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Undetectable PSA: What does it mean?

PSA is undetectable when it is too low to be detected by the assay system being used.

The Prostate Cancer Research Institute (PCRI) defines it as "a PSA of <0.05 using a hypersensitive assay such as DPC Immulite 3rd generation PSA or Tosoh assay."

Johns Hopkins defines it as less than 0.2 ng/ml.
http://urology.jhu.edu/highlights/seeds.html

Walsh says that with levels as high as 1.0 to 1.5 ng/ml, this means that 10-15 grams or more of viable prostate are present (the PSA level in the serum is approximately 10% of the weight of the prostate).
http://urology.jhu.edu/highlights/seeds.html

Hybritech
http://www.beckman.com/products/testdetail/access/psa.asp

Immulite
http://www.dpcweb.com/products/immulite/immulite.html

Tosoh
http://www.tosohmedics.com/Docs/product.html

Subject: Re: [PP] What is undetectable PSA?
To: PROSTATE@LISTSERV.ACOR.ORG

Winnie wrote:
> Date: Wed, 6 Mar 2002 17:57:14 -0500
> From: Don and Winnie Janzen
> Subject: What is undetectable PSA?

> > Could someone one please tell me what is considered "undetectable PSA = > reading". My husband Don had a RP last June and had two checkups since = > where his PSA was "undetectable". He just had another PSA reading done = > at another hospital and it came back as 0.1. We want to know if that is = > considered "undetectable"??? Or, could the reading be different at a = > diff. hospital?
> We are worried.

> > Thanks.
> Winnie

Winnie,

As I see it, "undetectable" as related to PSA is used to convey two somewhat different meanings.

>From a strict technical point of view, an "undetectable" reading is one where the equipment failed to detect the marker sought, PSA in this case. These "undetectable" readings are usually reported as "less than X ng/ml", where X is the "detection limit" of the lab, assay, or machine used. As I recall, X = 0.2 ng/ml for Hybritech (one of the original assays, still in use), 0.03 ng/ml for Tosoh (one of the first high sensitivity assays), and 0.002 ng/ml for the DPC IMMULITE 2000 (one of the ultrasensitive "third generation" assays). Therefore, for example, a true PSA level of 0.1 ng/ml would be reported as "undetectable" (less than 0.2 ng/ml) by a lab using the Hybritech but would be reported as "detectable" by a lab using the Tosoh or the DPC 2000. As you know, to properly assess the PSA trend all readings should be obtained from the same lab using the same assay or machine type.

A different perspective arises when "undetectable PSA" is loosely used to describe the expected outcome from a definitive local procedure (i.e. one which is expected to totally eradicate the tumor by completely removing or destroying it). For example, "a successful RP should result in an undetectable PSA". Here, there are other factors that must be taken into account. First, even if the surgery removed the entire gland and there was no prostate cancer elsewhere (i.e. there had been no spread of the cancer beyond the prostate prior to the surgery), there could still be minute amounts of circulating PSA produced by other tissues which would be detectable by the ultrasensitive assays. This is why, according to Dr. Stamey from Stanford (one of the preeminent prostate cancer surgeons) when using an ultrasensitive PSA assay (such as the DPC 2000) one need not start to worry about a possible "recurrence" unless the PSA is detected above 0.05 ng/ml (notice that the Hybritech assay would still report this as "undetectable", or <0.2 ng/ml).

In addition, as I understand it, the PSA could be higher than 0.05 ng/ml and still not represent a "recurrence". For example, it appears that it is not uncommon for the surgeon to inadvertently cut through the edges of the gland as it is removed (i.e. some of the gland might have been left behind). When the tumor extends to that area the result are "positive margins" and a higher probability of recurrence. But when the portion of the prostate left behind is benign, the PSA might well be above 0.05 ng/ml because the prostate tissue left behind might continue to produce PSA and/or even regenerate, even though there is no tumor left. As I see it, the key difference is that if tumor was left behind the PSA will not only be "detectable" but it will continue to increase in a roughly exponential fashion (unless the residual tumor withers by itself due to the lack of blood supply or via the activities of the immune system), whereas if only benign tissue is left behind the PSA will be detectable but will either remain mostly stable or, at most, will increase slowly in a more linear fashion.

When the definitive treatment is radiation a different situation exists. As I understand it, therapeutic radiation relies in the expectation that, although both the cancerous and the benign cells might sustain an equivalent amount of damage to their DNA, the cancerous cells will be more unlikely to be able to repair themselves (because of their already defective DNA) and, thus, the radiation will tend to selectively kill more cancerous cells than benign cells. The aim of therapeutic RT is to apply a dose that will kill all of the cancerous cells but not necessarily all of the benign cells. This, IMO, explains why a "successful" RT might result in a stable PSA well above the PSA level expected from a "successful" RP. It also means, IMO, that it is not proper to compare the "success rates" between RP and RT by merely comparing their PSA outcomes if these outcomes are rigidly expressed as whether they are above or below any given threshold. As I say, as long as the PSA remains stable there is reason to hope that cancer is not present. Of course, given how long it takes some times for a residual tumor to manifest itself as a rising PSA, one can't be sure until many years have passed.

I am sure there is more to it than what I posted above but I hope this might help someone. Any constructive comments are welcome.

Tony Eiranova

I am not a medical doctor. The foregoing is not medical advice. It is only my opinion. You should seek other opinions from qualified licensed medical professionals.

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The material included here is intended for educational purposes only, and must not be considered a substitute for informed medical advice from your own physician.



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This information is provided for educational purposes only and does not replace or amend professional medical advice. Unless otherwise stated and credited, the content of Phoenix5 (P5) is by and the opinion of and copyright © 2000 Robert Vaughn Young. All Rights Reserved. P5 is at <http://www.phoenix5.org>. P5's policy regarding privacy and right to reprint are at <www.phoenix5.org/infopolicy>.