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Old 02-06-2008, 03:19 PM   #1
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Thumbs up Gleason 8 (and higher) cancer: not good, but not always the end of the world

The one good thing about my biopsy report and case in December 1999 was that I had a Gleason Score of 7 (4+3). It was right next door to an 8, but wasn't an 8 or higher. But since I'm so close to an 8, I've paid attention to what an 8 means and to developments. (I'm a fellow survivor - no enrolled medical education.)

One of our recent participants is dealing with Gleason 8 cancer and it's discouraging aspects, but I thought this thread could cover some good news as well as not so good news, and better to start a new thread where it would be easier for others to find information about Gleason 8 and higher prostate cancer.

Here's what I consider a piece of encouraging news for Gleason 8 patients whose cancer appears to have been caught early, before it had much chance to grow and spread.

A research team at Johns Hopkins looked into "prostate specific survival" after recurrence following radical prostatectomy. "Prostate specific survival" means living or at least not dying due to prostate cancer; death due to other causes is not counted. This team included some very well-known and highly respected doctors, including surgeons Dr. Patrick Walsh, MD, Dr. Alan Partin, MD, (responsible for the "Partin Tables"), and medical oncologist Dr. Mario Eisenberger, MD. The lead author was Dr. S. Freeland.

Their report, available from Johns Hopkins' "James Buchanan Brady Urological Institute" in a patient-friendly version with a fairly simple table, is highly informative for RP patients concerned about a potential or actual recurrence. The report shows that some patients are at very little risk even if they do nothing, while others are at very great risk. The researchers found the risk depended mainly on how soon they recurred (defined here as reaching a post operative PSA of .2, either within three years of surgery - not good, or at more than three years of surgery - good), whether their post operative pathology Gleason was less than 8 (good, of course) or 8 to 10 (not so good), and how fast their PSA was doubling, the doubling time being the major clue, and the longer the better, with greater than 15 months being the best category (and <3.0 months the worst). The table is broken down into three parts showing 5 year, 10 year and 15 year estimated survival. (There's a small flaw in the table: the second and fourth results columns are headed "Gleason sum >8"; when you read the actual study, it's clear the heading should be "Gleason sum =>8," meaning "equal to or greater than 8.")

Also, remember that some patients in the high Gleason category had Gleason Scores even higher than 8.

Of course, some Gleason 8 or higher patients did not recur at all. Their PSAs stayed below .2, and they did just fine. They were not included in the study. But looking just at the 15 year survival table for those who did recur, if the patient did not recur until more than three years after surgery, and if his PSA doubling time was greater than 15 months, then prostate-specific survival at 15 years after surgery was estimated at 87&#37;! That strikes me as an excellent number for a risky cancer. Moreover, while the firmness of that number is based largely on how many patients in the study fit that category, the estimated range for the "true" percentage was from 79% to 92%. That's a fairly tight range, considering, and it leads me to believe that there were quite a few such patients in the study.

Even for Gleason 8 or greater patients who recurred before three years, if their PSA doubling time was greater than 15 months, 62% of them had still not died from prostate cancer at the 15 year point (range 32% to 85%, the big range suggesting there were not many patients in this category).

This information suggests to me that a Gleason 8 or higher patient can do very well with surgery IF his cancer is confined to the prostate. It also indicates that cancer was confined for many Gleason 8 or higher patients in the Johns Hopkins study.

One final thing needs to be mentioned. At the time most of the patients in the Johns Hopkins study were treated, Johns Hopkins doctors did not believe in early hormonal therapy (or other intervention, such as radiation) following recurrence. Their strategy was to generally wait until the patient developed symptoms of metastasis before using hormonal or other therapy. (I don't know that based on direct knowledge of course, but Dr. Charles Myers has stated exactly that, and he is a highly respected specialist in prostate cancer.) Today many doctors, probably including Johns Hopkins doctors, think that delaying intervention after recurrence is not wise, and they think that early intervention after recurrence is far superior, greatly increasing the chance for much longer survival. If that is true, then even higher percentages of Gleason 8 and higher patients would have survived to the fifteen year point.

Comments?

Jim

Last edited by IADT3since2000; 03-21-2008 at 02:11 PM. Reason: omitted letter d

 
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Old 02-07-2008, 03:04 AM   #2
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"confined to the prostate"?

I will be having my prostate removed soon. PSA3.02, Gleason 8, from psa 1.48 to 3.02 in 15 months: doubled in 15 months. bone /lymph scan negative. So, after removal, I'm guessing "confined to prostate" means no positive margins and no extensions?

 
Old 02-07-2008, 04:36 AM   #3
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Re: "confined to the prostate"?

Quote:
Originally Posted by richarda123 View Post
I will be having my prostate removed soon. PSA3.02, Gleason 8, from psa 1.48 to 3.02 in 15 months: doubled in 15 months. bone /lymph scan negative. So, after removal, I'm guessing "confined to prostate" means no positive margins and no extensions?
Just to add a few brief words of encouragement...

My experience, I had similar pre-op PSA velocity. I was actually a G7 (in spite of a G6 biopsy). Bone scan & CT scan negative. Before making my decision for a da Vinci robotic LRP, I was told, "All indications are that my cancer appeared to be confined to the prostate." Robotic surgery on 01/30/2007.

My post-op pathology (lab) report of the removed tissue verified the above. That report was released to me exactly one year ago today! Since then, I've seen my urologist three (3) times as follows...

Three PSA tests = <.01
Three DRE exams = uneventful

My final PSA/DRE will be in March 2008. If all is well, he will release me back to my family doctor for normal yearly PSA tests. I got pretty friendly with my uro. We are members of the same YMCA and we work out together. Neat guy!

Anyway, so far, so good!

Hope your experience is similar!
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robotic LRP; Jan2007

Last edited by able5; 02-07-2008 at 04:51 AM.

 
Old 02-07-2008, 04:47 AM   #4
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Re: "confined to the prostate"?

Quote:
Originally Posted by richarda123 View Post
I will be having my prostate removed soon. PSA3.02, Gleason 8, from psa 1.48 to 3.02 in 15 months: doubled in 15 months. bone /lymph scan negative. So, after removal, I'm guessing "confined to prostate" means no positive margins and no extensions?
Are you going to Chicago for surgery?
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Old 02-07-2008, 08:07 AM   #5
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Re: "confined to the prostate"?

Hi again Able5: I remember you pointing me in the direction of Chicago a couple weeks ago and I really thank you for that. I've learned there is not a lot of robotic experience in Wisconsin. My Dr. finished his internship in 06 and has 20 robotics. Milwaukee has someone with around 100. You had mentioned Dr. Shalhav and I have my initial conference mid Feb. with him. His receptionist says he has about 3000 robotics. I've been very impressed with their web page. Again, thank you very much for the Chicago info, it really was encouraging.

 
Old 02-07-2008, 09:57 AM   #6
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Re: "confined to the prostate"?

Quote:
Originally Posted by richarda123 View Post
Hi again Able5: I remember you pointing me in the direction of Chicago a couple weeks ago and I really thank you for that. I've learned there is not a lot of robotic experience in Wisconsin. My Dr. finished his internship in 06 and has 20 robotics. Milwaukee has someone with around 100. You had mentioned Dr. Shalhav and I have my initial conference mid Feb. with him. His receptionist says he has about 3000 robotics. I've been very impressed with their web page. Again, thank you very much for the Chicago info, it really was encouraging.
Good for Able: offering a fine suggestion that's being acted upon! This reinforces why some of us keep posting- even without a medical degree we do have experience/personal research to offer and encourage those of you out there reading silently to feel free to pose your own questions.

 
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Old 02-07-2008, 07:53 PM   #7
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Re: "confined to the prostate"?

Quote:
Originally Posted by richarda123 View Post
I will be having my prostate removed soon. PSA3.02, Gleason 8, from psa 1.48 to 3.02 in 15 months: doubled in 15 months. bone /lymph scan negative. So, after removal, I'm guessing "confined to prostate" means no positive margins and no extensions?
I don't think you previously mentioned the earlier PSA and it's date. The increase in 15 months is "just" 1.54. While that is a lot from one viewpoint, it is very good news from another: it's well under "greater than 2.0" in the year prior to diagnosis. I may have mentioned this before, but teams led by renowned prostate cancer radiation oncologist/researcher Dr. Anthony D'Amico, MD, demonstrated that a PSA increase in the year prior to diagnosis of more than 2.0 was an additional, independent indicator of higher risk for both RP and RT. By contrast, an increase of 2.0 or less indicated lower risk than you would otherwise estimate. You, of course, are well under 2.0, and though your Gleason 8 cancer cells are probably leaking less PSA than lower Gleason cells, that would likely apply to both PSA readings, therefore probably not affecting the trend. The same situation regarding a lower than average PSA leak would also apply to the GS 8-10 men in the D'Amico study.

I have a copy of the complete D'Amico paper, and it gives some data on GS 8-10 men. There were 47 of them in the study, including 32 men with a rise in PSA not exceeding 2.0 in the year before diagnosis, and 15 with a rise of more than 2. By the end of the study, 38 of the 47 were still alive, or 81%, with 9 deceased, or 19%; the average follow up for the 47 men was 4.8 years. But it appears that all 9 deaths were in the group with a rise of more than 2. This fact is not directly stated in the paper, but when you look at all the numbers, that's the way it looks. (I can explain if anyone is interested.) If true, that means that 100% survival after an RP for all the 32 Gleason 8-10 men with a rise in PSA that did not exceed 2.0!

(There's a detailed graph of deaths and survival for the 15 GS 8 patients who experienced a PSA rise of more than 2.0 in the year prior to diagnosis. About 72% were alive at the 7 year point, and about 42% were alive at the ten year point. It's obviously better to have a rise in PSA not over 2, but even if it is over 2, this study shows that such patients still have a pretty good shot at 10 year survival. Moreover, there have been substantial improvements in treatments, case assessment, monitoring, recurrence treatments, and overall support since the time that these men were treated (1989 through 2002).)

Here's a real technical point for anyone looking at these numbers very closely. If you are just interested in the broad picture, skip this. It might seem that the superior survival for the 32 men with a rise not exceeding 2.0 was partly because their followup after RP appeared to be shorter, judging from the fact that followup for all 47 GS 8 patients was an average of 4.8 years, but the detailed graph for the 15 man group covers a ten year span. While not stated, I'm positive the average followup for the 15 man group was well short of 10 years. The graph was made using a technique called Kaplan-Meier survival estimating, and it covers men who had survived for 10 years at the point the study was ended. It also covers men who had survived at the end of the study but whose RPs had been later, so that by the end of the study, though they were still alive, they had survived for less than 10 years. The technique has a way of covering both. The bottom line: followup for both the 32 man and 15 man groups was probably fairly close, at least close enough so that followup time would not explain the survival advantage of having a PSA rise that did not exceed 2.0.

Jim

 
Old 03-21-2008, 02:30 PM   #8
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Re: Gleason 8 (and higher) cancer: not good, but not always the end of the world

NEW STUDY FAVORS SUPPORTIVE RADIATION FOR HIGH-RISK RP PATIENTS

Results from an important clinical trial were recently reported for high-risk RP patients who were randomized to either radiation shortly after their surgery or no radiation after their surgery. Gleason 8 patients are usually considered high-risk patients. The trial was known as SWOG 8794. (SWOG stands for Southwest Oncology Group.)

Dr. Charles Myers, an eminent medical oncologist specializing in prostate cancer (and a veteran of his own challenging case of PC), wrote this in February about the trial results: "The results showed that adjuvant radiation therapy rather dramatically reduced the risk of subsequent metastatic disease.... There is a similar study done in Europe that confirms this dramatic advantage. I think this now defines what should be the standard of care. That is, if you have a high risk disease and elect surgery, you should have adjuvant radiation therapy. If you elect to delay treatment until disease recurrence becomes evident, you dramatically reduce your risk of survival."

It would be interesting to run a few examples of Gleason 8 cases through the Memorial Sloan Kettering formulas to see what difference the addition of radiation made in their outcome data. However, I'm not sure it's clear whether their RP patients getting supportive radiation were getting it shortly after surgery or not.

Jim

 
Old 03-21-2008, 05:42 PM   #9
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Re: Gleason 8 (and higher) cancer: not good, but not always the end of the world

Quote:
Originally Posted by IADT3since2000 View Post
NEW STUDY FAVORS SUPPORTIVE RADIATION FOR HIGH-RISK RP PATIENTS

Results from an important clinical trial were recently reported for high-risk RP patients who were randomized to either radiation shortly after their surgery or no radiation after their surgery. Gleason 8 patients are usually considered high-risk patients. The trial was known as SWOG 8794. (SWOG stands for Southwest Oncology Group.)

Dr. Charles Myers, an eminent medical oncologist specializing in prostate cancer (and a veteran of his own challenging case of PC), wrote this in February about the trial results: "The results showed that adjuvant radiation therapy rather dramatically reduced the risk of subsequent metastatic disease.... There is a similar study done in Europe that confirms this dramatic advantage. I think this now defines what should be the standard of care. That is, if you have a high risk disease and elect surgery, you should have adjuvant radiation therapy. If you elect to delay treatment until disease recurrence becomes evident, you dramatically reduce your risk of survival."

It would be interesting to run a few examples of Gleason 8 cases through the Memorial Sloan Kettering formulas to see what difference the addition of radiation made in their outcome data. However, I'm not sure it's clear whether their RP patients getting supportive radiation were getting it shortly after surgery or not.

Jim
Does this lead one to think that perhaps radiation instead of surgery can then be the preferred way to go? As I've said before, encountering failed surgery patients at Univ of Florida Proton Therapy Institute made me (and more importantly them) questioning why they didn't learn of the proton alternative before undergoing surgery.

 
Old 03-24-2008, 07:14 PM   #10
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Re: Gleason 8 (and higher) cancer: not good, but not always the end of the world

Quote:
Originally Posted by daff View Post
Does this lead one to think that perhaps radiation instead of surgery can then be the preferred way to go? As I've said before, encountering failed surgery patients at Univ of Florida Proton Therapy Institute made me (and more importantly them) questioning why they didn't learn of the proton alternative before undergoing surgery.
The kind of radiation used targeted the pelvic area to get cancer that was beyond the range of surgery. Can proton therapy target prostate cancer that is not within or very near the prostate? Even if it could not, it makes sense that a combination of proton beam and IMRT could be used to cover the whole region.

Dr. Dattoli's approach would be to use seeds and IMRT for the whole job, or maybe just IMRT, and one of those options would probably be the approach of other radiation doctors too except those using proton therapy. Depending on the case, many would probably add a course of hormonal blockade therapy. I'm going to add a post on a study about hormonal blockade as a booster for high risk cases treated with radiation. It deserves a separate post so it won't get lost.

It makes sense that you could also use radiation to back up cryo for high risk cases.

Jim

 
Old 03-26-2008, 03:05 PM   #11
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Re: Gleason 8 (and higher) cancer: not good, but not always the end of the world

Hormonal therapy as a booster to radiation for high-risk cases

I apologize for inadvertently including contact information in the previous post. I'll keep a close eye on that in the future.

Here is the interesting study I was trying to communicate. The Swedish Karolinska Institutet is known for its national studies of cancer therapies and outcomes, including prostate cancer. Prostate cancer is a substantial problem in Sweden, perhaps in part because of its Northern latitude and associated shortage of sunlight, probably leading to too little vitamin D. It's encouraging that their research showed solid favorable results for combining radiation and adjuvant hormonal therapy.

"Acta Oncol. 2004;43(4):316-81. A systematic overview of radiation therapy effects in prostate cancer. Nilsson S, Norlén BJ, Widmark A.

This is one of the few strong conclusions in the study. It supports the use of hormonal therapy to backup radiation for higher risk cases.
".... There is strong evidence that adjuvant endocrine treatment ["endocrine treatment" means hormonal therapy, and by calling it "adjuvant," it's likely the therapy came shortly after the radiation and was not done only when there was a recurrence] after curative radiotherapy results in improved local control, increased freedom from distant metastases, and increased disease-free survival in patients with loco-regionally advanced and/or high-risk disease...."

This is what the study was based on: "A systematic review of radiation therapy trials in prostate cancer has been performed according to principles adopted by the Swedish Council of Technology Assessment in Health Care (SBU). This synthesis of the literature is based on data from one meta-analysis, 30 randomized trials, many dealing with hormonal therapy, 55 prospective trials, and 210 retrospective studies. Totally the studies included 152,614 patients...."

 
Old 03-26-2008, 05:57 PM   #12
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Re: Gleason 8 (and higher) cancer: not good, but not always the end of the world

Johns Hopkins study on RP outcome for Gleason 8 to 10 patients; recommendation

Here's a fairly recent (2006) study from Johns Hopkins of outcomes for RP patients with biopsy Gleason scores in the 8 to 10 range. Excerpts from the background and conclusions sections of the abstract are included, and it's clear the team thought that more than just surgery was needed for these patients. Previous posts have covered research on some of the other options.

"Cancer. 2006 Sep 15;107(6):1265-72.

Clinical and pathologic outcome after radical prostatectomy for prostate cancer patients with a preoperative Gleason sum of 8 to 10.

Bastian PJ, Gonzalgo ML, Aronson WJ, Terris MK, Kane CJ, Amling CL, Presti JC Jr, Mangold LA, Humphreys E, Epstein JI, Partin AW, Freedland SJ.

BACKGROUND: Men with a biopsy Gleason sum of 8 to 10 are considered high-risk. The current study sought to identify whether there was a subset of men with high biopsy Gleason sums who would have a good pathologic and biochemical outcome with surgical monotherapy. ... CONCLUSIONS: The majority of men with a biopsy Gleason sum of >or=8, regardless of where the patient is treated, had unfavorable pathologic disease and experienced a biochemical progression after radical prostatectomy. Even among men with organ-confined disease and negative surgical margins or pathologic Gleason sum <8, at least half of the men experienced a PSA recurrence. Patients with biopsy Gleason sum 8 to 10 cancers are good candidates for multimodal therapy. Whereas multimodal therapy has often meant radiation plus hormonal therapy, newer possibilities for multimodal therapy exist such as surgery with neoadjuvant or adjuvant chemohormonal therapy or surgery with adjuvant radiation."

One option the conclusion does not mention is surgery plus immediate hormonal therapy. Dr. Horst Zincke of the Mayo Clinic, Rochester, Minn., has explored that approach for decades, with impressive success for surgery patients with lymph nodes that contain prostate cancer.

Jim

 
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