less quickly.

"The median survival for rapid risers is only six years, and that is very short for prostate cancer," D'Amico says. "The bottom line for patients is this: Get a PSA test annually and know the result. Because even if your doctor isn't looking at year-to-year change, at least you can. We recommend getting a baseline PSA test at age 35, especially for men whose dads had prostate cancer."

Read WebMD's "Study: Prostate Screening Saves Lives"

Zeroing In on Prostate Cancer Death Risk

Many men elect to have their prostate glands removed when they are diagnosed with prostate cancer. With no prostate, their PSA levels should drop to zero. But within 10 years of surgery, more than a third of these men eventually have PSA appear in their blood.

Where does the PSA come from? Prostate cancer cells that have begun to grow again. But that's not always bad news. These recurrent cancers often grow very slowly.

"The nice thing is that a PSA test can identify cancer recurrence years before we would detect it clinically," Freedland says. "But then, it is hard to figure out who has aggressive cancer and who doesn't."

After looking at hundreds of cases, Freedland's team came up with three things that predict which men are likely to have problems:

— How quickly the PSA became detectable after surgery. Men whose PSA came back more than three years after surgery did better than those whose PSA came back in three years or less.

— The most important factor, however, is how fast the PSA goes up. This is the doubling time — how long it took for a PSA of 1 to become 2, and 4, and 8, and so on.

— The Gleason score of the original tumor. Gleason score is based on what a cancer looks like under the microscope. The higher the score, the more aggressive looking the cancer. Men with Gleason scores of less than 8 did better than those with Gleason scores of 8 or more.

"When you put it all together, we are 84 percent accurate in predicting long-term outcome for these men," Freedland says.

For example, the very worst prediction would be a man whose PSA reappeared in less than three years, whose PSA level doubled in less than three months, and who had a Gleason score of more than 8. Such men have a 51 percent chance of surviving for five years, a 1 percent chance of surviving for 10 years, and less than a 1 percent chance of surviving for 15 years.

The best prediction would be for a man whose PSA reappeared after more than three years, whose PSA level took at least 15 months to double, and whose Gleason score was less than 8. Such men have a 100 percent chance of surviving for five years, a 98 percent chance of surviving for 10 years, and a 94 percent chance of surviving for 15 years.

"The significance of the finding is it can help us identify who needs treatment after surgery recurrence and who doesn't," Freedland says.

Read WebMD's "Recently Diagnosed With Prostate Cancer?"

Great Information — but What Can a Man Do About It?

Knowing who is at risk is helpful. But what's missing is knowing exactly what to do about it, says Mitchell S. Anscher, MD, professor of radiation oncology at Duke University Medical Center. Anscher's editorial accompanies the D'Amico and Freedland studies.

"I think the only thing the patient can really take home from this, if they fall into one of the unfavorable categories, is knowing they might not do as well with standard treatment," Anscher tells WebMD. "We cannot yet say whether additional treatment would be more successful — that has to be studied."

D'Amico and Freedland readily admit this is true.

"We identified who needs treatment, now we need to figure out how to treat them," Freedland says. "There is still a lot we need to do. Even if we told a guy, 'You are in trouble,' we still don't know what to do about it. But at least now we have a good handle on who needs the aggressive treatments."

And what would this aggressive treatment look like? Nobody is sure.

"I would in general urge patients to be cautious and not jump to any conclusions from these studies, or seek to change what they would do," Anscher says. "They are good studies, but they are not going to change the standard of care just yet."

By Daniel J. DeNoon, reviewed by Michael W. Smith, MD

SOURCES: Freedland, S.J. The Journal of the American Medical Association, July 27, 2005; vol 294: pp 433-439. D'Amico, A.V. The Journal of the American Medical Association,July 27, 2005; vol 294: pp 440-447. Anscher, M.S. The Journal of the American Medical Association,July 27, 2005; vol 294: pp 493-494. Stephen J. Freedland, MD, clinical instructor in urology, Johns Hopkins University, Baltimore. Anthony V. D'Amico, MD, PhD, chief of genitourinary radiation oncology, Brigham and Women's Hospital and Dana-Farber Cancer Institute, Boston. Mitchell S. Anscher, MD, professor of radiation oncology, Duke University Medical Center, Durham, N.C.