Is the Gleason System Flawed?

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Tony Crispino
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   Posted 9/15/2010 1:10 AM (GMT -6)   
I have some interesting food for thought that somewhat relates to Tud's post on Gleason Scores. I am starting a new thread for this discussion because I want to see if everyone can relate to my thinking on the matter.

This is me thinking outside of the box...

It is my theory that maybe the Gleason Sum of a tumor is not as important as the highest Gleason Grade of a tumor and the size of that grade in the tumor.

Here are my hypothetical patients:
All three are after Post RP pathologies that have been thoroughly examined and there is no evidence of capsular penetration...
In patient A he has a ten gram tumor that is 70% grade 3 and 30% grade 4. He would be a sum of 3+4=7.

In patient B he has the opposite. A ten gram tumor that is 70% grade 4 and 30% grade 3. He is sum 4+3=7.

In patient C he has only a 3 gram tumor that is all grade 4. He is sum 4+4=8.

Here's my trivia:
Why aren't patient's A and B also Gleason Sum of 8? Both have just as much Gleason Grade 4 cells as patient C. The grade 3 cells are likely not going to be the problem. Patient B has far greater grade 4 tumor cells than both A and C combined. Yet he is still Gleason Sum of 7. If I used common sense, Patient A and C are the same risk according to tumor size, and patient B has the highest risk...In fact Patient A could have even higher risk than patient C because he also has additional cancer (let's just call it a large tertiary grade 3).

It is my contention that not just the way we view slides to define aggressiveness is very suspect, but also we are missing the key component of exactly how much of each grade is present.

This one has bugged me since day 1 of my journey...In 4 years I still don't have an acceptable answer...

Which of these patients do you think has the highest risk?
Which do you think has the lowest rish?

I would think that patient C will do the best here, followed by patient A, and it is patient B that has the highest risk factors...

Advanced Prostate Cancer at age 44 (I am 48 now)
pT3b,N0,Mx (original PSA was 19.8) EPE, PM, SVI. Gleason 4+3=7

RALP ~ 2/17/2007 at the City of Hope near Los Angeles.
Adjuvant Radiation Therapy ~ IMRT Completed 8/07
Adjuvant Hormone Therapy ~ 28 months on Casodex and Lupron.

"I beat up this disease and took its lunch money! I am in remission."
I am currently not being treated, but I do have regular oncology visits.
I am the president of an UsTOO chapter in Las Vegas

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Post Edited (TC-LasVegas) : 9/15/2010 7:13:49 AM (GMT-6)

Elite Member

Date Joined Oct 2008
Total Posts : 25393
   Posted 9/15/2010 1:30 AM (GMT -6)   
Tony, now my answer is in both places, but that is ok.

To answer your reply to my last post, I would rank the patients in the same order that you did. Patient B has the most "4" cells by volume and would be at the greatest risk for aggresiveness in my opinion.

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 ?
Latest: 6 Corr Surgeries to Bladder Neck, SP Catheter since 10/1/9, SRT 39 Sess/72 gy ended 11/09, on Catheter #21, will be having Ileal Conduit Surgery in Sept.

Tony Crispino
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Date Joined Dec 2006
Total Posts : 8128
   Posted 9/15/2010 1:41 AM (GMT -6)   
David thank you.
Which patient do you think should be considered the lowest risk?


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Date Joined Mar 2010
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   Posted 9/15/2010 4:30 AM (GMT -6)   
Hello all,

I understood that it is more the proportion of 4/5 not the volume that is the more significant prognostic factor.

Patient A - 30% 4/5, 10g
Patient B - 70% 4/5, 10g
Patient C - 100% 4/5, 3g

Given the higher importance of the proportion I would say that C is the scariest, followed by B and then A. I think that although B has the higher amounts of Gleason 4 cells as C it is surrounded by the tempering effect of the Gleason 3 which "dilutes" the mix. It is a lineball call between the two I think. But patient A is the lowest risk because it has a much better proportion.


Post Edited (An38) : 9/15/2010 6:32:29 AM (GMT-6)

English Alf
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Date Joined Oct 2009
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   Posted 9/15/2010 5:40 AM (GMT -6)   
Good questions, but almost impossible to answer.

I know this topic relates to post-op pathology, but the problem even with post op pathology is that it doesn't show you the time line regarding rate of change.
For me "Risk" relates to how rapidly things are changing. So whatever the Gleason score or PSA score is, what matters has a lot to do with: how long has it been at this level? and if pre op How long will it stay at this level? (Simialrily having just joined the "zero club" my only concern is really how long will I stay in it)

And the problem with keeping an eye on the prostate while it is still in situ is that you can't really: monitoring change is highly complex.
What is possible by way of improvements? For instance is anyone using something like the da Vinci robot system to do keyhole examinations and monitoring of the prostate

My dermatologist has a much simpler job monitoring my moles. (there is Melanoma risk in my family) She can see all my skin, (yes all of it, every nook and cranny) she can count moles, measure them, draw them, take photos, make notes about their shape size and colour and if they are flat or hairy or whatever and every six months she takes another look and if something looks wrong (twice in 13 years) she can remove it and send it to the path lab (negative both times)

Even examining a breast for lumps is quite easy compared to trying to work out what's going on in a prostate.

And I think the location of the tumour is important too. Are Gleason 3 cells right on the margin a bigger risk than grade 4 cells right in the middle of the gland?

And is there a way of keeping the prostate or certain of the cells alive 'in vitro' after surgery etc so as to monitor what they do over time? and would that be any use for anything?

Born Jun ‘60
Apr 09 PSA 8.6
DRE neg
Biop 2 of 12 pos
Gleason 3+3
29 Jul 09 DaVinci AVL-NKI Amsterdam
6 Aug 09 Cath out
PostOp Gleason 3+4 Bladder neck & Left SVI -T3b
No perin’l No vasc invasion Clear margins
Dry at night
21 Sep 09 No pads daytime
17 Nov 09 PSA 0.1
17 Mar 10 PSA 0.4 sent to RT
13 Apr 10 CT
28 Apr 10 start RT 66Gy
11 Jun 10 end RT
BMs weird
14 Sep 10 PSA <0.1
Erections OK

Veteran Member

Date Joined Dec 2008
Total Posts : 3149
   Posted 9/15/2010 6:27 AM (GMT -6)   
Myself find using our logic in PCa is somewhat even flawed, it is less than easily definable. Do you think ploidy analysis, or PCa variants and ones own immune system values...enter into prognosis???? If so how do we measure all that with current technology and how the docs interpret all this while, at the wheel? We can try to use logic and will find some useable value in it, good luck with total definity in PCa, just look at patient histories is a good clue.

Also, it is possible to have missed biopsies, that harbor a different Gleason score, I was a poster child for such (LOL), 3 different ones found and two sets of those even (7,8,9's-2X over). That doesn't need much elaboration to grasp that idea. Do we have definity in our biopsy testings to begin with, then add the other factors I mentioned.

If you find clear cut answers, post the findings and let's see if they hold water or have exceptions and/or how often do we find exceptions. Even the original Gleason scoring thing could be more art than defined science (i.e. compared to the definity of mathematics), thus do you know it is 100% accurate anyway??? Food for thought maybe.
Dx-2002 total urinary blockage, bPsa 46.6 12/12 biopsies all loaded 75-95% vol.; Gleasons scores 7,8,9's (2-sets), gland size 35 normal, ct and bone scans appearing clear- ADT3 5 months prior to radiations neutron/photon 2-machines, cont'd. ADT3, quit after 2 yrs. switched to DES 1-mg, off for 1 yr., controlled so well, resumed, using intermittently, pleased with results

Regular Member

Date Joined Jun 2010
Total Posts : 416
   Posted 9/15/2010 6:31 AM (GMT -6)   
Isn't there a "timing" factor here that will be a constant yet important unknown?
*Isn't it logical that ALL tumors HAVE to be 1 gram before they grow to 2 grams?
*Dont the cells have to deform to a grade 3 before they deform further to 4, then 5?

Hence, if you had a biopsy that showed a 1g tumor with a Gleason 3+3, you could in theory have caught it in it's infant stages, and it could quickly progress into a 10g 4+4... and the only difference between the exact same cancer is the "when" you found it?
First ever PSA test Jan 2010 @ 51 years old. 4.0.
Digital exam in March 2010 showed 1 side hard, other soft.
Biopsy, positive in 3 of 12.
Davinci @ Boston Medical Center, May 17, 2010.
Was suggested prior to it was likely contained.
June 1 advised 3+-4 was really 4+3 per pathology. Pos margins.
Listed on patholgy as PT3, but with extraprostatic extension,
microscopic invasion of the bladder neck, PT3A is perhaps the case.
Catheter removed June 1.. 1 pad/day, doing ok. ED, but not in rush.
Sore as heck down there, but doing much walking with my wife.
To meet with my Uri (1st meeting since) June 17 - 1 mo point, to discuss.
BMC already has me setup to meet with radiology.
Felling a little better each day. Cant tell if my expectancy just went from 10-15 down to 5-7, the information out there appears to be all over the place. I WILL NOT radiate my insides to the point of being a veg for the sake of a few years. QOL is primary to me. Selfish I guess. I pray for all of you as I do for myself, but must remember that i've had a pretty good 50+ years, and know others who have lost their children to disease.. so I dont have the nerve to complain! Update 7/14/2010: When I tried changing this sig a few days after creating it, system was broken. My new rad oncologist are discussing IMRT.. though he says he can see why waiting a bit and watching the PSA on super sensitive basis might make sense. I am leaning towards IMRT.. thinking is my body is pretty strong now, i'm 51, and if I can rid my body of this while trying to minimize the side effects.. I dunno. No really Good answers. When I said I didnt want radiation to the point of being a veg.. I really meant there is a limit as to where I wish to go in order to realize only a small increase in life expectancy.. and not that I am an unreasonable person. I do, after all, have an obligation to my wife and kids.

Regular Member

Date Joined Aug 2009
Total Posts : 374
   Posted 9/15/2010 7:24 AM (GMT -6)   
Interesting theory, Tony. Have you posed this or some version of it to Vogelzang for his take?
Arnie in DE

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Date Joined Jul 2008
Total Posts : 966
   Posted 9/15/2010 8:11 AM (GMT -6)   

My only thoughts do you assess risk when the cancer was removed and was contained. IF the above was correct then each man has equal chance of recurrence. There is so much more information required to assign risk than gleason score alone. But you are on the right track, in that this tib bit of additional information might be helpful, but not for any prognostic value. However if recurrence did occur then I would believe that this information would be useful for diagnostic evaluations.

Just my thoughts.
You are beating back cancer, so hold your head up with dignity
Age 58 at Diagnosis
Oct 2006 - PSA 2.6 - DRE Normal
May 2008 - PSA 4.6 - DRE Normal / TRUS normal
July 2008 - Biopsy 4 of 12 Positive 5 - 30% Involved Bilateral w/PNI - Gleason (3+3)6 Stage T1C
Robotic Surgery Sept 18, 2008
Pathology October 1, 2008 - Gleason 7 (3+4) Staged pT2c NO MX - Gland 50 cc
Seminal Vesicles and Lymph Nodes clear
Positive Margins Right Posterior Lobe
PSA 5 week Oct 2008 <.05
                   3 month Jan 2009     .06
                   6 month Apr 2009     .06
                   9 month Jul  2009     .08
                 12 month Oct 2009     .09 
                 18 month April 2010   .19

Tony Crispino
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Date Joined Dec 2006
Total Posts : 8128
   Posted 9/15/2010 8:37 AM (GMT -6)   
Good morning all, (Good evening An)
7 Answers so far, 6 different than everyone else's. Pretty much what I expected. I'll respond to each so far:

LV-TX ~ I changed the question slightly. There is no EVIDENCE of capsular penetration. What we do know is that many men have contained T2 disease but the Gleason Sum can still indicate which may have already escaped. So, as we see here, many men have contained disease at relapse, but can still have recurrent disease.

Arnie ~ No I have not asked Vogelzang. But perhaps I missed my best opportunity when I met Dr. Bostwick.

BobCape ~ No proof of that at all in the medical community. It is possible to have a Gleason 10 without any sign of light grades. Disease does not necessarily start at smaller grade and progress to more aggressive grades. It is possible for prostate cancer to start at the highest grades.

zufus ~ Absolutely relevant the identified genetic nature of the disease. It might have been smart for me to state that everything else in the tumors was the same, but you and I both know we can't ver prove such a thing. I was assuming an entire prostate post-op as in the question, but no pathologists actually put and entire prostate under a microscope. When they grade a disease post-op they dissected sections under the scope. This may also have to do with why we have so much mystery...

English Alf ~ Meepin cells alive? Interesting concept. Can you imagine that incubator size? Whether the cells are closest to the capsular wall is a pertinent question as well. I don't know how many pathology reports include that information...

An38 ~ Proportion has to be a changing landscape, other wise all grades are the same. Grade 4 is more aggressive than grade 3 so it is natural to assume that it will grow faster than grade 3. Same with grade 5 to grade 4. ~ But you might be on to something as well. There is no question that by being given a Gleason Sum of 8 that patient C is scarier. But I know many men that never had a relapse with G8, 9, 10 sums, while I also know of many men that died of G6 & 7 disease.

All interesting responses. All well thought out. All factors herein probably need to be considered as well. I think I want a microscope. Can anyone send me their


Regular Member

Date Joined Oct 2009
Total Posts : 314
   Posted 9/15/2010 9:03 AM (GMT -6)   

Just to make it more complex, another wrinkle - take my situation for example.  My post-op path report doesn't give percentages, but the largest tumor by far was a 3 + 3; several smaller ones were also 3 + 3; and a slightly larger one was 4 + 3.  End result = I am a 4 + 3, even though I had much more 3 than 4.

Factor in the facts that we have at least two different systems in effect, both called the "Gleason system" (the comparing apples to oranges problem), and that Gleason scoring is far more of an art than a science and I think you are asking for more precision than a Gleason score can provide.

By the way, when I posed this very question a few months ago, Purg said that it was the highest number that counted, regardless of volume.  He has apparently changed his mind.  That's OK - I think we are all taking a fresh look at a lot of things PCa-related, including all the crap that people in white coats tell us.  [I know, I know ... everyone repeat in unison: "Trust your local uro; trust your local uro; don't scare the newbies; don't scare the newbies ....]

In any event, eventually Gleason scores will be nothing more than a curious relic of these "Dark Ages."


Post Edited (Zen9) : 9/15/2010 8:28:04 AM (GMT-6)

Elite Member

Date Joined Oct 2008
Total Posts : 25393
   Posted 9/15/2010 10:19 AM (GMT -6)   

i find all the different answers interesting, but i thought the point of your exercise was just a simple off the hip call. based on your "patients", i purposely didn't try to factor in other factors that you didnt give in the exercise. was that your intent?

to answer your last question to me, again, just face value on what you offered, Even though Patient A and C both have 3 gms of 4, in simple terms since Patient C only has a total tumor size of 3, that is over 2/3rds smaller than the tumor size of A. Keeping it simple, I say Patient C, even though he's a Gleason 8, would be the easiest to treat and a least potential risk.

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 ?
Latest: 6 Corr Surgeries to Bladder Neck, SP Catheter since 10/1/9, SRT 39 Sess/72 gy ended 11/09, on Catheter #21, will be having Ileal Conduit Surgery in Sept.

John T
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Date Joined Nov 2008
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   Posted 9/15/2010 11:09 AM (GMT -6)   
You can't just take the Gleason grade alone and come up with a solution. If the tumors are all contained then the patients will do equally. A tumor, regardless of grade that is fullly contained will never hurt you. It's only when the cells escape and start reproducing in you body does the cancer become dangerous. Gleason scores only estimate the probability of this occurring. If left untreated the G8 will grow faster and dump more aggressive cells into the blood stream. G3 cells grow slowly and also have a hard time establishing footholds in other parts of the body. A mixture of G3 and G4 cells will grow slower than a tumor composed of all G4 cells. The size of the tumor is important as a large tumor will not take as long to penetrate the capsul, nerves or seminal vessicles as a smaller tumor.
So the starting place as well as the growth rate are important in determining when the tumor will breakout as well as the location of the tumor. Smaller tumors at the capsul edge will breakout faster than large tumors in the interior.
Add to this different rates of growth, imune system response and diet, we have various growth rates within the same gleason grade that are hard to predict, and growth rate indicates agressiveness both in the prostate and outside the prostate. The ratio of androgen independent cells to androgen dependent cells is probably more important to length of survival than the ratio of Gleason grade cells. As Zufus says, it is truely a twightlight zone.

64 years old.

PSA rising for 10 years to 40, free psa 10-15. Had 5 urologists, 12 biopsies and MRIS all neg. Doctors DXed BPH and continue to get biopsies yearly. 13th biopsy positive in 10-08, 2 cores of 25, G6 less than 5%. Scheduled for surgery as recommended by Urological Oncologist.

2nd Opinion from Dr Sholtz, a Prostate Oncologist, said DX wrong, pathology shows indolant cancer, but psa history indicates large cancer or metastasis. Futher tests and Color Doppler confirmed large transition zone tumor that 13 biopsies and MRIS missed. G7, 4+3, approx 16mmX18mm.

Combidex MRI in Holland eliminated lymphnode mets. Casodex and Proscar reduced psa to 0.6 and prostate from 60mm to 32mm. Changed diet, no meat and dairy. All staging tests indicate that tumor is local and non agressive. (PAP, PCA3, MRIS, Color Doppler, Combidex, tumor reaction to diet and Casodex, and tumor location in transition zone). Surgery a poor option because tumor is located next to the urethea and positive margin is very likely; permanent incontenance is also high probability with surgery.

Seed implants on 5-19-09, 3 hours door to door, no pain, minor side affects are frequency and urgency; very controlable with Flowmax and lasted 4 weeks. Daily activities resumed day after implants with no restrictions. Gold markers implanted with seeds to guide IMRT.

25 treatments of IMRT 6 weeks after seed implants. No side affects at all.

PSA at end of treatment 0.02 mostly the result of Casodex. When I stop Casodex next week expect PSA to rise. Next PSA in November. Treatments and side affects have greatly exceeded my expectations. Glad to have this 11 year journey finally conclude.


English Alf
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Date Joined Oct 2009
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   Posted 9/15/2010 11:20 AM (GMT -6)   
My idea with keeping the prostate alive in vitro was an attempt to think of a way you could keep tabs on what the tumour would have done had it not been removed (isn't that what we sort of all want to know) ie if it doubled in size in a week in a patient might think they were full of mets, but if it just sat there not changing for years they might be able to conclude that all was equally tranquil on the inside.

As for the quantity of gland that actually gets examined by the pathologist post op, I thought that they arranged the sections to cover just about everything. My prostate was 43 grams (4.5cm X 4.5 cm X 3cm) and they took 26 sections in three planes. (4+3+19). Nineteen slices per 45mm (the maximum width) is about one every 2.3mm so what do they hit and what to they miss on that basis?

And another question is do they take 26 sections as standard regardless of how big the gland is or would they have taken 50 sections for a gland weighing 100gm. Because that's going to be a lot of slides to be analysed


Veteran Member

Date Joined Jul 2010
Total Posts : 3892
   Posted 9/15/2010 11:35 AM (GMT -6)   
Very interesting discussion.. I will add some details about my own case..

My original biopsy report revealed three different Gleason grades, 6, 7, and 9...In the four positive cores (out of 12) one was a 6, two were 7's and one was a 9..The 9 core was 20% cancer...ALL of my docs were in agreement on this one. I would be treated as a Gleason 9 even though the total amount of cancer in the other three cores was considerably greater...The Gleason 9 was the trump card...

But the 3+3, 3+4, 4+3, 4+4 do indeed pose a conundrum which perhaps leads to the wide variability in outcomes...The Gleason scores of two different men can be very similar, but their final outcome is very difficult to predict..
Age 68.
PSA at age 55: 3.5, DRE negative. Advice, "Keep an eye on it".
PSA at age 58: 4.5
PSA at age 61: 5.2
PSA at age 64: 7.5, DRE "Abnormal"
PSA at age 65: 8.5, DRE " normal", biopsy, 12 core, negative...
PSA age 66 9.0 DRE "normal", 2ed biopsy, negative, BPH, Proscar
PSA at age 67 4.5 DRE "normal"
PSA at age 68 7.0 third biopsy positive, 4 out of 12, G-6,7, 9
RRP performed Sept 3 2010

Elite Member

Date Joined Oct 2008
Total Posts : 25393
   Posted 9/15/2010 2:33 PM (GMT -6)   
tony's original exercise was just that, no need for the encyclopedia brigade to come out. these are make believe patients, just make an educated guess on what he was asking, no pre-qualifications. we are not doctors here, and there is no test score to worry about.
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 ?
Latest: 6 Corr Surgeries to Bladder Neck, SP Catheter since 10/1/9, SRT 39 Sess/72 gy ended 11/09, on Catheter #21, will be having Ileal Conduit Surgery in Sept.

Veteran Member

Date Joined Mar 2009
Total Posts : 739
   Posted 9/15/2010 3:07 PM (GMT -6)   
I believe the different percentages of gleason scores within the tumor, is known as the "Gleason differential" This is certainly worth googling here, may clear up some of the misconceptions.
Tony- Interesting topic, but my only comment is that, to be able to compare apples to apples, patient C, should have also had a 10g tumor. like A & B.  Then who do you think would be higher risk !
.................Cheers Kev
Age 52yrs [Gold Coast Qld, Australia]
6 out of 8 cores positive 3 X 60% / 3 X 10%
PSA 4 Gleason Score 3+4=7 Stage T1c
RP 24/12/08
Upgrade Gleason Score 4+3=7 Gleason Differential 60%/40%
Stage T2c Three small foci total volume <10%
Neg Margins and Nodes
Nil - EPE
Dry less than 1 week. ED- okay with Meds.
PSA at 18mths no change remains 0.03
"Everday in Everyway, I get better"

Veteran Member

Date Joined Sep 2009
Total Posts : 3172
   Posted 9/15/2010 4:02 PM (GMT -6)   
I know that this is all hypothetical talk...but if the question was changed from "Is the Gleason system flawed?" to "Is the Gleason system perfect?", there would have been a short, two-letter answer.

Elite Member

Date Joined Oct 2008
Total Posts : 25393
   Posted 9/15/2010 5:02 PM (GMT -6)   
kev, with equal tumor sizes, then Choice C would be the logical "worse case" in this exercise
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 ?
Latest: 6 Corr Surgeries to Bladder Neck, SP Catheter since 10/1/9, SRT 39 Sess/72 gy ended 11/09, on Catheter #21, will be having Ileal Conduit Surgery in Sept.
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