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The ultra sensitive PSA test debate. Johns Hopkins opinion.

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Posted 10/14/2010 11:35 AM (GMT 0)
Below is Johns Hopkins opinion about the test.

"PSA Anxiety:
The Downside of Ultra- Sensitive Tests
You've had the radical prostatectomy, but deep down, you're terrified that it didn't work. So here you are, a grown man, living in fear of a simple blood test, scared to death that the PSA- an enzyme made only by prostate cells, but all of your prostate cells are supposed to be gone -- will come back. Six months ago, the number was 0.01. This time, it was 0.02.
You have PSA anxiety. You are not alone.
This is the bane of the hypersensitive PSA test: Sometimes, there is such a thing as too much information. Daniel W Chan, Ph.D., is professor of pathology, oncology, urology and radiology, and Director of Clinical Chemistry at Hopkins. He is also an internationally recognized authority on biochemical tumor markers such as PSA, and on immunoassay tests such as the PSA test. This is some of what he has to say on the subject of PSA anxiety:
The only thing that really matters, he says, is: ''At what PSA levels does the concentration indicate that the patient has had a recurrence of cancer?'' For Chan, and the scientists and physicians at Hopkins, the number to take seriously is 0.2 nanograms/milliliter. ''That's something we call biochemical recurrence. But even this doesn't mean that a man has symptoms yet. People need to understand that it might take months or even years before there is any clinical physical evidence.''
On a technical level, in the laboratory, Chan trusts the sensitivity of assays down to 0. 1, or slightly less than that. ''You cannot reliably detect such a small amount as 0.01,'' he explains. ''From day to day, the results could vary -- it could be 0.03, or maybe even 0.05'' -- and these ''analytical'' variations may not mean a thing. ''It's important that we don't assume anything or take action on a very low level of PSA. In routine practice, because of these analytical variations from day to day, if it's less than 0. 1, we assume it's the same as nondetectable, or zero.''

I don't know what to believe.

Posted 10/14/2010 12:23 PM (GMT 0)
Chris, I remember reading this from Hopkins within the past couple of years. Personally I agree with Chan...and so does our urologist, the radiation oncologist we met last year, and my husband's "regular" MD.

I had pushed our urologist to perform the ultra sensitive test on John and was told that he didn't believe in it and that it did not provide any truly useful information. He reminded us that when you're recording PSA levels at such fractional levels, you're talking about infinitesimal particles of PSA. Take a PSA test at different times during a single day and you will likely get different readings...kind of like weighing yourself several times a day. That is why I get nervous when I see guys here worry about their PSA going from 0.03 to 0.05, and about the fact that many don't understand that there is no such thing as absolutely no PSA in the bloodstream even after the gland has been removed.
Posted 10/14/2010 12:59 PM (GMT 0)
On the other hand every person who had a biochemical recurrence after RRP had their PSA go from 0.01 to 0.03 to 0.05 to .10 to 0.20. It might take a year or two. It does not instantly jump from 0.00 to 0.20 in a day.

Do you weigh yourself daily or weekly or never? Every 300 pound person was once 150 pounds at some point.
I look at the scale every couple of of days. I use that info to decide if I should eat that extra piece of cake. It is something within my control and obesity is easier to correct if I start now rather than wait until I reach 300 pounds.

I look at the ultra sensitive PSA the same way.
It is better to find any problems early. At least you can begin planning and maybe make some life choices.

A great link posted earlier by An38 shows the other side to the story:
"
See Table 5 in http://www.prostate-cancer.org/education/preclin/McDermed_Using_PSA_Intelligently2.html
Look at See Table 5

where the third generation DMC test provides a post-RP nadir which can be related to the probability of biochemical recurrence. For a reading of <0.01 this is 4%, for a reading of 0.02 it is 16% and for >0.04 it is 89%."

Every one of those individuals included in the study would have received a <0.1 PSA result. Would you want to know if you were in the 4% group or the 89% group? I would. Sometimes what you don't know can harm you.

Does anyone know how old the Johns Hopkins quote is? 6 years ago the ultrasensitive test had more variation than the latest ECLIA test.

What test do you think surgeons request for themselves, friends and family members after RP?

Jeff

Post Edited (Worried Guy) : 10/14/2010 5:57:02 PM (GMT-6)

Posted 10/14/2010 1:21 PM (GMT 0)
Sephie,

I agree with you. My PCP ran my last PSA as ultra sensitive without my knowedgle. As long as it came back <.1 it would not have matter to me. I can understand the interest if someone has an adverse pathological feature and they want to start radiation from a trending upward PSA. But if your PSA is hovering in the <.1 range I would disregard them being anything significant.

I guess my next question would be, is where is the data showing that starting radiation treatment before .1 or close to it improves survival?  Logic would seem to say it does, however we are dealing with biology, not logic and I have seen no studies showing improved survival for starting radiation around .1, does anyone have any?

 

Post Edited (ChrisR) : 10/14/2010 7:35:44 AM (GMT-6)

Posted 10/14/2010 1:57 PM (GMT 0)
Personally I'm on board with the ultra sensitive test, mine comes in as <0.04 I don't know if they "filter" the 0.01 sensitivity or use a mid range test (going to ask Uro' in a couple of weeks) but I want the earliest possible warning of a recurrence.

If you understand and accept the variations inherent in any lab work it's easier, lots of time in the labs in school drove this home. Bottom line is I would have some PSA anxiety no matter what the cutoff point is, with the ultra sensitive I just have an earlier warning.
Posted 10/14/2010 2:32 PM (GMT 0)
Daveshan
Look at my PSA in my old long signature below. I am part of a study comparing the 2006 version of ultrasensitive test to the 2010 version. You can compare the numbers directly as they were taken from the same sample. 0.04 on the 2006 test was <0.01 on the new test. Look at the test results to see which protocol they used.
Jeff
Posted 10/14/2010 2:36 PM (GMT 0)
Thanks Worried Guy, that clears up which test they are probably using.
Best of luck on continued 0.0s
Dave in Durango CO
Posted 10/14/2010 2:54 PM (GMT 0)
Dave,
I think you mean 0.00s ;-)
By the way, the new third generation test does not cost any more than the old. It will eventually replace the second generation tests. Once it becomes widespread there will be plenty of associated studies showing the merits of early warning.
I was in engineering school when calculators first began to replace slide rules. The old school "slide rulers" scoffed at the extra digits. Now look.
Technology advances.

Glad to help.
Jeff (an ex slide rule user)
Posted 10/14/2010 4:35 PM (GMT 0)
I'm a big supporter on the ultra sensitive test. For me it proved it's value. My post op PSA went from <.01 at 3 mons, to .01 at 6mons, .07 at 9 months, to .28 at 12 mons, to .50 at 14 mons. If I had  a normal test I wouldn't have know of the recurrence until my PSA hit .28. If I had also been on a six month schedule my PSA could have been > 1.0 before I knew of the recurrence.
Posted 10/14/2010 4:39 PM (GMT 0)
I'm in the middle of the sensitivity question right now. My last test came back 0.1 after a succession of <0.1. It's not biochemical failure but neither is it zero. I looked at the screen the doctor was reading and there were no extra digits to ask about.
I've a friend who is a pathologist at the lab in the hospital lab and he tells me that they do the ultra sensitive test but the doctors all feel that it just adds anxiety with meaningless changes and they request the results only to the first decimal point.
My next question then was about rounding which, as I suspected, is to the nearest tenth. So, my PSA could still be less than 0.1 but rounded up. So much for removing my anxiety.
Of course with T3b staging my chance of recurrence is very high no matter how they test it. I'd just like to finish paying for the first cure before I start the second.
Posted 10/14/2010 6:42 PM (GMT 0)
STW
When you talk with your doc tell him you want a copy of the report sent to you. There is space for that. The requester can have copies sent to your GP or any other doc you request, including you. You are paying for it, you have the right to the results. The "ultrasensitive test" is called the "diagnostic" test - not the "screening" test. Before you leave the office make sure that box is checked and the "cc results" box has your name in it.
The report will tell you what protocol is used and the complete results. You'll have to be a big boy and round numbers yourself. I think you can handle it. Don't you?

Be thankful you are living in 2010. Twenty years ago the first generation test was good to 1.0. Less than that was considered good.
(By 2015 the ultrasensitive test will be the norm and there will be people looking for 3 digits on an even more selective antigen.)

Good luck
Jeff
Posted 10/14/2010 9:36 PM (GMT 0)
Here is an excerpt from an article on the subject. It references several studies showing earlier detection.
We will have to wait a few years to show the results of long term studies.

http://www.cancernetwork.com/display/article/10165/80768

"Ultrasensitive PSA assays have the potential to allow earlier, more accurate prediction of prostate cancer recurrence after radical prostatectomy. In 1992, it was shown that ultrasensitive assay could have detected a rise in PSA 175 and 581 days earlier than standard assays in two patients who had a clinical recurrence of disease.[36] The ultrasensitive assay detected PSA at levels of 0.1 ng/mL, compared with a 0.3 ng/mL detection limit for the standard assays used. In a subsequent study, PSA recurrence at levels from 0.01 to 0.07 ng/mL (within an average of 569 to 589 days) was correlated with later recurrence of prostate cancer in 23 cases that had apparently been cured (showing no residual prostate cells).[29]

In a study in 148 patients with postoperative PSA values less than 0.1 ng/mL on conventional PSA assays, postoperative PSA increases of 0.1 ng/mL to as little as 0.001 ng/mL detected by ultrasensitive assay correlated significantly with indicators of a poor prognosis, such as positive surgical margins, larger tumor volumes, greater preoperative PSA, and extracapsular extension.[37]

Detectable PSA limits have been lowered by new assays that improve antibody affinity or specificity to ligand or use monoclonal-monoclonal or monoclonal-polyclonal combinations that differ from standard assays. In addition, standard PSA assays have been made ultrasensitive by applying them to concentrated serum.

Using the latter method, Haese et al[38] improved the timing of the detection of recurrence by nearly 300 days, discovering 86% of relapses within 1 year of radical prostatectomy, compared with 25% found by standard assay. Of 422 patients observed from 1 month to 5 years, 88 demonstrated a PSA recurrence (an increase of at least 0.10 ng/mL) by ultrasensitive assay with concentrated serum. Of these, 28 (31%) had recurrence detected by ultrasensitive assay that was subsequently detected on standard assay of native serum. A total of 37 patients (42%) showed evidence of recurrence simultaneously on both assays, and 23 (26%) had recurrence measured by ultrasensitive assay but not on standard assay.

The investigators noted that in the simultaneous detection group, ultrasensitive detection would likely have been achieved earlier if sampling intervals (6 months during the first year and 1 year thereafter) had been shorter. They also speculated that follow-up was likely not long enough to detect recurrence by standard assay in patients with recurrence detected by ultrasensitive assay only."
Posted 10/14/2010 9:39 PM (GMT 0)

Worried Guy said...
 

Does anyone know how old the Johns Hopkins quote is? 6 years ago the ultrasensitive test had more variation than the latest ECLIA test.

What test do the surgeons ask for themselves, friends and family members after RP

The answer to this is that it was written at http://www.phoenix5.org/Basics/psaPostSurgery.html in Winter 2000. I think John Hopkins (and in fact even Patrick Walsh) in his book quote this verbatim but ultrasensitive tests have moved on.

Posted 10/15/2010 12:00 AM (GMT 0)
An38

"It was written at http://www.phoenix5.org/Basics/psaPostSurgery.html in Winter 2000. I think John Hopkins (and in fact even Patrick Walsh) in his book quote this verbatim but ultrasensitive tests have moved on."

Yes they have and so should we.

Thanks for the find. I am bookmarking this thread.

Jeff
Posted 10/15/2010 12:03 AM (GMT 0)
Jeff, I think good data is always important. Bad data can drive you just crazy. I am in a fight with my uro for the ultra sensivite PSA. He does not believe in it. Go figure another battle with mu Uro.,

Cajun Jeff
Posted 10/15/2010 9:19 PM (GMT 0)
The ultra-sensitive PSA test is appropriate for surgery patients who had PSMs, EPE or SVI, or a positive pre-surgery DRE...how's that for alphabet soup!

For the large population of surgery patients who had none of these, the standard PSA test is appropriate. The term "PSA Anxiety" was originally coined specifically for this group who watched the slight, naturally occurring variation in ultrasensitive PSA test results and panicked unnecessarily. [There are, of course, a very small number of exceptions to this and everything else in life...]
Posted 10/16/2010 1:05 AM (GMT 0)
Those are reasonable guidelines.
Unfortunately since I now "enjoy" the trifecta of having 3 out of the 4 indicators in the above alphabet soup, it looks like the 2 digit Gen. 3 test is for me.
(Until they come up with Gen 4 in 2018 or 2019.)

Jeff
Posted 10/17/2010 12:29 PM (GMT 0)
To people who have had a ultrasensitive PSA test immediately post surgery with a 3rd generation DMC PSA test:

Table 5 in the article on using PSA intelligently was derived from the article: http://webdoc.nyumc.org/nyumc/files/urology/attachments/shen_lepor_taneja.pdf

A very interesting fact in the article p778 top right column is that the mean time to ultrasensitive post-op PSA nadir was 10.4 months for the 906 patients in this study. Until I read this study I was not aware of this - I worked completely off the PSA half time of 2-3 days. There is no real explanation provided for this within this article but 906 patients is a substantial number of patients and so this is not a one-off occurance.

Hope this helps someone.

Regards,
An

Post Edited (An38) : 10/17/2010 6:32:23 AM (GMT-6)

Posted 10/17/2010 2:15 PM (GMT 0)
An38 said... ...the mean time to ultrasensitive post-op PSA nadir was 10.4 months for the 906 patients in this study. Until I read this study I was not aware of this - I worked completely off the PSA half time of 2-3 days. There is no real explanation provided for this within this article but 906 patients is a substantial number of patients and so this is not a one-off occurance. Thanks, An.   The half-life of PSA in the bloodstream is between 2 & 3 days.     The prostate is the primary source of PSA in the bloodstream, but even after it is surgically removed, there are other sources which produce very small amounts which may or may not be measurable at the lower detection limits of the ultrasensitive PSA test .   “Saved” neurovascular bundles are among the most well-known and commonly attributed sources, but there are also others.   Of course, remaining cells of prostate cancer might also be contributing to PSA in the bloodstream   After RP, at such low levels, there is a naturally occurring variation in the amount of PSA measured in the blood, plus variations in the measurement technique (known as “gauge R&R”, or repeatability and reproducibility).   Studies have shown back-to-back PSA measurements to vary by hundredths of a ng/mL , which is a significant amount compared to the ultrasensitive PSA test’s lower detection limit .   The mean (average) number of months to nadir in the study you provided was 10.4 for all groups (irrespective of the eventual nadir), but one standard deviation (SD) was 11.0 (a wide distribution).   Elapsed time cannot go into negative months, which reveals that a positively skewed distribution exists.   Perhaps too technical, but all this says to me is that the actual measured PSA results bounced around in some men at very low levels, likely due to naturally occurring variation (biological or measurement) before the rock-bottom nadir was recorded.   The half-life of PSA in the bloodstream is still between 2 & 3 days.     edit:   added sentence “Of course…” Post Edited (Casey59) : 10/17/2010 9:48:13 AM (GMT-6)
Posted 10/18/2010 1:09 PM (GMT 0)
I'm not sure if this is pertinent,but I have read studies that have said, elevated parathyroid hormone levels and elevated PSA levels are related, I discovered this while investigating reasons psa levels can be high [other than caused by PCa]. My brother had issues with parathyroid gland that caused all kinds of strange levels of calcium etc...to be elevated in his system,he was only in his early 20's so psa wasn't tested. Worth checking out in my opinion!
Posted 11/30/2010 8:30 PM (GMT 0)
Just a BTW. You don't have to rely on the Dr to get the test you want these days. I get mine through PrivateMDLabs.com. There are others, google it. Your insurance may not cover it, I never tried it--the cost is not unreasonable, about $75 for the ultrasensitive. I get the results and I give them to the Dr, not the other way round. He doesn't think I need ultrasensitive, I like the extra info--my choice.

 

Posted 11/30/2010 9:44 PM (GMT 0)
Personally, I don't think the ultrasensitive test is needed (There is now a new one in the works that will measure to an accuracy of 0.001 ng/mL). Both my urologist and my primary care physician have used the standard PSA test for all my follow-up PSAs until this year. The lab that my primary care physician uses switched to the ultrasensitive test for all PSAs, including screening, post-prostatectomy, etc. My latest PSA came back at 0.02 ng/mL. Honestly, I at first felt a wave of anxiety but it quickly diminished when I realized that 0.02 is insignificant. More and more labs are using the ultrasensitive test for no good reason. I'm not concerned, nor is my urologist, by a PSA less than 0.1.

Post Edited (TimG) : 11/30/2010 2:50:41 PM (GMT-7)

Posted 11/30/2010 10:38 PM (GMT 0)
Tim:

Mine went from 0.01 to 0.02 to 0.06.

I am not so sanguine, but that's just me, I guess.

You can all tell from my other posts that I am already convinced that the beast is back and I am looking at SRT.

I envy those of you that can TRULY ignore these type of readings.

I am also NOT letting this interfere with daily life activities, but it is always there in the deep recesses of my brain!

Mel

Posted 11/30/2010 10:54 PM (GMT 0)

TimG said...
Personally, I don't think the ultrasensitive test is needed...

My personal advice on selecting standard or ultrasensitive PSA test post-prostatectomy is personalized to one's individual case characteristics.  No two cases are exactly alike, but cases can be effectively categorized for this purpose.

For example, a decently high percentage of cases result in low- or intermediate-Gleason, relatively low PSA, and clear surgical margins.  In these cases, BCR has a low likelihood, and the standard PSA test for post-treatment monitoring is going to be fine in most of these cases, and can help avoid an unnecessary case of "PSA Anxiety" from the naturally occurring variation which is detectable at the low "ultrasensitive" levels.

Cases with PSMs, EPE, SVI, high-Gleason, positive pre-treatment DREs, for example, would be good cases for using the ultrasensitive PSA test for monitoring after treatment.

Do I need to say that I am not a doctor?  No, of course not, but I will anyhow.  I am not a medical doctor.

Posted 12/1/2010 3:47 AM (GMT 0)
I have had Ultrasensitive since surgery, so don't know anything else. I would have higher anxiety now if mine came back <.1. Curiosity would kill me.

Another interesting side note to the JH comments about .2, the test report from the lab which I get from medical records, states that the lab considers .05 as a sign of reoccurence. Who do I believe, the testing lab, or a JH report from 2000 ? I am betting on the lab.
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