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PSA Rising
Last Reviewed: June 09, 2021

When prostate cancer is caught in its earliest stages, initial therapy can lead to a high chance for a cure, with most men living cancer-free for many years. The cancer cells have either been removed with surgery or killed with radiation.

But some prostate cancer cells may have spread outside the treatment areas, or metastasized, before they could be removed or killed. At some point, these cells may begin to multiply and produce enough PSA that it can again become detectable by lab tests.

For more information, including a list of questions to ask your doctor if your PSA is rising after initial treatment, review What to Ask When Your PSA is Rising After Initial Treatment.

If a man previously underwent surgery, his PSA should be undetectable; after radiation, there are often residual normal prostate cells that still make some PSA. PSA monitoring after treatment is an important way of understanding whether or not all the prostate cancer cells have been destroyed.

PSA is produced by all prostate cells, not just prostate cancer cells. In order to determine why your PSA is rising, your doctor will first try to determine where the cells producing PSA are located.

This involves imaging, such as a CT, MRI, or bone scan. However, in cases where PSA is still very low, imaging tests may not provide enough information to determine a further course of action. So sometimes the next steps are based on the probability (chance) of cure with radiation rather than actually seeing the cancer on scans, because the clusters of prostate cancer cells might be very small. Newer molecular imaging scans can be done at select centers; these scans include C11-choline (performed in limited clinic centers), F18-fluciclovine (Axumin; FDA-approved and available across the US), and F18-sodium fluoride (to evaluate for bone metastases).

PSMA-PET is another new molecular imaging technology, initially FDA approved in 2020, that uses PSMA (a protein on the surface of prostate cancer cells) to more precisely identify prostate cancer metastases. It is significantly more sensitive than traditional bone and CT scans.

Understanding PSA Numbers

After the surgical removal of the prostate (prostatectomy) PSA drops to virtually undetectable levels (less than 0.1), depending on the lab performing the PSA test. This is effectively zero, but by definition can never get all the way to zero, given the sensitivity of the test and the fact that, at very low readings, other proteins may be misread as “PSA protein.” In contrast, after radiation therapy, the PSA level rarely drops to zero. This is because normal healthy prostate tissue isn’t always completely killed during radiation therapy. Rather, a different low point is seen in each individual, 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 2 different definitions for disease recurrence as measured by PSA following initial therapy.

Following a prostatectomy, the most widely accepted definition of a recurrence is a confirmed PSA level of 0.2 ng/mL or higher. After radiation therapy, the most widely accepted definition is a PSA that rises from the lowest level (nadir) by 2.0 ng/mL or more. It’s important to try to always use the same lab for all of your PSA tests because PSA values can fluctuate somewhat from lab to lab.

After radiation therapy, doctors need to look for confirmation from multiple tests because PSA can “bounce” or jump up for a short period, and will later return to its low level. If only one test was performed, it’s possible that it could have occurred during a bounce phase, and that the results would therefore be misleading. PSA bounces typically occur 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 initiate further testing to assess the risk that cancer has come back. This is a gray area that requires a lot of input from your team, possibly including your urologist, radiation oncologist and medical oncologist to help you decide on the best course of treatment.

For more information, including a list of questions to ask your doctor if your PSA is rising after initial treatment, download or order a print copy of the Prostate Cancer Patient Guide.

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