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PSA as a Marker for Disease Progression

When it comes to assessing disease progression, PSA is widely accepted as an invaluable tool.

PSA is produced by all prostate cells, not just prostate cancer cells. At this point in your journey, your cancer cells have either been removed or effectively killed after being bombarded with radiation. But some cells might have been able to spread outside the treatment areas before they could be removed or killed. These cells at some point begin to multiply and produce enough PSA that it can again become detectable by our lab tests.

Therefore, PSA is not really a marker for disease progression, but a marker for prostate cell activity. Because the two correlate well after initial treatment for local therapy, tracking the rise of PSA in this setting is an important way of understanding how your prostate cancer is progressing.

However, in order to determine whether your PSA is rising, you need to first determine where it is rising from. Often, imaging tests will not be able to determine this when the PSA is at very low levels. Tests such as bone scans, Prostascint scans, and CT/MRI scans in this setting are often negative and thus most decisions on the next therapy (ie radiation or hormonal therapy) are based on probabilities of cure with radiation rather than by seeing the cancer on scans. Prostascint scans in this setting are often not very helpful, given their high false positive and false negative rates, and thus can be misleading.

After prostatectomy, the PSA drops to "undetectable levels," typically given as < 0.05 or < 0.1, depending on the lab. This is effectively 0, but by definition we can never be certain that there isn’t something there that we’re just not picking up. By contrast, because normal healthy prostate tissue isn’t always killed by radiation therapy, the PSA level doesn’t drop to 0 with this treatment. Rather, a different low point is seen in each case, and that low point, or nadir, becomes the benchmark by which to measure a rise in PSA.

Because the starting point is different whether you had surgery or radiation therapy, there are two different definitions for disease recurrence as measured by PSA following initial therapy.

In the post-prostatectomy setting, the most widely accepted definition of a recurrence is a PSA > 0.2 ng/mL that is seen to be rising on at least two separate occasions at least two weeks apart and measured by the same lab. In the post-radiation therapy setting, the most widely accepted definition is a PSA that is seen to be rising from nadir in at least three consecutive tests conducted at least two weeks apart and measured by the same lab. It’s important to always use the same lab for all of your PSA tests because PSA values can fluctuate somewhat from lab to lab.

The reason that we need to look for confirmation from multiple tests following radiation is that the PSA can "bounce" or jump up for a short period after radiation therapy, and will then come back down to its normal level. If we relied only on the one elevated PSA, it’s possible that we will have tested during a bounce phase, and the results will therefore be misleading. This PSA bounce typically occurs between 12 months and 2 years following the end of initial therapy.

If your PSA is rising but doesn’t quite reach these definitions, your doctor might be tempted to start initiating further therapy anyway. Remember that PSA is only one of many factors that help to determine your prognosis after treatment. The original clinical stage of disease, your pre-diagnostic PSA, and your overall health and life expectancy are also key factors in assessing the aggressiveness of your disease, so be prepared to discuss treatment options even if you don’t fit the classical categories for PSA rise after initial therapy.

On the other hand, if your PSA is rising and you do fit the categories defined above, that doesn’t necessarily mean that your situation is dire. What researchers have been finding over the past few years is that universal PSA cut-offs might not be sufficient for truly understanding how prostate cancer grows.

PSA Velocity

Suppose one man underwent intensity-modulated radiation therapy (IMRT), and his PSA nadir was 0.15 ng/mL. Over the course of nine months, it slowly creeps up until it hits 0.45. But his brother, who also underwent IMRT, nadired at 0.32 ng/mL. If after the same progression over the course of nine months his PSA also rose to 0.45, are they now in the same place? Or is there some significance to the fact that one man’s PSA rose much more rapidly than his brother’s?

The rate at which your PSA rises after prostatectomy or radiation therapy can be a very significant factor in determining how aggressive your cancer is, and can therefore be useful in determining how aggressively it might need to be treated.

When looking at PSA velocity in a few hundred men who had undergone either prostatectomy or radiation therapy, researchers found that men whose PSA doubled in under three months had the most aggressive tumors and were more likely to die from their disease, whereas those whose PSA doubled in more than ten months had the least aggressive tumors and were less likely to die from their disease.

If we go back to our two hypothetical cases, although both have a PSA of 0.45 ng/mL, the first one, whose PSA rise represents a doubling within nine months after treatment, would likely be considered for an aggressive therapeutic regimen. And the second case with the smaller rise in PSA? He might be watched closely to see how rapidly his PSA rises, and to determine when it might be time to intervene.

However, PSA doubling time or velocity does not always remain the same over time. So even if you have a very slowly rising PSA now, continued monitoring with your doctor is important. Also, if you’ve consistently kept to a very low PSA rate after treatment, any rise will likely be seen as a signal that the tumor might be starting to grow again.

Measuring and using PSA velocity is an art, not a science. There’s no magic number of times that your PSA has to be tested in order to determine the rate of rise, although most researchers would agree that more frequent tests over longer periods of time will likely give a better sense of how your tumor is growing.

Ultimately, PSA is only one of many factors that can influence the decision to pursue additional treatments. You and your doctors will need to weigh all of the different factors before deciding on the course that’s right for you.

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