Undetectable Concept Revisited

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compiler
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   Posted 1/29/2011 11:52 AM (GMT -6)   
OK, we all know the technical definition. If your lab test finds PSA, then it's detectable. For example, my local has its lowest reading as <0.01 (undetectable). My first post-op reading was 0.01 so technically it was not undetectable. However, if I used the single digit PSA, then until 1/4/11, almost a year after my surgery, it would have read <0.1 (undetectable).
Now, so far it's just semantics.
 
But then you read all kinds of studies where they refer to PSA levels remaining undetectable for xxx time. Yet, they never seem to specify the test. Another example is the MSK nomograph. It has this:
 
Elevated Post-Radical Prostatectomy PSA
Did the PSA value obtained after radical prostatectomy remain elevated? (I.E. Did the PSA value never decrease to an undetectable level?)
 
Well, I think in my case, the technical answer is YES but I believe the correct answer would actually be NO since they are probably referring to the single digit PSA.
 
Comments?
 
Mel

PSA-- 3/08--2.90; 8/09--4.01; 11/09--4.19 (PSAf: 24%), PCA3 =75 .
Biopsy 11/30/09. Gleason 4+3. Stage: T1C. Current Age: 64
Surgery: Dr. Menon @Ford Hospital, 1/26/10.
Pathology Report: G 4+3. Nodes: Clear. PNI: yes. SVI: No. EPE: yes. Pos. Margin: Yes-- focal-- 1 spot .5mm. 100% continent by 3/10. ED- in progress. PSA on 3/10/10-: 0.01. PSA on 6/21/10--0.02. 9/21/10--0.06; 1/4/11-0.13 CRAP!

Purgatory
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Total Posts : 25393
   Posted 1/29/2011 12:02 PM (GMT -6)   
Despite the endless debates over sensitive vs. ultra-sensitive testing, being in the realms of tolerance for a particular test machine, the anything <.1 being a 'zero', etc. I can only re-tell what both my uro/surgeon and my radiation oncologist told me, independently of each other. A first post surgical PSA of .05 showed my uro that all the cancer was not removed, or had already relocated away from the prostate. The radiation doctor is of the same exact opinion and the same number. Unlike RT as a primary treatment, where you can get a legitimate bounce, she said that after SRT, any rise would indicate failure of the SRT. Kind of harsh, but that is what both doctors told me.
Age: 58, 56 dx, PSA: 7/07 5.8, 10/08 16.3
3rd Biopsy: 9/08 7 of 7 Positive, 40-90%, Gleason 4+3
open RP: 11/08, on catheters for 101 days
Path Rpt: Gleason 3+4, pT2c, 42g, 20% cancer, 1 pos marg
Incont & ED: None
Post Surgery PSA: 2/09 .05,5/09 .1, 6/09 .11. 8/09 .16
Post SRT PSA: 1/10 .12, 4/8 .04, 8/6 .06 11/10 Not taking it
Latest: 6 Corr Surgeries to Bladder Neck, SP Catheter since 10/1/9, SRT 39 Sess/72 gy ended 11/09, 21 Catheters, Ileal Conduit Surgery 9/23/10

Tim G
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   Posted 1/29/2011 12:19 PM (GMT -6)   
Interesting question, Mel.  I'm pretty sure that the term "undetectable", as it applies to most studies, refers to the standard <0.1 ng/mL.  You are, however, exactly right, in noting that with the newer ultrasensitive assays, any value reported, for example, 0.02, is indeed detectable.  The question remains, is a PSA value less than 0.1 meaningful?  Do you start further treatment based on this, or based on an upward trend? 
 
A lot, undoubtedly, is based on an individual case and the pathology report.  And also on the medical philosophy of the physician and patient.  Is it better to treat on the possibility of further increase in PSA, or is it better to wait and see.  This is perhaps the same kind of decision process behind how to treat an early cancer like mine.  Is it indolent?  Should I wait and see (Active Surveillance), should I treat with surgery, with radiation, or other treatment (including experimental treatments) ? 
 
One thing is certain:  prostate cancer is protean, perplexing disease. 
PSA quadrupled in one year (0.6 to 2.6)
DRE negative Retested at 3 months
1 of 12 biopsies positive (< 5%) G6
RP open surgery June 2006 at age 57
Bilateral nerve-sparing
Organ-confined to one minuscule area, downgraded to G5
Prostate weight 34 grams
PSAs < 0.1

Fairwind
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Total Posts : 3893
   Posted 1/29/2011 12:58 PM (GMT -6)   
My philosophy..When you have completed your primary treatment, you should be out enjoying what is left of your life as much as possible, not obsessing over PSA numbers..If you are having a reoccurrence, you will know about it soon enough..There is not much you can do about it, so why worry about it?? Just play the next hand...
Age 68.
PSA at age 55: 3.5, DRE normal. Advice, "Keep an eye on it".
age 58: 4.5
" 61: 5.2
" 64: 7.5, DRE "Abnormal"
" 65: 8.5, " normal", biopsy, 12 core, negative...
" 66 9.0 "normal", 2ed biopsy, negative, BPH, Proscar
" 67 4.5 DRE "normal"
" 68 7.0 third biopsy positive, 4 out of 12, G-6,7, 9
RALP Sept 3 2010, pos margin, one pos vesicle nodes neg. Post Op PSA 0.9 SRT, HT NOW

compiler
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   Posted 1/29/2011 1:04 PM (GMT -6)   
David:
 
I thought that after SRT you may very well get a rise or two because there is a delay in the destruction of the cells. Then eventually (ideally) it goes down and down and reaches a nadir. Then you first start seeing what happens thereafter.
 
Do I have it wrong? Maybe someone else can chime in here?
 
Also, my point is that in so many studies/nomographs they talk about undetectable/detectable and time until it gets detectable. Well, my time is technically 0 months, but I suspect by some of their measures it is 12 months. It makes a difference when one attempts to try and draw some conclusions, especially concerning the probability of success with some treatments. Some studies do define detectable and it never seems to be the ultreasensitive measure.
 
Mel
 
 

daveshan
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Total Posts : 363
   Posted 1/29/2011 2:07 PM (GMT -6)   
Mel,
IMO with the new technology all we can do it look at the trends and not get too caught up in the terms. My Dr and I have decided that at 0.05 we cock the gun (or rather the linear accelerator) and at a subsequent rise we fire.

With detection limits of <0.1, <0.04 (my lab) and <0.01 it sure gets confusing. As for the nomograms, it would depend on what test they were developed for/with, it's a tough call.

142
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Date Joined Jan 2010
Total Posts : 7087
   Posted 1/29/2011 3:28 PM (GMT -6)   
Mel,
 
If you consider the source, "undetectable" means the same thing for all tests - "less than the equipment/test will detect".
 
Of course it varies according to the lab, equipment, and test used.
 
My Uro/Surgeon does a standard test with Bostwick. Since surgery, it has been consistently <0.1, "undetectable".
My GP uses a different lab, and has changed labs since this all started. In his case, I have had two <0.01, "undetectable", and the last was 0.02.
 
For my GP, it is detectable.
For my Uro/Surgeon, it is undetectable.
 
Back to the Twilight Zone.
 
 

Purgatory
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Date Joined Oct 2008
Total Posts : 25393
   Posted 1/29/2011 3:56 PM (GMT -6)   
Mel, just telling you what my radiation oncologist said at the completion of my SRT, perhaps her remark was flavored differently because of my PSA velocity issues from the start. Again, she said any rise after the SRT would signify that the radiation failed.
Age: 58, 56 dx, PSA: 7/07 5.8, 10/08 16.3
3rd Biopsy: 9/08 7 of 7 Positive, 40-90%, Gleason 4+3
open RP: 11/08, on catheters for 101 days
Path Rpt: Gleason 3+4, pT2c, 42g, 20% cancer, 1 pos marg
Incont & ED: None
Post Surgery PSA: 2/09 .05,5/09 .1, 6/09 .11. 8/09 .16
Post SRT PSA: 1/10 .12, 4/8 .04, 8/6 .06 11/10 Not taking it
Latest: 6 Corr Surgeries to Bladder Neck, SP Catheter since 10/1/9, SRT 39 Sess/72 gy ended 11/09, 21 Catheters, Ileal Conduit Surgery 9/23/10

Jerry L.
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   Posted 1/29/2011 7:57 PM (GMT -6)   
Kind of off topic, but what exactly is "undetectable" aside from the numbers? Is it that it lies dormant and something triggers it to start growing? Or, is it that it is so small and grows relatively slow and technology can't detect it?
Nov. 2009 Dx at Age 44
Dec. 2009 DaVinci Robotic Surgery
Jan. 2010 T3b, Gleason 9
Feb. 2010 Adjuvant Radiation

PSA History:
-----------------
Nov. 2009 4.30
Feb. 2010 <.05
May 2010 <.05
Aug. 2010 <.05
Nov. 2010 <.05

142
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   Posted 1/29/2011 8:01 PM (GMT -6)   
Jerry,
 
Back to the source -
"undetectable" means the same thing for all tests - "less than the equipment/test will detect"
 
The problem is what test you use.

An38
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Date Joined Mar 2010
Total Posts : 1152
   Posted 1/30/2011 6:44 AM (GMT -6)   
My husband's results are detectable (0.03 or 0.01) depending on which assay is used (we do the both tests assays at the same time).

However the trigger for action is 0.05 according to our urologist and given the good news on the pathology and pre-surgery psa (organ confined, negative margins, negative extraprostatic extension, negative seminal vesicles, 3+4) it seems from our research that no one will actually do anything till it reaches 0.05 anyway.

So undetectable on the ultrasensitive may not actually result in any action - in the case of a favourable pathology report all you get from a low detectable reading is knowledge - but in my opinion this knowledge us worth having.

An
Husband's age: 52. Sydney Australia.
Family history: Mat. grandfather died of PC at 72. Mat. uncle died of PC at 60. He has hereditary PC.
PSA: Aug07 - 2.5|Feb08 - 1.7|Oct09 - 3.67 (free PSA 27%)|Feb10 - 4.03 (free PSA 31%) |Jun10 - 2.69. DRE normal.
Biopsy 28Apr10: negative for a diagnosis of PC however 3 focal ASAPs “atypical, suspicious but not diagnostic” for PC. Review of biopsy by experienced pathologist, 1/12 core: 10% 3+3 (left transitional), 1/12 core: ASAP (left apex)
Nerve sparing RP, 20Aug10 with Dr Stricker. Post-op path: 3+4 (ISUP 2005). Neg (margins, seminal vesicles, extraprostatic extension). Multifocal, with main involvement in the fibro-muscular zone. T2C.
Post RP PSA,
Lab 1: Sep10 – 0.02|Nov10 – 0.03|Dec10 – 0.03
Lab 2: Nov 10 - 0.01|Dec10 – 0.01

Ed C. (Old67)
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   Posted 1/30/2011 11:49 AM (GMT -6)   
Mel,
The ultra sensitive test is supposed to detect PSA as low as .001 although slight vriations on that numberare concidered undetectable. My first 5 PSA tests ranged from .004 to .005 until my last one (diffrent lab) came back <.008. I tried to call the lab to find out why it had a less than sign infront or whether it was .008. It seems odd to have the less than sign when it can go lower than that.

compiler
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Date Joined Nov 2009
Total Posts : 7270
   Posted 1/30/2011 12:21 PM (GMT -6)   
Just to reiterate my point:
 
My question is not the definition of undetectable. We know what that means and it depends on the sensitivity of the test.
 
My problem is reading assorted articles when they talk about undetectable. Often they just do not define that in the article.
 
eg: Suppose an article said "based on our research we recommend further treatment as soon as the PSA becomes detectable"?
 
If their research involved the one-digit test, that would be a 0.1 threshhold. But maybe they are using a more sensitive test.
I wish all of these articles would be more specific!
 
Mel

Purgatory
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Date Joined Oct 2008
Total Posts : 25393
   Posted 1/30/2011 12:23 PM (GMT -6)   
Ed, not picking on you in particular, but you post begs me to say this. What is the point of having a PSA test read accurately to .xxx. Doctors and patients already have anixety problems with tests reading down to .xx. Look at what you saying with your numbers, you have <.008, which means you have less than even an ultra low .01, and so far under the threshold of having your PSA <.1.

I could be wrong, but these ultra ultra tests are indeed causing a lot of needless worry. Just don't see the point of a reading that accurate if it serves no useful purpose other than scaring the patient into thinking there is some problem or trend, when there really isn't.

I couldn't imagine in my journey having a PSA reading of under .01, like yours, I would be dancing in the streets and letting off sky rockets to celebrate.

My problem isnt with you, of course, its the silliness of a test that can register that low.

David in SC
Age: 58, 56 dx, PSA: 7/07 5.8, 10/08 16.3
3rd Biopsy: 9/08 7 of 7 Positive, 40-90%, Gleason 4+3
open RP: 11/08, on catheters for 101 days
Path Rpt: Gleason 3+4, pT2c, 42g, 20% cancer, 1 pos marg
Incont & ED: None
Post Surgery PSA: 2/09 .05,5/09 .1, 6/09 .11. 8/09 .16
Post SRT PSA: 1/10 .12, 4/8 .04, 8/6 .06 11/10 Not taking it
Latest: 6 Corr Surgeries to Bladder Neck, SP Catheter since 10/1/9, SRT 39 Sess/72 gy ended 11/09, 21 Catheters, Ileal Conduit Surgery 9/23/10

142
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Date Joined Jan 2010
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   Posted 1/30/2011 1:03 PM (GMT -6)   
Mel,
 
If those who publish the studies don't say what their definition of undetectable is, I would expect that you, the questioning type, will email or write and ask them.
 
I tend to use the definition the uro gives me, as to use something else, and present him with something contradictory to his advice based on numbers at 2 or 3 decimal places, simply sets me up to have to go find another uro. I know some would argue that I need to be more aggressive, but to what end?
 
 

clocknut
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   Posted 1/30/2011 1:33 PM (GMT -6)   
We have a smoke detector in our house that's so overly sensitive that it goes off whenever we fry bacon. Is that a good thing or a bad thing? It might actually be a better smoke detector if the threshold were set higher so that it would only sound when there's a real fire. Or maybe it's good that even a few smoke particles cause it to scream in protest. I'm not sure.

Our neighbors had a dog that would bark at everyone passing by the house. Now, a dog that barks when danger presents itself is a good thing, but a dog that barks indiscriminately is definitely not good.

I'm thinking the ultra-sensitive tests may be like that smoke detector and that dog. If they just get folks spun up unnecessarily, what good are they?

I only need my household thermometer graduated in degrees, not in hundredths of a degree. If on a cold winter's day it were to climb from .01 to .02 degrees, has the temperature really doubled? Does it have any significance? And for me that's the question with the ultra-sensitive test. Do these minute changes signify a change that has any clinical significance? Or is the jury still out on that?
Age 65
Dx in June 2010.
PSA gradually rising for 3 years to 6.2
Biopsy confirmed cancer in 6 of 12 cores, all on left side
Gleason 7 (3 + 4)
Bone scan, CT scan, rib x-rays negative.
DaVinci 8/20/10
Negative margins; negative seminal vesicles
5 brothers, ages 52-67 ; I'm the only one with PCa
Continence OK after 7 weeks. ED continues.
PSA 1/3/10: 0.01

compiler
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Date Joined Nov 2009
Total Posts : 7270
   Posted 1/30/2011 2:50 PM (GMT -6)   
Clocknut:
 
My opinion is:
 
I see little use for the 3-decimal accuracy. Going from 0.001 to 0.004 means nothing.
 
The 2 decimal accuracy is useful.
 
In my case, it has served as an early warning system where most likely I'll be starting SRT earlier, but in the face of a clear BCR. It also allowed me to see the radiation guy and get everything in place.
 
But I have paid a penalty in worry and anxiety. But I would still be anxious before every PSA test.
 
My doctors at Ford and at Umich all prefer the single decimal test.
 
Mel

Jerry L.
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   Posted 1/30/2011 2:51 PM (GMT -6)   
I recently cooked salmon that made the smoke detector go off. We've also purchased a dog that barks too much. And frankly, I don't know what the temperature is, but I'm cold in PA.
Nov. 2009 Dx at Age 44
Dec. 2009 DaVinci Robotic Surgery
Jan. 2010 T3b, Gleason 9
Feb. 2010 Adjuvant Radiation

PSA History:
-----------------
Nov. 2009 4.30
Feb. 2010 <.05
May 2010 <.05
Aug. 2010 <.05
Nov. 2010 <.05

clocknut
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   Posted 1/30/2011 3:30 PM (GMT -6)   

Mel, I'll continue to hope that what looks like an upward trend in your numbers turns out to be some sort of temporary aberration.  I'm sure I'd probably be feeling the same kind of anxiety if I were in your shoes.  The disease is bad enough without the worry and anxiety.  Hang in there.


BillyMac
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   Posted 1/30/2011 4:09 PM (GMT -6)   
Ed C. said...
Mel,
The ultra sensitive test is supposed to detect PSA as low as .001 although slight vriations on that numberare concidered undetectable. My first 5 PSA tests ranged from .004 to .005 until my last one (diffrent lab) came back <.008. I tried to call the lab to find out why it had a less than sign infront or whether it was .008. It seems odd to have the less than sign when it can go lower than that.


Ed,
I may be wrong but I don't think that any assay can detect down to 0.001. I believe the most sensitive test available uses the DPC Immulite 2000 and has a lower detection limit of 0.003. As for your reports of .004, .005 and then <.008, it would be interesting to see the labs reason for the change in reporting the result ------- they have all been <.008
Bill

Post Edited (BillyMac) : 1/30/2011 2:12:05 PM (GMT-7)


Ed C. (Old67)
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   Posted 1/31/2011 8:03 AM (GMT -6)   
David and BillyMac,
The lab that reported <.008 is the one used by my GP doctor. All my other tests have been by the lab that my Uro. uses. I agree with David that sometimes the ultra senstive test can give us unnecessary anxiety. BillyMac, regardless to what the lowest number the ultra sensitive test can detect,why would the reported result show <.008 when it detect below that number? Is it a typo in the report?
Age: 67 at Dx on 12/30/08 PSA 3.8
2 cores out of 12 were positive Gleason (4+4)
Davinci surgery 2/9/09 Gleason 4+4 EPE,
Margins clear, nerve bundles removed
Prostate weighed 57 grams 10-20% involved
all PSA tests since (2, 5, 8, 11, 15, 18 months) undetectable
Latest PSA test (21 months) .005

142
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Date Joined Jan 2010
Total Posts : 7087
   Posted 1/31/2011 8:54 AM (GMT -6)   
Ed,
 
There are probably two different tests (perhaps the same equipment, perhaps different).
 
I asked for details at my GP's new lab - they have multiple locations, and different equipment at each. Tests get distributed by load, so there is no guarantee that the same equipment is used two times in a row. They do report the machine used.
 
So it is entirely possible to get a <.01 one time, and a <.03 another.
 
Doesn't help much, does it?

LV-TX
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Total Posts : 966
   Posted 1/31/2011 8:56 AM (GMT -6)   
Mel,

The oncologist that I spoke with said what you are thinking. Anything above the detection limits is detectable, regardless of what test you are using. But he said it is only really useful after the results are above the 0.2 threshold.

Best of luck to you
You are beating back cancer, so hold your head up with dignity

Les

Robotic Surgery Sept 2008
PSA increasing since January 2009
Current PSA .44 (29 months)
PSA Doubling time approx. 6 months

Putt
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Date Joined Aug 2010
Total Posts : 154
   Posted 1/31/2011 12:11 PM (GMT -6)   
Keep in mind that other organs produce androgen's, that can affect the levels found with the ultra test. That is one of the reasons that Dr. Stephen B. Strum considers <0.05 as non-detectable. So my question is why would anyone be concerned about levels below 0.050?

This quote can be found on this site. http://en.wikipedia.org/wiki/Androgen

"• Dihydrotestosterone (DHT): a metabolite of testosterone, and a more potent androgen than testosterone in that it binds more strongly to androgen receptors. It is produced in the adrenal cortex.
PSA at Dx 105 at age 68, 4/04. ADT (Lupron only), RRP, 5/04. Gleason 4+5=9, Staged pT3bc NO MO, 3D rad, 40 treatments, 8/04. PSA 1/05 <0.01. ADT till 7/07. PSA 0.03 12/08, 0.07 4/09, 0.13 8/09, 0.19 12/09, 0.30 4/10, 8/10 0.42, 12/10 47. Will start ADT3 after PSA reaches 1.2.

Zen9
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Date Joined Oct 2009
Total Posts : 314
   Posted 1/31/2011 12:50 PM (GMT -6)   

For what it's worth, my PSA readings taken at M. D. Anderson are not the ultrasensitive type but merely report "<0.1 = undetectable."

Prompted by an earlier discussion of this issue, I asked about ultrasensitive tests and was told that it was not uncommon to register very low levels of PSA after surgery but that anything under 0.1 ng/ml was "not clinically significant."  

I do not know - because I did not ask - whether they would switch to ultrasensitive tests once you passed 0.1 ng/ml.

Mel, I strongly suspect that "undetectable" for purposes of, e.g., the MSK nomographs is <0.1, but as someone already advised you, you could always email to find out.

Zen9

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