Table of Contents

Chapter 5: "Secondary" Local Treatment

a. PSA as a Marker for Disease Progression

As we discussed earlier, 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.

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 > 0.3 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.