Labcorp has indeed changed its uPSA undetectable back to <0.006 ng/mL

NorCal posted yesterday that after several recent undetectable Labcorp results of <0.014, he got a test back with the "old," lower undetectable of <0.006.

I wrote yesterday to the person at Labcorp who, this past November, had answered my previous uPSA question (why they changed from <0.006 to <0.014), asking if they had changed yet again. I ended my email with the question:

"Has Labcorp changed its uPSA undetectable back to the limit of blank, <0.006 ng/mL? (Since my last test, on 4/12/21, was 0.018, I can’t tell.)"

and got this reply today:

"Yes, that is the case. We were able to make this change because our method manufacturer changed their FDA approved instructions for use to allow it."

(The manufacturer of the assay is ROCHE.) For any of you interested in the technicalities (which are IMO fascinating) this has to do with whether users (e.g. Labcorp) of the assay must use the limit of blank of the assay (<0.006 ng/mL) or the limit of quantitation (<0.014 ng/mL) for undetectable results for this specific assay.

When you run some assays (e.g. this type of PSA test) on a blank sample (with no PSA in this case), you don't get the zero you might expect, but rather values that ranges between zero and the "limit of blank" (LoB) (0.005 in this case). The LoB overlaps with the limit of detection (LoD), which, in turn, overlaps with the limit of quantitation (LoQ). There is an explanatory figure in this excellent paper:

Limit of Blank, Limit of Detection and Limit of Quantitation (2008)

I do think you have to take extremely low results with a nanograin of salt as far as their accuracy goes (in other words precision at the low end may not equate to accuracy). What is of crucial interest to us all is whether our PSA is stable or increasing.

However, Labcorp's latest change is helpful for those wanting to know their post-RP PSA nadir, since a nadir <0.010 predicts a smaller statistical chance of encountering BCR than one >0.010. The <0.014 lower limit was a tad too high for this distinction.

As the supermarket tabloid says, Enquiring minds want to know.

We now return you to your regularly scheduled posts.

Djin

Hey Mumbo. I've actually thought about the exact meaning of a reported <0.10. My interpretation is:

0.12, 0.11, 0.10 can be detected, 0.10 being the smallest. So anything lower is reported as <0.10.

If you report <0.1, I would infer that the lowest detectable is 0.1, followed by 0.2, 0.3... and not 0.2, 0.21, 0.22 or 0.11, 0.12

By "can not resolve 0.10 from 0.09." do you mean can detect 0.10 but not 0.09? If so, I think that is the case if your limit of detection is truly 0.10.

Quest's limit is 0.2, so their undetectable would be <0.2. I assume after 0.2 comes 0.3. We can't assume the right-most digit goes down to 0, although it may. I don't think their first detectable values are 0.20, 0.21, or their undetectable would be <0.20.

But I could be wrong (this actually happened in 1964), and anyone can have a dog in the fight. Let's hear from the analytical chemists out there.

You could try writing to Abbott and asking.

Post Edited (DjinTonic) : 7/21/2021 11:28:15 AM (GMT-6)

mattam said...
...Does a sensitive test ever report, for example, 9.37 or 56.61?

Yes, see this Labcorp sample result of 2.001. (Patient Name: Stanley Kubrick)

I believe all results for their uPSA test have 3 decimal places.

Djin

Post Edited (DjinTonic) : 7/21/2021 11:51:30 AM (GMT-6)

Ok, I'll put on my chemist hat.... (or coat, if you prefer):

Generally, when reporting results for ANY analytical result there are a few basic rules:

Rule 1: You report EXACTLY the number of defined signifcant figures for the test in question. This information is found in the detailed instructions for the method being used. So, it appears that the Abbot test defines and requires the use of ONE significant figure. Hence, the use of 0.1, not 0.10.

Rule 2: For all methods, there is a low limit of detection, as well as the limit of blank and the limit of quantitation. (that is a really good article that doesn't go TOO far into the weeds.) The reported value is going to be reported in comparison to the limit of detection--which is a statistically defined term, and if you instrument comes up with a value below that limit, it is NEVER reported, only the "<".

Rule 3: Technically, all reports should ALSO include the limit of precision, which is a +/- value, also defined statistically--usually +/- 1 standard deviation from a mean value where the same sample is run by a LOT of technicians on numerous instruments--and the bell curve of results give you that value. All it really says is that HERE is your value, and based on 10,000 other tests, your value is 99% certain to be between that number and a little higher or lower.

By the way, one should also remember that zero is not, strictly speaking, a number. A series of values can approach zero...but you'll never be able to measure a true zero.

Well, maybe the technician sometimes reports it as <0.10, but if he's in a hurry he reports it as <0.1. 😉

Ya'll,
Interesting discussion to me ,who really has no interest. Also certainly I am not a chemist(flunked that class)
Quest in California actually reported mine recently as <0.1 ,which had no real meaning for me as My Cancer Center uses their own lab and reports their ultra sensitive tests as , <0.014. So I just see mine as "undetectable" and also as a laugh, nearly less than zero(lol)
Winging it in So Cal
PS It's 105 degrees hot ya'll, that's 105.0 is much less than 105.01...or is it?
PSS Dijin Tonic-in your last example, doesn't 0.0001223 have & 7 significant numbers? also if a PSA was THAT low, as you know, all those numbers are actually insignificant (lol) I need a Gin and Tonic after this post!

Post Edited (Wings of Eagles) : 7/21/2021 5:23:09 PM (GMT-6)

Ah for the days of slide rules and analog measurement systems, where the most you could have was 3 significant figures---which was good enough to get us to the moon and back.

halbert said...
Ah for the days of slide rules and analog measurement systems, where the most you could have was 3 significant figures---which was good enough to get us to the moon and back.

But was it really enough? Hidden Figures poignantly depicted the role of women and long-hand calculations (with the aid of mechanical calculators and early computers) even earlier for Glenn's orbiting. I doubt 3 significant figures are enough to get you into an accurate orbit let alone to the moon.

Adding this that I just found:


"Originally Answered: How many digits of pi was the engineers apply to land Neil Armstrong on the moon ?
I don't know how many significant digits were used in the calculations, but you wouldn't have needed very many.

Here is a table of errors if you were to calculate the average circumference of the Moon's orbit from the average diameter of the orbit (384,467 km) using the following number of decimal points of pi (assuming the orbit was circular):

5 digits: 3.14159 Error: 1 km
8 digits: 3.14159265 Error: 5 inches
11 digits: 3.14159265359 Error: 3/1000 inch

Not many digits are needed to get more than enough accuracy. 5 would have been enough for orbit insertion around the moon. Any of the above calculations could have been easily done in the 1960s using log tables.

(The IBM 1620 mainframe computer, available in 1961, could do arithmetic using an arbitrary number of digits of precision, so would have been able to do the orbital calculations to any accuracy desired.)"

Djin

Post Edited (DjinTonic) : 7/21/2021 8:23:13 PM (GMT-6)

Makes me wonder when Labcorp changed back to <0.006? Labcorp drew blood on 7/9 and my result was <0.014. Or perhaps they're rolling out the change date specific region by region.

Maybe it's good that the PSA test wasn't available during the Moon-Shot era.

This was "way back" in 2014:

Ultra-sensitive protein detection via Single Molecule Arrays towards early stage cancer monitoring

"Abstract
The early diagnosis of cancers and continued monitoring of tumor growth would be greatly facilitated by the development of a blood-based, non-invasive, screening technique for early cancer detection. Current technologies for cancer screening and detection typically rely on imaging techniques or blood tests that are not accurate or sensitive enough to definitively diagnose cancer at its earliest stages or predict biologic outcomes. By utilizing Single Molecule Arrays (SiMoA), an ultra-sensitive enzyme-linked immunosorbent assay (ELISA) technique, we were able to measure increasing levels of prostate specific antigen (PSA) within murine serum over time, which we attribute to tumor development. The measured concentrations of PSA were well below the detectable limits of both a leading clinical diagnostic PSA ELISA assay as well as a commercial ultra-sensitive PSA assay. Our work benchmarks the role of SiMoA as a vital tool in monitoring previously non-detectable protein biomarkers in serum for early cancer detection and offers significant potential as a non-invasive platform for the monitoring of early stage cancer."

From the Full Text:

"The limit of detection (LOD) of a leading clinical diagnostic PSA ELISA assay (Siemens, usa.healthcare.siemens.com) is 100 pg/mL and the LOD of commercially available ultra-sensitive ELISA-based PSA tests is between 3–10 pg/mL11. The experiments described in this paper are compared to these two benchmarks. We obtained a LOD of 0.005 pg/mL for PSA using SiMoA, which is significantly more sensitive than ELISA and is comparable to previous SiMoA work9. Other literature reports have also demonstrated sensitive PSA tests, including recent work by Liu et al. where they utilized gold nanoparticles to create a colorimetric ultra-sensitive assay for PSA with a LOD of 0.0031 pg/mL"

[Emphasis mine]

0.0031 pg/mL = 0.0000031 ng/mL

Me: My PSA report just came back <0.0000031 ng/mL --- should I be worried?
Mork: "Na-No, Na-No"

Halbert, an EPA site has "A way to visualize one part per billion (ppb) in water is to think of it as one drop in one billion drops of water or about one drop of water in a swimming pool. One part per million is about 1 cup of water in a swimming pool"

Googling, I see: 1 drop water ≈ 1.5 x 10²¹ molecules, 1 grain salt ≈ 3.09 x 10¹⁸ molecules

Don't we have to make the swimming pool "much" saltier?

Djin

Post Edited (DjinTonic) : 7/22/2021 7:48:57 AM (GMT-6)

Djin,

My entire professional life has revolved around the arcane world of ultrapure water, and we certainly DO care about 1 ppb of contaminants in water in specific situations. A typical specification for ultrapure water treatment is "< 5 ppb (ug/L) total dissolved solids". 5 ppb of sodium in pharma-grade water makes it unusable. You're right, you'd need a lot more than 1 ppb in your swimming pool to notice it. 1% is 10,000 ppm/10,000,000 ppb.

For comparison, most people can smell ammonia or chlorine at 5 ppm. If you were to drink ultrapure water in survival level quantities, you would eventually die of mineral depletion--your body would remove calcium from your bones to keep your electrolyte levels up.

GG, that's a good number, but technically you can't say that it's below the previous <0.014.