Tuesday, October 27, 2009

The Case for Ultra-Sensitive PSA Testing After Prostate Cancer Treatment

Ultra-sensitive PSA (Prostate Specific Antigen) tests, also known as Hypersensitive PSA test, 3rd Generation PSA test, or Post-Prostatectomy PSA test, have been created specifically for patients treated for prostate cancer to provide early detection of recurrence of cancer. Ultra-sensitive PSA testing is appropriate for men with cancer that produced a rising PSA before treatment, and who currently have a PSA level less than 0.1 ng/ml after treatments such as radical prostatectomy or radiation therapy. The currently available tests generally have a sensitivity of 0.01 ng/ml, versus the more common PSA tests with 0.1 or 0.05 ng/ml sensitivity, so the ultra-sensitive PSA tests are at least five to ten times more sensitive. PSA levels after successful radical prostatectomy surgery are expected to be below 0.05 ng/ml, and thus undetectable by standard PSA testing. Radiation therapy and other prostate cancer treatments may also cause PSA levels to eventually drop to very low levels, but usually not as low, as reliably, or as quickly as surgically removing the prostate.

Ultra-sensitive PSA testing is controversial. Some say it provides too much information and increases PSA anxiety. Some suggest that it doesn't change anything because the doctors won't recommend considering secondary treatment until the PSA level reaches 0.2 to 0.5, or perhaps even higher.  There also may be considerable sampling and measurement noise at very low PSA levels due to sources of PSA other than prostate cancer (including possible remaining non-cancerous prostate tissue and other organs that produce small amounts of PSA), sample variation, and variation in processing and calibration of the test.  Statistically significant changes over three or more samples need to be seen to have some confidence in any conclusions.  On the flip-side, a super ultra-sensitive, gold nano-particle based PSA test with much greater sensitivity is being worked on, so there must be a lot of people who think that earliest possible detection of PSA rising may be important to improve long-term survival rates.

I can understand why most medical professionals don't want, use, or recommend ultra-sensitive PSA tests. They don't want to create anxiety in their patients over fluctuating PSA levels down in the noise region, nor deal with patients worried about insignificant rises. Plus, from their perspective, a conventional medical perspective, they don't need to know about rising PSA until the level reaches the 0.2 to 0.5 range, when they will recommend secondary treatment.

As a patient who has received a recommendation to get a PSA test every three months for five years after surgery, I have a much different perspective and needs:
  1. It's commonly said that PSA after radical prostatectomy is more important and useful than before surgery (assuming your cancer is producing PSA). The rapid near zeroing of PSA is one of the reasons we choose radical prostatectomy, so that we can see if the treatment was successful, and quickly determine if secondary treatment is needed.  Eliminating the prostate should allow us to detect cancer recurrence early, when it's small and producing very low PSA levels, and thus improve the chance of successful treatment.  With the standard PSA test, though, we get very little information when our level is undetectable.  It feels like having an idiot light on a car dashboard instead of a gauge. Some people only want an alert when action is necessary. Others really want to be aware of what's going on for early detection and prevention of problems. I want to know what's really going on with my PSA level.

  2. I want to chart my PSA -- undetectable, undetectable, undetectable does not produce a chart.

  3. I want to know what my new baseline PSA noise floor is – what range it's fluctuating in – and undetectable tells me almost nothing.

  4. I want to see on my PSA chart if my PSA rises above the noise floor and continues an upward rising trend over multiple samples that would indicate a statistically significant rise and a conclusion of likely cancer recurrence, possibly well before the absolute level reaches 0.2 to 0.3 ng/ml that is the conventional measure of biochemical recurrence.

  5. I want to get a reasonable measure of the PSA velocity (rate of change) even when it's below or near 0.1 or 0.2 ng/ml.  Having data points from when it is below 0.1 allows velocity to be calculated with greater confidence as it passes above 0.1.  A test with a sensitivity of 0.1 ng/ml provides no or little velocity information upon receiving a first result at or above 0.1.  A second and third test a month or more apart is needed to have worthwhile information for estimating PSA velocity.  The PSA velocity is important for determining aggressiveness of the cancer recurrence, and potentially the recommended course and timing of treatment.

  6. I want to be confident that I need to get secondary treatment. Non-existent or inadequate velocity information cannot provide sufficient confidence. Not knowing my noise floor also reduces confidence because my current PSA level could be just barely below detectable, and then if it pops up to detectable, it could be just noise, but I won't know it.

  7. I want to have information that will show when it may be advisable to use a shorter interval between PSA tests prior to the level reaching 0.1 ng/ml.  If PSA stays undetectable for a year or two after surgery, urologists often recommend just annual PSA testing.  A standard PSA test result could be undetectable when the real PSA level is just under the minimum detection level of 0.1.  The next year's test could provide a result of 0.2 or higher.  That could cause immediate need for treatment decisions which most men would probably be unprepared to make, especially with no PSA velocity information.  It could also cause missing out on a year or more of life-style changes, dietary changes, alternative therapies, educating oneself, attending support group meetings, and so forth, that may help suppress cancer or guide treatment.  Ultra-sensitive PSA testing is very important when using long periods between tests.

  8. I want to get a heads-up when it may be worthwhile to initiate more research regarding treatment alternatives, look for an experimental treatment study or clinical trial that I may want to get in to, and perhaps go see a prostate oncology specialist -- hopefully well ahead of needing to make a decision and start treatments.

  9. I am doing things to hopefully reduce the chance of cancer returning, such as stress reduction, exercise, diet changes, and some recommended nutritional supplements. I'm also working to be prepared if cancer does return, but there is a limit on how extreme I'm willing to go. We all have a lot of important other things to be doing in our lives. That's why we want to exterminate the cancer – right?  But if I see a statistically significant rise in my PSA, my priorities will change.  I'll be much more motivated to do research and experimentation, plus spend time and money on fighting cancer. Ultra-sensitive PSA testing will help me prepare to wage war again.

  10. If my PSA appears to be rising, I want an opportunity to try more changes to my diet, to alter my lifestyle or neutraceutical supplement program, or to try some alternative therapy to see if I can stop the rise or reduce the velocity. I would like to avoid conventional treatments with serious side effects, such as radiation therapy or systemic drug treatment.  I might be able to delay secondary treatment until some new better treatment becomes available, such as immunotherapy.  With the standard PSA test, I may not have much time to experiment, nor will it be easy to see if I'm achieving any improvement.

  11. I believe ultra-sensitive PSA testing can help me to reduce the chance that my medical insurance provider will have to pay for expensive secondary treatment such as radiation of the prostate bed that may cost tens of thousands of dollars. I have personally talked with men who have had success with dietary changes, lifestyle changes, and alternative treatments. Doctors and medical insurers should not underestimate our body's ability to heal itself when we are motivated.

  12. Although the standard of care today may be to consider secondary treatment when the PSA level reaches 0.2 to 0.3 ng/ml, we don't know that there won't be in the future a good treatment -- maybe low side-effect and systemic -- that suggests initiating treatment as soon as a statistically significant rise in PSA level is seen. Ultra-sensitive PSA testing needs to be in use for a while to detect a statistically significant rise over three or more samples. Using ultra-sensitive PSA testing allows the patient and their doctors to be prepared to take advantage of new treatment protocols.

  13. If an ultra-sensitive PSA test shows my level to be well below 0.05 ng/ml, possibly even undetectable by the ultra-sensitive test, then I will know that my probability of long-term survival is significantly better than just knowing that it's below 0.1 ng/ml.
Ultra-Sensitive PSA tests are available from a variety of medical test labs, including Quest Diagnostics (http://www.questdiagnostics.com/), LabCorp (http://www.labcorp.com), and ARUP Laboratories (http://www.aruplab.com/). It is informative to do a keyword search of the Test Menu or Test Directory on some medical test lab websites for the keyword “prostate”. There is quite a variety of tests available related to prostate and prostate cancer. The lab test description may tell you how the test is used, and thus whether it may be of interest to you, but you will likely need to do much more research to learn about the available tests.

For those with prostate cancer that does not produce a rising PSA measurement (often an aggressive form of prostate cancer), before treatment it is important if you can to find a blood or urine type lab test that does detect your type of prostate cancer. Otherwise, after treatment, how are you going to know if the cancer is returning and it's time to seek secondary treatment? There is a variety of alternative lab tests that are an attempt to provide more accurate prostate cancer detection, some of which are still in an experimental stage. They often work by detecting one or more markers that are specific to certain kinds of prostate cancer. Work with your doctors to see if you can find a test that works for you. Seek out a prostate oncology specialist if necessary.


For some men and their family, it may be good that the standard PSA test is just an idiot light on their life's dashboard.  The standard PSA test may be best for them. But I know many men like to have a gauge that can tell them it's time to do some maintenance, let up on the accelerator some, or reduce the load on their engine. Our bodies are a lot like engines.  I strongly believe in the potential usefulness of an ultra-sensitive PSA test for those men who had prostate cancer that produced rising PSA measurements, have received any treatment that has reduced their PSA level to under 0.1 ng/ml, and will actually make some changes or take some actions that may benefit them when their ultra-sensitive PSA chart indicates cancer recurrence.  An ultra-sensitive PSA test may provide sufficient information to draw quicker and more confident conclusions, thus hopefully helping us to live longer and healthier lifes.

All post prostate cancer treatment patients with PSA levels less than 0.1 ng/ml deserve the option to choose an ultra-sensitive PSA test to give them and their doctors more information. Doctors and medical insurers should support the use of ultra-sensitive PSA testing for those patients who want it and will take some actions sooner than would be possible with standard PSA testing.  This is important -- patients or doctors who use ultra-sensitive PSA testing should have a plan on what they're going to do if statistically significant rises occur prior to the conventional threshold for recurrence of cancer.  Otherwise, much of the possible benefits are not realized.

I have published my reasons for wanting ultra-sensitive PSA testing not just to help men decide if it's something they want and should ask for, but also to help convince doctors treating prostate cancer to seriously consider educating their patients about it and offering it to them when appropriate. I also hope to help convince medical insurance organizations to cover these tests. If you want to help the cause, please give your doctors and medical insurance providers the permalink to this article (http://www.ob-ron.org/2009/10/case-for-ultra-sensitive-psa-testing.html), announce it at prostate cancer support groups you attend, refer to it in prostate cancer forums in which you participate or in your blogging or micro-blogging, and message friends who might be interested. 

If you have constructive thoughts on this subject or further reasons to use ultra-sensitive PSA testing, please add a comment to this post.

Further Reading: