PSA and Various Stages

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Herophilus
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   Posted 4/11/2011 12:40 PM (GMT -6)   

I have seen a few topics on here regarding the level of PSA and the corresponding Gleason, and the topic of PSA and relationship to metastatic disease.

The following has been asked:  How can a person with a Gleason 9 and metastatic disease not have a PSA off the charts.  As an example when my father was diagnosed at 70ish his PSA was in the thousands and he had advanced metastatic disease. 

Perhaps we need to consider how the pathologic model regarding cancer works. The pathology description of the cancerous tissue classifies it from well differentiated to poorly differentiated adenocarcinoma.  That is to say that the well differentiated tissue under microscopy looks similar to the source tissue (In our case it is prostate glandular tissue. But it could be breast, colon, or other tissue).  The poorly differentiated tissues have very little in common with the source tissue.  A theory is, that at some point the tissue becomes so poorly differentiated that it is no longer biologically active and does not function like the source tissue, (prostate tissue in our case) and does not produce PSA.  What point this occurs, does  it follow a predictable path…I have not found the answers, however from a completely anecdotal perspective it does makes some since of some of cases that are posted here that I have found puzzling. 

CAUTION some of the following is COMPLETELY UNFOUNDED speculation on my part.  So when metastases occurs regardless if it involves bone or soft tissue the metastatic tissue is still the source tissue, in our case prostate tissue.  As discussed previously on HealingWell it takes lots of tissue to become evident.  When the body has this dramatic increase in volume of prostate tissue the resulting PSA can and often is in the hundreds, thousands, and even tens of thousands.  Perhaps in an individual patient with a Gleason 9, the offending metastatic lesions are composed of a majority of well differentiated tissue and the resulting PSA is off the chart.  Perhaps in a different patient for various reasons, known and unknown, the offending tissue is completely poorly differentiated and a lower PSA is noted.

Dad was a Gleason 9…it was 15 years ago and I honestly don’t remember if anybody actually ever said anything about the composite tissue percentages…X %3, X % 4 and X % 5.  Do the actual answers to these questions make a difference in my case or any case, probably not?   However I have a quest to fully understand this darn disease and because of that I’m always on the hunt.

Hero


zufus
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Date Joined Dec 2008
Total Posts : 3149
   Posted 4/11/2011 5:44 PM (GMT -6)   
Hero- excellent and no doubt we are in the thick of PCa 'no rules in stone', up ahead our first stop the Twilight Zone...where fact and fiction blurrs our logic and realities. (dramatic humor sentence-LOL).

It is in books that some variants or forms of PCa don't give off much or any Psa's to measure...and a patient could have mets happening without the Psa to use as a clue. This is rarer but does happen. Paact Newsletter just out has a gig on Molecular Pathology of PCa, they can test for some genetic causes of any individuals cause for their PCa and even do some targeted therapies based upon such.
 
I have been trying to get others to see how big a deal this righteous Pathology can become...it is not extensively used right now...but growing. Dr. Bonkhoff, Dr. Rubin, Dr. Chinn and some others are more tuned in on all this. Dr. Chinn wrote in the newsletter even same Gleason grade and PCa volumes can have different prognosis's...because of the genetic issues which trump Gleason scores in this mix (paraphrasing it). Most people are all worried about Gleason scores which is a generality of correctness, further analyzed it is more about the genetics level as to how aggressive or indolent is ones PCa or how it might behave even later or to certain therapies (this is known and in Bonkhoff's writings and findings). Dr. Strum has collaborated with Bonkhoff for years and said he was the best in the world, maybe after you read what he can do in pathology...you will undertand he is miles in front of the other experts...and they are good.

Read: http://www.prostapath.org/download/prognostic-predictive-markers.pdf

http://www.nature.com/modpathol/journal/v21/n2s/full/modpathol200811a.html  (Dr. Rubin)
Dx-2002 total urinary blockage from PCa emergency room, bPsa 46.6,
12/12 biopsies all 80-95% vol., Gleasons found 7,8,9's, scans appeared clear, ADT3 prior to Neutron & Photon radiations, DES since 2004-5.

Post Edited (zufus) : 4/11/2011 4:47:39 PM (GMT-6)


John T
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Date Joined Nov 2008
Total Posts : 4268
   Posted 4/11/2011 8:57 PM (GMT -6)   
Hero,
Have you read "Primer on Prostate Cancer " by Dr Stephen Strum? He does a good job of explaining the relationship of PSA and Gleason grade and tumor size. As Zufus mentioned newer genetic markers may explain why some pc does not follow the normal expected progression or the normal relationship of psa and gleason grade.
JT
65 years old, rising psa for 10 years from 4 to 40; 12 biopsies and MRIS all negative. Oct 2009 DXed with G6 <5%. Color Doppler biopsy found 2.5 cm G4+3. Combidex clear. Seeds and IMRT, no side affects and psa .1 at 1.5 years.

logoslidat
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Date Joined Sep 2009
Total Posts : 6048
   Posted 4/11/2011 10:41 PM (GMT -6)   
but if it is a true gleason 9 isn't it by definition poorly differentiated, true the 4 in a soft 9, less so, but still.. I thought it was the poorly differentiated that made it more aggresive. I like source tissue concept tho. I,ve often wondered if a gle 10 aggresiveness matches something like pancreatic cancers agressiveness or breast cancer. I mean even with a 10 it takes some time to kill, unlike, I think, some of the more aggresive such as lung or pancreatic.
Diagnosed 8/14/09 psa 8.1 66,now 67
2cores 70%, rest 6-7 < 5%
gleason 3+ 3, up to 3+4 @ the dub
RPP U of Wash, Bruce Dalkin,
pathology 4+3, tertiary5, 2 foci
extensive pni, prostate confined,27 nodes removed -, svi - margins -
99%continent@ cath removal. 1% incont@gaspass,sneeze,cough 18 mos, squirt @ running. psa std test reported on paper as 0.0 as of 12/14/10 ed improving

zufus
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Date Joined Dec 2008
Total Posts : 3149
   Posted 4/12/2011 6:52 AM (GMT -6)   
In the link I posted above Dr. Rubin's Modern Pathology Journal Article...see page 10 about 'Predictive markers of PCa Progression'. This helps explain what they currently know and working on. Some of the individual molecular biomarkers to predict PCa progression are: MTA1, Muc1, TMPRESS2-ERG fusion PCa. They identified 40 genes in dysregulation and used immunohistorchemistry and found 12 proteins encoding genes that can help distinguish men who die of PCa from those with long-term disease, disease-free survival. So predictive models are coming out in effect...we want them now.

This is the new frontier of knowing about PCa...that was unknown a few years back.
 
This will trump Gleason grading and other less definitives in PCa.

proscapt
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Date Joined Aug 2010
Total Posts : 644
   Posted 4/12/2011 12:49 PM (GMT -6)   
The challenge is that Gleason tries to capture in a single variable a process that apparently has dozens of variables.

Gleason is ONLY about the visual appearance of the cells under the microscope. It is a visual distinction, not a functional or genetic distinction. So by definition a high Gleason cancer is "poorly differentiated".

But there is only a limited correlation between Gleason and whether a cancer is androgen-sensitive, for example. Or whether it has various other features at the genetic or molecular level that make it faster growing or slower growing, susceptible to chemo or insensitive to chemo, responsive to various nutritional interventions or not, able to implant in bone marrow or not, etc.

New research is coming out every week about genetic difference that matter and about the actual chemical pathways that are involved - for erxample how a cancer cell gradually overcomes deprivation of androgen and becomes androgen independence. But this is a rapidly evolving field. So for now we just have to keep in mind that it's complicated.

By analogy, think about the relationship between weight and obesity. On average, people who are heavier tend to be obese, and if said that heavier people have a greater risk of cardiovascular problems, you'd be right. But a 6'5" 250 lb athlete is a very different case than a 5'4" 250 pound person couch potato. As crude as it is, this is what we are dealing with when are trying to map Gleason scores, rates of PSA production, and underlying biochemical mechanisms which affect disease progression. They are different; correlated, yes. but very different.

zufus
Veteran Member


Date Joined Dec 2008
Total Posts : 3149
   Posted 4/12/2011 1:55 PM (GMT -6)   
Pro- well put into laymens terminology and your analogies , you got a decent understanding on this so as to explain it to others and applaud your words on this....if you happen to accept such applause. It is going to get very interesting in the near future.
Dx-2002 total urinary blockage from PCa emergency room, bPsa 46.6,
12/12 biopsies all 80-95% vol., Gleasons found 7,8,9's, scans appeared clear, ADT3 prior to Neutron & Photon radiations, DES since 2004-5.
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