A major milestone in the prostate cancer journey is obtaining a PSA level after treatment. If a man has surgery, a procedure in which the entire prostate gland is removed, the expected result is a permanently undetectable PSA. Because a successful surgery should remove all remnants of the cancer as well as the benign elements of the prostate, there should be nothing left to produce the dreaded PSA. Patients derive a tremendous amount of satisfaction and relief in hearing that there PSA is undetectable, an unambiguous sign that their prostate cancer is gone. For some men, however, the news is not as great. At some point after surgery, 15-40% of men hear the dreaded news that their PSA is not undetectable and that, most likely, there cancer has returned. What many patients do not know is that not all PSA recurrences are created equal. Some types of recurrences are much more worrisome than others and require very different treatment approaches. In this post I will try to define PSA recurrence and attempt to differentiate the different types of recurrences.
Defining a PSA recurrence seems pretty obvious at first glance. After all, PSA after prostatectomy should be 0. Any other number is considered a PSA recurrence. In reality, things are not that simple. First, we have to differentiate PSA recurrence from PSA persistence. A first PSA test obtained 1-3 months after prostatectomy should be 0. However, any PSA value other than 0 is not considered a PSA recurrence at this time. The reason for this is that the PSA has not recurred but, rather, has persisted. Although this difference in terminology may seem like nothing more than semantics, it makes a tremendous difference in terms of prognosis and understanding the status of the prostate cancer. Patient who have a persistent PSA after prostatectomy almost always have metastatic disease. While imaging tests like a bone scan or CT scan may be negative, a persistent PSA indicates that some cancer cells are lurking somewhere in the body that are simply too small to identify on imaging tests. These cells are then labeled micrometastatic disease. Unfortunately, patients in this situation can no longer be considered curable. Instead, they often get palliative hormonal therapy which, fortunately, can often keep those few micrometastatic cancer cells from significantly growing for many years. These patients may also qualify for clinical trials.
Unlike PSA persistence, PSA recurrence occurs when a postoperative PSA at first goes to 0 and then begins to rise after some period of time. However, at least technically speaking, not all rises in PSA have been considered recurrences. Historically, a PSA rise to 0.4 after surgery has been considered a recurrence. Rises in PSA lower than this have been considered insignificant, possible due to some left over benign prostate tissue. More recently, the value of 0.2 has been chosen. Although these definitions seem pretty arbitrary they actually have significance because they determine when the patient has recurrent cancer and, in turn, when they should start salvage therapy. With the advent of ultrasensitive PSA, much lower PSA values have been recorded and some doctors have initiated salvage therapy at PSA levels significantly lower than 0.2.
As I mentioned earlier in this post, a PSA recurrence has different implications on the status of prostate cancer and subsequent prognosis depending on several factors:
1) Time from Surgery: Many studies have demonstrated that the longer the time between surgery and PSA recurrence, the less chance that the recurrent cancer is aggressive and likely to spread. The consensus seems to be that 3 years appears to be a critical cut off point. One study demonstrated that for men with otherwise good risk factors, those that had a PSA recurrence more than 3 years after surgery had a 13% greater chance of surviving their prostate cancer 15 years later as compared to those men with a PSA recurrence within 3 years of surgery( 94% versus 81% survival at 15 years).
2) Gleason Score of Prostate Cancer: The Gleason score is a measure of how aggressive the cells of prostate cancer look under the microscope. It generally ranges from 6-10, with higher scores being associated with more aggressive cancer. Men with Gleason scores above 7 who have a PSA recurrence after prostatectomy are at higher risk for metastasis and death from prostate cancer. For example, a study demonstrated that men with recurrence of a Gleason 8 or higher prostate cancer within 3 years of prostatectomy had a 19% higher chance of surviving their prostate cancer within 15 years than those men with a recurrence of Gleason 6 or 7 prostate cancer within 3 years of prostatectomy( 62% versus 81% survival at 15 years).
3) PSA Doubling Time: The PSA doubling time appears pretty self explanatory. The term refers to the time it takes for the PSA to double in value. To calculate this number you need a few PSA values spread at least 3 months apart. You also need to use a fairly complex formula to get the exact value. For our purposes, a rough, eyeball assessment will do just fine. For example, by looking at a series of PSA values we can roughly estimate if the PSA is doubling every month, every 6 months, or every year, etc... Studies have demonstrated that PSA doubling time is one of the most important prognostic factors used to evaluate a PSA recurrence after prostatectomy. Let’s look at an example: If a man has a PSA recurrence more than 3 years after prostatectomy for a Gleason 6 prostate cancer and his PSA doubling time is more than 15 months, his chance of surviving the prostate cancer at 15 years is 94%. If that exact same man has a PSA doubling time of less than 3 months, however, his chance of surviving prostate cancer at 15 years is only 19%. As you can see, the importance of the PSA doubling time cannot be overstated.
These 3 factors are vital in evaluating a man with a PSA recurrence after prostatectomy not only to determine prognosis but, also, to figure out what future treatment needs to be undertaken, if any. A man with a PSA recurrence more than 3 years after prostatectomy for a Gleason 6-7 prostate cancer and a PSA doubling time of greater than 15 months has a 94% chance of surviving his prostate cancer at 15 years. In contrast, a man with a PSA recurrence less than or equal to 3 years after prostatectomy for a Gleason 8-10 prostate cancer and a doubling time of less than 3 months have <1 % chance of surviving for that same period of time. As you can imagine, most men find their situation somewhere in between these two extreme scenarios.
Men with favorable factors most likely have a local recurrence of the cancer in the part of the pelvis where the prostate was located. This type of recurrence tends to move more slowly and can be cured with radiation therapy with some success. Some men, depending on their overall health and age, may not even need any treatment for this type of low risk recurrence. Men with high risk factors, in contrast, most likely have metastatic disease. This type of recurrence is usually more aggressive and not responsive to local therapy. Instead, men with this type of PSA recurrence are usually treated with palliative hormonal therapy to try to control rather than cure the recurrent cancer. Others may opt for clinical trials to try novel treatments to battle the more aggressive cancer.
The take home message of this post is to NOT treat all PSA recurrences the same. While a PSA recurrence is obviously disappointing and frightening it is not always as bad as you might think. Many recurrences are very manageable and still offer the possibility of cure. Some recurrences may not even need to be treated. Men with PSA recurrence should discuss their specific risk factors with their urologist in determining an appropriate treatment course.
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