Anyone “below detection" with an ultra sensitive PSA test?

Posted by melvinw @melvinw, 1 day ago

Following radiation therapy for a local recurrence, I am now doing quarterly ultra sensitive PSA tests through Labcorp. My understanding is that the lower limit of detection for these ultra sensitive tests is around 0.01 (can be higher or lower depending on the assay method)

But for anyone doing ultra sensitive PSA tests, have you got a result that was below detection, whatever that exact lower limit is?

I had a RARP in 2025, and for the ten years before my recurrence, I only did regular PSA tests with the lower limit of detection of 0.1. I was always below detection until June 2025 when I tested at 0.11.

Anyway, I’m just wondering how low PSA can go, especially in guys who have had a prostatectomy. Theoretically, without a prostate and no residual cancer, PSA should be zilch/nada/zero. But I don’t have a recollection of anyone reporting PSA as undetectable on an ultra sensitive test. Can anyone say otherwise?

As a secondary question, if PSA never reaches “absolute zero” following a prostatectomy, does that imply that there are some cancer cells lingering? What is producing PSA, even at levels of say, 0.001-0.008, in a guy without a prostate?

Interested in more discussions like this? Go to the Prostate Cancer Support Group.

The nerve-wracking part for me will be if I stop ADT and stay on just Apalutamide. My onco and I are waiting for the phase 3 LIBERTAS trial to finish and publish (initial findings are due this fall; final in 2027), because it covers *exactly* my situation: for a stable, exceptional responder to ADT+Apalutamide, what happens when you stop the ADT part?

If we decide to stop ADT, it will be tempting to ask for a uPSA test every month at first for reassurance, but I know that after 4.5 years on ADT, my testosterone will be very slow coming back, and likely will come back at a lower level than it was before (if at all), so overtesting wouldn't accomplish anything. It would be a year or two before I saw if stopping ADT had any effect on my PSA.
https://ascopubs.org/doi/10.1200/JCO.2024.42.4_suppl.TPS236

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I'll address your last question/statement which was: "As a secondary question, if PSA never reaches “absolute zero” following a prostatectomy, does that imply that there are some cancer cells lingering? What is producing PSA, even at levels of say, 0.001-0.008, in a guy without a prostate?"
My response: I was the Director of Clinical and Anatomical Lab services in different hospital in my career. When a new test method and instrument are being "validated" for use, different protocols are performed to determine the test's sensitivity and specificity. Sensitivity is measuring how low (in this case) the chemical reagents and the instrument can detect and accurately quantitate the analyte (thing being measured). Specificity and sensitivity deal with false positives, false negatives, true positive, and true negatives in measuring the analyte. In other words, can interfering substances create a false positive, false negative, etc. Put another, at times confusing ,way: Sensitivity tests how well the test method identifies the "presence" of the disease state avoiding false negatives. Specificity determines how well the test method determines the "lack" of the disease state or condition being tested avoiding false positives.
One test validation method that is performed is the "Lower Limit of Detection" (or "Lower Limit of Quantitation") - "how low" can this chemical reagent and instrument that measure/detect it and offer a quantified result? I myself have had two ultra-sensitive PSA's performed by LabCorp, and their Lower Limit of Detection is that 0.006 ng/ml that we see on our test report as < 0.006 ng/ml. That tells us that the method and instrument can't accurately detect and/or quantify any value "lower than" the 0.006 ng/ml value, but it can accurately quantify it down "to" 0.006 ng/ml. This is 100% acceptable in laboratory and clinical practice. It is rather amazing to me that an assay ("test") method can accurately detect that small of a quantity of anything, but it does...so amazing. The lab...any lab...can't report anything lower than that, so they give you the < 0.006 ng/ml which would verbally read as "less than 0.006 nanograms per milliliter." So...Every quantifiable test performed in a lab has a Lower Limit of Detection or Quantification.
BTW - "Detection" and "Quantification" are different. You'll see the use of "Detection" more often when the test yields a non-numerical (qualitative) "Positive" or "Negative" test result (like a pregnancy test), not a numerical result like a glucose or PSA. And of course, the use of "Quantification" is used when the test method yields a numerical test value. There are some fine details in use of each but that is generally how it goes.
Labs also test for "accuracy" and "precision". Accuracy is the ability of the test method to quantitate the "true value" of the sample without a numerical bias upward or downward. "Precision" is basically "reproducibility", which determines whether the test method can reproduce the same numerical value over and over again. Think of a bullseye target. "Accuracy" is the ability to hit the bullseye...the true value. "Precision" is the ability for all test values to keep hitting that bullseye. It can vary though: You can have a method that shows scattered results all over the target, randomly from the outer rings to the bullseye. That test is neither accurate nor precise. You can also have a method that consistently hits the outer ring in the exact same place, away from the bullseye. That test is not "accurate", but it is "precise" (reproducible). But you would not use that method because it is not accurate. In other words, it can keep hitting the same spot in the target, but it is the "wrong" part of the target. This is where instrument calibration comes into play to adjust for that bias, but I will spare you that discussion here. So again, labs seek to validate methods that are both accurate (true) and precise (reproducible). The lab also tests the linearity of the method which tests any potential drift or bias at higher concentrations of what is being tested. Example: a diabetic patient's glucose value. The normal range for a glucose is ~70 - 100mg. All test methods are very linear in that range, but they may start to drift - skew - away from that as the glucose value starts to increase. The patient may be in crisis with a 600, 800, or higher glucose. The test method is created to determine test values from a low blood sugar down in the 30's perhaps and up to maybe 200 or 300. But when the patient's serum has such a high concentration, the test method may start to skew out in that range. The instrument or the Lab Tech will have to perform a dilution of the sample in order to bring down the value for the instrument to accurately read. The Lab Tech or instrument then calculates what the true value is so it can be reported. So, if the 600 glucose is diluted 50%, then the result reported in the instrument will be 300. Either the instrument, but usually the tech, will manually override the result in the Lab computer system, to report the true value of 600. How this is done varies from instrument to instrument and lab to lab.
Some methods are excellent, but the instrument itself can "drift" throughout the day due to it heating up, or the ambient room temperature or humidity getting too high or low, which affects the performance of the instrument measuring what is being tested. You would not believe what labs do on a daily basis and throughout the day using "Chemical Standards", "Quality Control" material that mimics real patient serum or plasma, and precision checks in order to monitor the performance of the instruments, chemical reagents, and overall validity of the tests. It was very interesting work. So...
Don't be worried that there are cells producing PSA still inside you. A whole other discussion would be about whether your surgical pathology report mentions extraprostatic extension (EPE) or surgical margins. Surgical margins means that it is very likely that some cancerous tissue did remain in your body, but...your ultra sensitive PSA value of < 0.006 ng/ml means that "if" those remaining cells are present, they are not producing any detectable PSA.

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During the time that I was on Eligard (during my 28 sessions of proton radiation), my PSA was measured at < 0.008 on one occasion.

There are other organs that produce minute levels of PSA. This fact is what makes PSA such a useful tool to detect biochemical recurrence.

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