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Gleason vs. PSA Values at Biopsy? Is There Any Relationship?

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Posted 6/18/2018 8:32 PM (GMT 0)
O.K., so, this is probably a question better-suited for the GS-9/10 Group, but I'm going to post it here in hopes of getting some broader exposure to the question, which is this . . .

With a personal Gleason score of GS-8/9, and with relatively high pre- and post-biopsy PSA values (i.e., 15, 40, 67, etc.), I'm a bit puzzled by the relationship (if any) between those two indicators, and particularly, by the apparent 'lack' of any such relationship in many "high risk" PCa patients.

As my urologist has said, the Gleason score is a clear indicator of just how aggressive the cancer itself is, and one would certainly think that (like me), most high-Gleason folks would have an equally elevated PSA history. Yet there are countless GS-9/10 patients out there with initial PSA values at time of biopsy that are < 10 ng/dL.

How and why do you suppose this lack of correlation exists? In other words, if the cancer is as aggressive as a GS-9/10 rating would seem to indicate, why aren't nearly all of those individuals showing equally elevated PSA values shortly before or after biopsy? Am I simply over-thinking it? For example, is it strictly because they might have been detected early (or earlier) than others? Or do you think there's something else going on there?

Thanks to all.
Posted 6/18/2018 9:02 PM (GMT 0)
It my understanding that the higher the gleason the more psa the cells put out. And as with a lot of things in medicine...it's a correlation that's not perfectly linear. (guide markers, as opposed to GPS)
Posted 6/18/2018 9:05 PM (GMT 0)

island time said...
It my understanding that the higher the gleason the more psa the cells put out. And as with a lot of things in medicine...it's a correlation that's not perfectly linear. (guide markers, as opposed to GPS)


Tall Allen knows all about this, but I believe that the above 'statement' is not correct.
Posted 6/18/2018 9:10 PM (GMT 0)
It is the opposite. A G 6 expresses about 3 to 5 times as much PSA for the same cancer tumor volume compared to a G9 or 10. Some high grade expresses little if any PSA. A friend had a 7 year fight against G9 that was metastatic and his PSA was never above 1 even after he stopped treatment.

Both PSA and G can indicate different risk levels. Any PSA over 20 is high risk even with low G. Conversely a PSA of 1 with a G8 or more is high risk.

So the PSA and G are not directly correlated.
Posted 6/18/2018 10:21 PM (GMT 0)
There are lots of variables here..There is no direct correlation between the two.. But since the higher Gleason grades are more aggressive, they tend to produce higher PSA numbers..On the other side, the more aggressive high Gleason cancers sometimes stop or greatly reduce producing PSA which makes using that yardstick unreliable, especially after the cancer metastasizes..At that point, doctors rely more on scans to judge how far the cancer has advanced...
Posted 6/18/2018 11:24 PM (GMT 0)
My Uro said the size of the prostate in combination with amount of cancer plays into it also. My PSA has never been higher than 2.7 with a mix of 3+3, 3+4, 4+3, and one jackpot 4+4 with a small prostate.
Posted 6/19/2018 1:50 AM (GMT 0)
Well I just learned this the other day from TA. but BPH pumps out the PSA big time too. few years ago My PSA was 21 with a g3+3.. took Finasteride for a few months and PSA 2.6.. Ed
Posted 6/19/2018 4:27 PM (GMT 0)
Thanks to all who rsponded here. Collectively, these comments support what I was saying, that there really seems to be no direct correlation between the two indicators, or a minimal one at-best, and I find it interesting that something fairly innocuous like Propecia/Finasteride could change the PSA value so dramtically, so quickly.

I say this because one of the things that prompted me to post this thread to begin with, was an inexplicable PSA result of my own recently. My PSA value prior to biopsy was 15 (01/18), followed by 43 post-biopsy (04/18), then a high of 69 just 30-days later this past month (05/18). But a full month has since gone by and the most recent PSA value (just 7-days ago or 2-days prior to beginning Casodex), was an unchanged 68. That's roughly 30-days with no significant change (69 to 68), and this struck me as being a little odd, since it had risen nearly 50% in the previous 30-day period (43 to 69).

Anyway, thanks again to all for the responses here. Although far from statistically significant, this short little survey has been somewhat insightful for me. It essentially confirms what I'm slowly but surely learning, and that is . . . prostate cancer has to be one of 'thee' most complex, most diverse, most inconsistently behaving forms of cancer known to man.
Posted 6/19/2018 5:09 PM (GMT 0)
My PSA that started all of this was 6.75 and initial path G 10, final path G 9. I have often asked my Drs and this forum is there any other testing I should have done and the reply answer is PSA test is it. I guess Time will tell if my PSA rises to a point where something else is looked at.
Posted 6/19/2018 5:25 PM (GMT 0)

ntzguy said...
My PSA that started all of this was 6.75 and initial path G 10, final path G 9. I have often asked my Drs and this forum is there any other testing I should have done and the reply answer is PSA test is it. I guess Time will tell if my PSA rises to a point where something else is looked at.

Righto! You're a perfect example of what I'm saying here and this is at the heart of my confusion on this. A GS-9/10 (like yours) or a GS-8/9 (like mine), are both "aggressive" in nature, period! At least that's what we're told, and yet, your PSA remains relatively low. On its face, that's seems inexplicable to me.

Can I ask . . . when was your initial dignosis and what is your current (or most recent) PSA?
Posted 6/19/2018 5:54 PM (GMT 0)
Initial diagnosis August 2015, a couple of weeks after turning 57

Surgery October 12, 2015, radiation completed aearly spring 2016

Had first non-detect 10/18/16 followed another 3/2/17 and then the non-detect fell off at .020. URO pushed visits out to 6 months. Last draw was 12/17 and came in at .026. I work out of town so next appointment is 3rd week of July with a URO closer to home

Guys on this site recently told me just get a PSA anywhere

So I guess Psa is it and it don’t matter where you get it. If the blood pressure tester at Walmart would do a PSA I guess I should go there
Posted 6/19/2018 6:01 PM (GMT 0)
See my signature. It has always concerned me how they are going to tell if I have BCR. My MO at University of Washington says that I should start to be concerned if my PSA reaches 1.0 instead of the standard 2.0. We will start scans at that time as he feels I may have low PSA producing high grade PC.
Also see this....

https://www.healio.com/hematology-oncology/prostate-cancer/news/in
Posted 6/19/2018 6:26 PM (GMT 0)

Artist Mark said...
See my signature. It has always concerned me how they are going to tell if I have BCR. My MO at University of Washington says that I should start to be concerned if my PSA reaches 1.0 instead of the standard 2.0. We will start scans at that time as he feels I may have low PSA producing high grade PC.
Also see this....

https://www.healio.com/hematology-oncology/prostate-cancer/news/in

Thank you! But the link provided (above) appears to be invalid.
Posted 6/19/2018 6:36 PM (GMT 0)

Artist Mark said...
See my signature. It has always concerned me how they are going to tell if I have BCR. My MO at University of Washington says that I should start to be concerned if my PSA reaches 1.0 instead of the standard 2.0. We will start scans at that time as he feels I may have low PSA producing high grade PC.
Also see this....

https://www.healio.com/hematology-oncology/prostate-cancer/news/in

Thanks Mark! Those PSA values are absolutely amazing, given the 'aggressive' nature of the biopsy results. They serve to further reinforce the confusion about the relationship (if any) of PSA to biopsy/Gleason, and of course, we have the exact opposite phenomenon out there as well, whereby some folks have no reported cancer whatsoever (negative biopsies, BPH, etc.), with PSA values that are off the charts. I wish I was smart enough to make any sense of it, but alas, I am not. However, my interest in this is definitely going to continue - its just something that doesn't quite make sense to me.
Posted 6/19/2018 7:50 PM (GMT 0)
- Balladeer
Some more info. There is a prognosis value in the PSA level. There is not a linear relationship between PSA and prognosis for high-grade disease (as it is for low-grade disease). For high-grade disease the relation between PSA and prognosis is U-shaped. Low PSA (<4) has the same risk as those with a high PSA (>20). Medium PSA has lower risk. Very high PSA has the highest risk.
Posted 6/19/2018 8:25 PM (GMT 0)

Gemlin said...
- Balladeer
Some more info. There is a prognosis value in the PSA level. There is not a linear relationship between PSA and prognosis for high-grade disease (as it is for low-grade disease). For high-grade disease the relation between PSA and prognosis is U-shaped. Low PSA (<4) has the same risk as those with a high PSA (>20). Medium PSA has lower risk. Very high PSA has the highest risk.

Interesting! I'm sure its out there somewhere, but I have yet to see or find anything quite like this 'U' shaped relationship reported or discussed elsewhere, and it sure seems to hold true if one looks at the numbers in-general. I haven't seen too many low-grade disease examples with medium PSA values, but there's certainly loads of high-grade disease folks (GS-8/9/10), with both low and high PSA values. That's just outright perplexing!
Posted 6/19/2018 9:10 PM (GMT 0)
Q: Gleason vs. PSA Values at Biopsy? Is There Any Relationship?


A: Yes. Important point to understand first is that PSA value is not specific to Prostate Cancer. It can be, and usually is, affected by several common (benign) conditions. You can tell how much PSA is the "normal" value thrown off from the prostate based upon size, but what you will never know is how much additional PSA is from BPH, prostatitis, and prostate cancer contributions. So in that regard, the statistical exercise you ask about immediately has a large caveat.

None the less, someone has measured PSA values and plotted them against Gleason Scores from PR specimens, and from a pure statistical perspective there is a moderately strong correlation amongst the relatively small set (74 samples) of data. That pattern is clearly visible in the chart on the left.

https://openi.nlm.nih.gov/detailedresult.php?img=PMC4090007_pone.0102156.g002&req=4

Before anyone jumps in saying "Wait, my case of GS=x had a higher (or lower) PSA than any of those shown on the chart," know that obviously more data would result in some PSA points likely to be both higher and lower at each GS, but (recalling the Central Limit Theorem) it would also result in even more data points falling close to the small set of data already collected and the trending pattern is likely to continue.

In summary: The correlation between PSA and GS was moderately strong and highly significant.
Posted 6/19/2018 9:17 PM (GMT 0)
Another similar chart here (lower left quadrant):

https://www.researchgate.net/figure/Serum-ferritin-and-PSA-levels-in-prostate-cancer-and-control-patients-A-and-B-The_fig1_313254627

In this case, the distribution of PSA values is shown for each GS; different study, much larger sample size (several hundred samples for each GS, except only 19 at 5+5). The same positive correlation value is evident (listed in the report as 0.3; weaker correlation than the previously posted small sample study) by observing the the continually increasing median values (heavier black lines in the center of each box) left-to-right with increasing GS. The range of values at each GS is, I think, interesting.


Men with high GS and low PSA are minimally in the bottom quartile of the distributions, and may be statistical outliers. In other words, most men with high GS also have high PSA.

Post Edited (Normal59) : 6/19/2018 3:31:29 PM (GMT-6)

Posted 6/19/2018 9:28 PM (GMT 0)

Balladeer said...
Interesting! I'm sure its out there somewhere, but I have yet to see or find anything quite like this 'U' shaped relationship reported or discussed elsewhere, and it sure seems to hold true...

Clinical and Genomic Characterization of Low–Prostate-specific Antigen, High-grade Prostate Cancer
Posted 6/19/2018 10:44 PM (GMT 0)
It's good to see this thread getting some balance. Leaving it at "No correlation between PSA and prostate cancer aggressiveness" is enough to make docs who say...."Stay off the internet!"...sound down right genius.

When someone finds me 100 patients with psa's of 1000 who has nothing but G6...let me know.
Posted 6/19/2018 10:48 PM (GMT 0)
Strum's book, A Primer on Prostate Cancer has a formula that relates psa to Gleason grade per cc of tumor volume. You have to subtract the normal psa generated by normal prostate tissue.
A very high psa with a high Gleason is usually reflective of psa thrown off by multiple tumors in the lymphatic system.
Posted 6/19/2018 10:54 PM (GMT 0)
Wow! Thank you, gentlemen! Lots to read and absorb here, and it'll likely take me a few days to do so, but this is definitely a deeply fascinating and largely unexpected phenomenon. Like me, and presumably most other casual observers, these various researchers all seem to have identified the trend, yet they don't seem to be able to attribute a specific cause to it. Very, very weird.
Posted 6/20/2018 12:01 AM (GMT 0)
See also Fig. 1 of this study, where the red line is "aggressiveness," which is defined as Gleason>7.
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