Gleason migration upwards ??

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Sleepless09
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Date Joined Jul 2009
Total Posts : 1267
   Posted 4/28/2011 9:15 PM (GMT -6)   
A friend recently had a breast biopsy, which thankfully turned out benign, and when she asked her doctor about the mass becoming cancer she was told it wouldn't.  A mass was either cancer, or it wasn't.  This mass wasn't and never would be.  Another mass might be, but not this one.
 
All of which got me to thinking about Gleason ratings.  Aside from the fact one pathologist might say "three," and another might say "four,"   ---  the art as opposed to the science  ---  does a three migrate upwards to a four, or a four to a five?  Or, can a four get it's act together and drop to three?  Or is four a four and that's that?  Which, I assume would mean that a cell when it goes wonky goes directly from normal to whatever it is and then stays there.
 
Hmmmmmm?
 
I look forward to the wizards of wisdom here filling me in.
 
In the meantime, I am working on my nutrition.  Tonight it's a nice stiff amber rum from Barbados with a whollop of fresh lime and a splash of diet Coke. 
 
Sheldon  AKA   Sleepless 

April6th
Regular Member


Date Joined May 2010
Total Posts : 264
   Posted 4/28/2011 9:39 PM (GMT -6)   
I am not a wizard of wisdom but was thinking about the same thing.

I have never heard of a biopsy result that was a Gleason 9 that has a very tiny amount of cancer (like 1 core with cancer and less than 10% of the core cancerous).

So logically, it seems that since the 5 portion of a Gleason 9 is not found in the lowest volume cancers, it was not there originally and manifested into the 5 from the less aggressive 3 or 4.

Does this make any sense. Is my premise wrong?

Dan
Here are some of my stats:
Age:54
Father diagnosed with PC at age 72 - wasn't contained to prostate when found in 1992.
My PSA rose from 3.2 to 5.1 over the course of 1.5 years with Free PSA at 25% for the last two tests.
DRE showed no evidence of tumor but Uro thought my prostate was a little large for someone my age
PCa diagnosed 4/6/10 after biopsy on 4/1/10
1 out of 12 biopsy samples was positive with 5% of biopsy sample cancerous
Gleason 3+4
Da Vinci surgery on 6/1/10
Pathology report shows cancer confined to prostate and all other tissue clean
PSA tested on 7/15/10: Zero Club membership card issued (trial membership with 90 day renewal)

Sleepless09
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Date Joined Jul 2009
Total Posts : 1267
   Posted 4/28/2011 9:56 PM (GMT -6)   
Dan, sounds good to me --- I grant you full Wizard of Wisdom status, good until revoked by those knowing more than we do.

Perhaps the answer is that non-cancer mass doesn't turn to cancer, but that mass that is cancer can, and does, upgrade, at least sometimes.

Which, if true, makes me wonder if a four is more likely to become a five, than a three is to become a four, or abnormal tissue, worthy of a two, is likely to become a three.

Thankfully, I've tanked up on a second stiff Bajan amber blessing since my first post above, and will soon be in shape to imagine all sorts of possibilities. Right now, however, I am dealing with a particularly disagreeable lion who has, (best I can tell) taken up residence under my bed making trips, at least safe trips, to the bathroom impossible. Unfortunately, the rum with fresh lime and splash of diet Coke, is settling in my bladder and making demands. Kegel be darned! The real 'exercise' is holding dry while avoiding lion infested bedrooms.

Sheldon AKA Sleepless --- and you'd be Sleepless too if your bladder was this full and you had a lion under YOUR bed.
Age 67 in Apil '09 at news of 4 of 12 cores positive T2B and Gleason 3 + 3 and 5% to 25% PSA 1.5
Re-read of slides in June said Gleason 3 + 4 same four cores 5% to 15%
June 29 daVinci prostatectomy, Dr. Eric Estey, at Royal Alexandra Hospital Edmonton one night stay
From "knock out" to wake up in recovery less than two hours.  Actual surgery 70 minutes
Flew home to Winnipeg on July 3 after 5 nights in Ramada Inn  ---  perfect recovery spot!
Catheter out July 9
Final pathology is 3 + 4 Gleason 7, clear margins, clear nodes, T2C, sugeron says report is "excellent"
 
Oct 1st 09 -- dry at night, during day some stress issues.
Oct 31st padless 24/7 
 
First post op PSA Sept 09  less than 0.02
PSA on Oct 23, 2009 less than 0.02
PSA on Jan 8, 2010  less than 0.02
PSA on April 9, 2010 less than 0.02 
PSA on July 9, 2010 (one year) less than 0.02
  

logoslidat
Veteran Member


Date Joined Sep 2009
Total Posts : 5646
   Posted 4/29/2011 12:24 AM (GMT -6)   
I believe it can but , but just heard that somewhere.........
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

logoslidat
Veteran Member


Date Joined Sep 2009
Total Posts : 5646
   Posted 4/29/2011 12:25 AM (GMT -6)   
oops!
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

logoslidat
Veteran Member


Date Joined Sep 2009
Total Posts : 5646
   Posted 4/29/2011 12:28 AM (GMT -6)   
My first post trumps the 2nd turn
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

Ed C. (Old67)
Veteran Member


Date Joined Jan 2009
Total Posts : 2457
   Posted 4/29/2011 7:26 AM (GMT -6)   
Sheldon,
My biopsy showed 2 out of 12 Gleason 8 between 10% and 20%.
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, 21, 2 years <.008? ) undetectable
27 months: .005

zufus
Veteran Member


Date Joined Dec 2008
Total Posts : 3149
   Posted 4/29/2011 7:28 AM (GMT -6)   
Dr. Chinn just mentioned in recent paactnewsletter on Molecular Pathology that Dr. Gleason the inventor of the system, even had trouble identifying his own scorings...not simplistic..more of art. Even the dumb DRE exam (probing as it is), it has become an art and some docs are better at the 'touch' than others (no joke intended...but if you like laughs on that one, I would definitively jump into that howling).

Here are some things that can change in PCa: ploidy DNA analysis (3 scenario types/classifications) diploid is best(like normal cells dual paired sets of chromosomes), it can change to tetraploid (chromosomes not is equal pairs any more but close), could change to aneuploid (the worst and random chaos in chromosomes, some incomplete with broken chains, bizarre amounts and uneven/odd number sets and such). It is known that aneuploid found testings, patients do not respond as well on drugs and have basically a risker prognosis. This can be tested for by like Dr. Bostwick, Bonkhoff, Uro-Cor, maybe Oppenheimer and a select few others that are master pathologists.

You have atleast 24 variant types of PCa, not easily known or identifiable by all patho-docs (this is a problem....not mentioned to us patients....ask your uro doc how many types of PCa have been found????) (link at yananow.net)

Your receptors on the PCa (androgen receptors) can morph and change(very typical over time periods) to whereby the androgen controlling drugs no longer work, the PCa has become refractive called Hrpca, thus your PCa has changed and is much harder to control via drugs or other protocols perhaps. (see www.hrpca.org )

If you want a heavy duty doseage of what we are dealing with in PCa's, read this on pathology, which is the most definitive information on your PCa that could be analyzed or known at this juncture:
http://www.prostapath.org/download/prognostic-predictive-markers.pdf 
http://www.nature.com/modpathol/journal/v21/n2s/full/modpathol200811a.html   

Some one else could maybe find links to Gleason migration or changes. Note: even Gleason 9's vary in which one is overly aggressive compared to another (Dr. Chinn-paactnewsletter) No wonder we see a Jungle in PCa scenarios, it is not simplistic or easily defined.

Post Edited (zufus) : 4/29/2011 7:36:56 AM (GMT-6)


tatt2man
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Date Joined Jan 2010
Total Posts : 2840
   Posted 4/29/2011 8:55 AM (GMT -6)   
interesting article on changes to perception of gleason score - upward migration of results -
www.prostate-cancer.org/education/staging/Luthringer_GleasonGradeMigration.html
internet source said...
In summary, our observations appear to confirm a trend to the upgrading of prostate cancers using the Gleason grading system and, as described in the studies above, may result in the appearance of improved outcomes for prostate cancer patients.



and here is another article-
jnci.oxfordjournals.org/content/97/17/1236.full

...

Post Edited (tatt2man) : 4/29/2011 9:00:16 AM (GMT-6)


tarhoosier
Regular Member


Date Joined Mar 2010
Total Posts : 481
   Posted 4/29/2011 8:58 AM (GMT -6)   
My oncologist mentioned in passing that for men who die of prostate cancer that regardless of the G score at diagnosis, no matter how many years before, their gland and metastases at autopsy are all G4 and 5. De-differentiation, G migrations and mutation are what cancers do.
It is possible to have wide metastases at diagnosis with the sampled tumor cells as G3, but even these men often respond for extended periods (years) before final progression. Evolution at the cellular level is real.

zufus
Veteran Member


Date Joined Dec 2008
Total Posts : 3149
   Posted 4/29/2011 1:50 PM (GMT -6)   
tatt- A+ good right on question link and PCRI site, usually good stuff there

tar- that is interesting what your onco stated, let's hope we don't see anyone with G3 and wide mets...that should be very rare.

ralfinaz
Veteran Member


Date Joined Jan 2011
Total Posts : 735
   Posted 4/29/2011 5:14 PM (GMT -6)   
tarhoosier said...
My oncologist mentioned in passing that for men who die of prostate cancer that regardless of the G score at diagnosis, no matter how many years before, their gland and metastases at autopsy are all G4 and 5. De-differentiation, G migrations and mutation are what cancers do.
It is possible to have wide metastases at diagnosis with the sampled tumor cells as G3, but even these men often respond for extended periods (years) before final progression. Evolution at the cellular level is real.


Tarhoosier has it right. The Gleason Score system graded cancers by their stage of de-differentiation. For a more detailed explanation visit:
http://tinyurl.com/3zloy34

RalphV
Phoenix, Arizona
Surviving prostate cancer since 1992. RP; Orchiectomy;
GS (4 + 2); bilateral seminal vesicle invasion; tumor attached to rectal wall. Last PSA September, 2010: <0.1 ng/ml
Laughter is the best medicine!
www.pcainaz.org/phpBB304

Fairwind
Veteran Member


Date Joined Jul 2010
Total Posts : 3626
   Posted 4/29/2011 7:10 PM (GMT -6)   
My U-doc told me that different Gleason cancers were BORN that way and he thought they STAYED the way they were born. A Gleason 6 can be counted on to remain a Gleason 6. But prostate cancer tends to be multi-focal. You don't just have one tumor, you probably have six tumors and you can't count on the biopsy to find them all. Each tumor can be a different grade..3, 4 or 5

That's why, when they biopsy the entire organ after a prostatectomy, frequently, they find more aggressive cancer than the original biopsy did...
Age 68.
PSA age 55: 3.5, DRE normal.
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 3rd 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. 2-15-'11 PSA 0.0

ralfinaz
Veteran Member


Date Joined Jan 2011
Total Posts : 735
   Posted 4/29/2011 8:26 PM (GMT -6)   
Fairwind said...
My U-doc told me that different Gleason cancers were BORN that way and he thought they STAYED the way they were born. A Gleason 6 can be counted on to remain a Gleason 6. But prostate cancer tends to be multi-focal. You don't just have one tumor, you probably have six tumors and you can't count on the biopsy to find them all. Each tumor can be a different grade..3, 4 or 5

That's why, when they biopsy the entire organ after a prostatectomy, frequently, they find more aggressive cancer than the original biopsy did...


Fairwind,
Biopsies not always depict a true story, but I do not think that aggressive cancers are born that way. One reason is that when cancers are detected by autopsy in young men who experienced an accidental death the tumors found are small and well differentiated. That is they tend to be low Gleason grade. A second reason is based on the work of Dr. Tribukait.

Dr. B. Tribukait and coworkers in Sweden have supported the multi-step progression of prostate cancer with their work on successive needle aspirations of prostate tumors. They evaluated the yearly rate of mutation accumulation as determined by DNA ploidy measurements. In each cell of their bodies, except their germ cells, humans have 23 pairs of chromosomes that dictate the person’s genetic makeup. Normal cells containing 23 pairs of chromosomes are said to be diploid. Dr. Tribukait was able to show that, as time goes by and mutations accumulate, there is a loss or gain of chromosomes in prostate tumors. This process changes the cells from diploid to aneuploid. Aneuploid cells are cells containing an abnormal number of chromosomes. There is a close relationship between DNA ploidy and Gleason Grades. Higher Gleason Grades are mostly aneuploid and tend to metastasize or invade local tissues more readily.

RalphV
Phoenix, Arizona
Surviving prostate cancer since 1992. RP; Orchiectomy;
GS (4 + 2); bilateral seminal vesicle invasion; tumor attached to rectal wall. Last PSA September, 2010: <0.1 ng/ml
Laughter is the best medicine!
www.pcainaz.org/phpBB304

Purgatory
Elite Member


Date Joined Oct 2008
Total Posts : 25364
   Posted 4/29/2011 8:38 PM (GMT -6)   
I fully agree with Ralph's last post. This is in line with my oncologist's point of view on the subject. All cancers, regardless of being PC or not, are all about mutation. The sub-types of PC cancer, is one factor in determing how quickly or slowly further mutation and change in Gleason occur. For many men, they would never naturally live long enough to see type 3 cells mutate to 4 or 5.

And biopsies, I stand by my original view, that its just an estimate at best, a starting point of where a person's cancer is at, and to what extent its mutation is at that moment. And even with the best pathologists at work, and even with second opinions, there will always be a subjective nature to the one viewing the slides.

Better testing at dx, is what is still needed. I hope it will come one day, for future generations of men getting a PC dx.

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 margin
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, 2/11 1.24, 4/11 3.81
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 9/10

Fairwind
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Date Joined Jul 2010
Total Posts : 3626
   Posted 4/29/2011 9:57 PM (GMT -6)   
It's a difficult question..Many men begin as Gleason 6 and stay Gleason 6 for decades..30, maybe 40% of prostate cancers fall into this group. In other less fortunate men, the Gleason 4 and 5 scores show up on the original biopsy, sometimes after multiple negative biopsies...As soon as the PSA moves above normal, Boom, there it is, Gleason 9 right out of the starting blocks. It didn't slowly evolve into Gleason 9 from Gleason 6...It began as Gleason 5 cells right from the very beginning..Next door, a few millimeters away, can be a low-grade Gleason 6 tumor....The grade 3 and the grade 5 tumors can be born at the same time...
Age 68.
PSA age 55: 3.5, DRE normal.
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 3rd 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. 2-15-'11 PSA 0.0

zufus
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Date Joined Dec 2008
Total Posts : 3149
   Posted 4/30/2011 5:23 AM (GMT -6)   
Ralph's link herein a clickable event to make it easier:
http://tinyurl.com/3zloy34  
 
Also while you are there consider joining or looking at the website:
www.pcainaz.org   (also has some photos on Gleason 7,8,9's and PNI)   smilewinkgrin

tarhoosier
Regular Member


Date Joined Mar 2010
Total Posts : 481
   Posted 4/30/2011 7:37 AM (GMT -6)   
Fairwind, I think that perhaps what the doctor was referring to was that G6 cells divide and multiply at a rate nearly that of normal cells. Their apoptosis (rate of death) is also only slightly slower than normal cells. This means that a G6 tumor will grow slowly. We know without doubt that G6 PCa is unlikely to be lethal, at least for many years. This rate of growth and reduced rate of death means that the mutations inevitable in all human cells will occur slowly as the cell division process glides along at a near normal speed. This is what makes this type of cancer indolent. Indolent cells, by definition tend to remain indolent. {Indolent teenagers tend to remain indolent ;}

ralfinaz
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Date Joined Jan 2011
Total Posts : 735
   Posted 4/30/2011 1:57 PM (GMT -6)   
Fairwind,
That many men are diagnosed with low grade cancer these days GS <6 or 6 doesn’t mean that the carcinogenic process started at that level of dedifferentiation. Although the cause of the process is not fully understood, those men went through a carcinogenic process that involved a change in the cells’ chromosome content. This change in ploidy is highly associated with the dedifferentiation process. The proliferation process can be slow, but given enough time it can progress to more dedifferentiated stages and develop a metastatic character.

In a previous post you also mentioned that GS 6 stays GS 6 for decades. I have never seen reported histological evidence of this. What I have read is that untreated prostate cancer when diagnosed at an early age has a high mortality rate. For low grade PCa to kill it has to evolve into a more aggressive cancer becoming metastatic and invading organs and bone. PCa’s progression rate is variable and the disease is diagnosed mostly at an advanced age. Many men die of something else and not of their PCa if the disease progression is slow. This s not to say that there is never progression. I see such men at the support group level when their treatments fail and there is not an effective therapy to stop progression.
Phoenix, Arizona
Surviving prostate cancer since 1992. RP; Orchiectomy;
GS (4 + 2); bilateral seminal vesicle invasion; tumor attached to rectal wall. Last PSA September, 2010: <0.1 ng/ml
Laughter is the best medicine!
www.pcainaz.org/phpBB304

logoslidat
Veteran Member


Date Joined Sep 2009
Total Posts : 5646
   Posted 4/30/2011 2:14 PM (GMT -6)   
To me migration is common sense, the other is wishful thinking. Doesn't mean the migration is a constant, As there could be levels of migration agressivness as well as levels of cell aggresivness.
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

logoslidat
Veteran Member


Date Joined Sep 2009
Total Posts : 5646
   Posted 4/30/2011 2:15 PM (GMT -6)   
Zufus pni or pin, these 2 are swapped routinely, mistakenly
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
Veteran Member


Date Joined Dec 2008
Total Posts : 3149
   Posted 4/30/2011 8:07 PM (GMT -6)   
Logo- what was the context again??
PNI- Perineural invasion (blood source invaded by biopsy needle and found)
PIN-  Prostate-intraepithelial-neoplasia (lol) cells starting to show differentation from normal prostate cells, HGPIN (called High Grade PIN) associated even more so with pre-cancerous PCa scenario (I read somewhere that HGPIN has been associated with aneuploid DNA status for ploidy, and that seemed rather odd???)

Post Edited (zufus) : 4/30/2011 8:11:49 PM (GMT-6)


logoslidat
Veteran Member


Date Joined Sep 2009
Total Posts : 5646
   Posted 4/30/2011 9:15 PM (GMT -6)   
Zufus, the last one with the 2 links. I shudda just gone to the link and find out myself, but I like talk story some time. Fairwind, I due agree with you on the Gl9 observation. Alot of the younger guys seem to get gleason 9 and that certainly didn't migrate. I guess this is why its so tough to conquer cancer all these years, there has to be a common thread among them all, other than splitting of cells.
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

Sleepless09
Veteran Member


Date Joined Jul 2009
Total Posts : 1267
   Posted 5/2/2011 11:00 AM (GMT -6)   
I want to give a warm thanks to all who contributed to this thread, and to my education. I've read the replies, and the links. All much appreciated.

Sheldon AKA Sleepless
Age 67 in Apil '09 at news of 4 of 12 cores positive T2B and Gleason 3 + 3 and 5% to 25% PSA 1.5
Re-read of slides in June said Gleason 3 + 4 same four cores 5% to 15%
June 29 daVinci prostatectomy, Dr. Eric Estey, at Royal Alexandra Hospital Edmonton one night stay
From "knock out" to wake up in recovery less than two hours.  Actual surgery 70 minutes
Flew home to Winnipeg on July 3 after 5 nights in Ramada Inn  ---  perfect recovery spot!
Catheter out July 9
Final pathology is 3 + 4 Gleason 7, clear margins, clear nodes, T2C, sugeron says report is "excellent"
 
Oct 1st 09 -- dry at night, during day some stress issues.
Oct 31st padless 24/7 
 
First post op PSA Sept 09  less than 0.02
PSA on Oct 23, 2009 less than 0.02
PSA on Jan 8, 2010  less than 0.02
PSA on April 9, 2010 less than 0.02 
PSA on July 9, 2010 (one year) less than 0.02
  
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