Your Thoughts on 2007 Harvard Study, Please

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Zen9
Regular Member


Date Joined Oct 2009
Total Posts : 314
   Posted 6/6/2010 11:28 AM (GMT -6)   
Comrades,

After looking at this forum last night before going to bed, and knowing that I have my two-year post-operation PSA test coming up soon, I did something that I know I shouldn't have done - a quick Internet search about the significance of length of time until biochemical recurrence. I found this 2007 Harvard Medical School piece:

http://www.harvardprostateknowledge.org/node/22

I went to bed more than a little unsettled. The biochemical recurrence rates seem high compared to the nomograms I have used over the past couple of years. I have my own thoughts about deficiencies in this report, but I would appreciate any thoughts you might have.

Thanks very much in advance.

Zen9
No family history of PC.  PSA reading in 2000 was around 3.0 .  Annual PSA readings gradually rose; no one said anything to me until my PSA reached 4.0 in September 2007, at which point my internist advised me to see a urologist.   
Urologist advised a repeat PSA reading in six months = 4.0 .  Diagnosed May 2008 at age 56 as a result of 12 core biopsy.  Biopsy report by Bostwick Laboratories = Gleason 3 + 3. 
Interviewed two urologists - the one who did the biopsy and another - the latter had the biopsy slides re-examined = Gleason 3 + 3. 
Then went to M. D. Anderson Cancer Center in Houston in July 2008 and met with a urologist and a radiologist.  Biopsy slides re-examined yet again, this time by MDA's internal pathology department = Gleason 3 + 4.   
Chose da Vinci surgery over proton beam therapy; surgery performed at M. D. Anderson Cancer Center on August 15, 2008.  Post-operative pathology report = four tumors, carcinoma contained in prostate, clean (negative) margins, lymph nodes clear, seminal vesicles clear.  Gleason = 4 + 3. 
Minor temporary incontinence; current extent of ED uncertain due to lack of sexual partner; refused treatments for ED as being pointless under the circumstances. 
PSA readings: 
November 2008 = <0.1 ["undetectable"]
June 2009 = <0.1   
December 2009 = <0.1
 


John T
Veteran Member


Date Joined Nov 2008
Total Posts : 4269
   Posted 6/6/2010 12:31 PM (GMT -6)   
Zen,

Seems a little high when compared to all of the other studies I have read. Low risk should have about a 10% chance of reoccurrance, intermediate risk about 30% and high risk 50% or greater. Overall rate of reoccurrance for all risks combined is about 30%.
JT

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.

JohnT


Galileo
Veteran Member


Date Joined Nov 2008
Total Posts : 697
   Posted 6/6/2010 12:32 PM (GMT -6)   
My thoughts are that the Harvard study is a little dated at this point. (BTW, so is Walsh's book on this particular topic, in my opinion) The study cites an important study, the one by Stephenson in 2004. That study was updated in 2007. Stephenson has found that subsets of men who were thought not to be candidates for salvage actually can do very well. The nomogram on the MSKCC website about salvage is based on the 2007 study and a correction that had to do with hormone therapy. At the time the Harvard piece was written, Stephenson's earlier article had just come out, and the important good news it carried are underweighted in the article, I think.

As far as the rate of biochemical recurrence after surgery, that sounds right in line with everything else I've read--up to about 30% of men will experience BCR at some point after surgery, but the data includes surgeries from quite a while ago. Walsh, in his 2007 book (p. 372) says: "At last, we have truly long-term results on a large number of men who have been followed for more than 20 years. In all of these patients, the probability of maintaining an undetectable PSA at five, ten, fifteen, and twenty years was 90 percent, 82 percent, 78 percent, and 71 percent, respectively." He goes on to note, however, that because of the longitudinal nature of the study, hundreds of men involved were diagnosed in the pre-PSA era, when cancer was more likely to be diagnosed at later stages. He says that a later study shows that "in men who underwent surgery between 1989 and 1992, it [the freedom from BCR rate] skyrocketed to 80 percent" from the 67 percent BCR-free who had surgery between 1982 and 1988. So yes, IMHO, 15-30% sounds about right, but for people like yourself, the BCR rate is probably pretty low comparatively speaking.

On a personal note, having had biochemical recurrence and undergoing salvage, men like me have a 38% chance of success six years out. Not the greatest of odds, but they beat the alternative had I chosen to not do salvage. If I had based my decision on studies earlier than those of Stephenson's, I might not have been so enthusiastic, since it's easy to find more simplistic predictions like "If your PSA is doubling faster than 10 months, you likely have metastatic disease and should not undergo salvage radiation" or "If your PSA rises within the first year", or even worse "salvage radiation should be performed only when the cancer is confirmed to still be local" etc. We now know that predicting the outcome of salvage radiation is more subtle, and often surprising. For example, Trock, Walsh, Partin, et al. recently found that salvage radiation seems to impart the greatest survival benefit precisely to the men who used to be thought beyond salvage--those whose doubling time was the fastest. (See: Trock BJ, Han M, Freedland SJ, Humphreys EB, DeWeese TL, Partin AW, Walsh PC. Prostate cancer-specific survival following salvage radiotherapy vs observation in men with biochemical recurrence after radical prostatectomy. JAMA. 2008 Jun 18;299(23):2760-9. PubMed PMID: 18560003.) Stephenson has found that a single high risk factor (Gleason 8 or higher, fast doubling time, short time to recurrence, etc) isn't all that important. Now when you start adding them together, it's a different story.

Zen9, looking at your stats in your signature, I would not be overly worried about all of this. Chances are, you won't have a recurrence, and if you do, there will be two questions: 1.) Will you otherwise live long enough for this to bother you? and 2.) Is the cancer likely localized? In the first question, if your PSA starts creeping back 20 years from now, maybe you won't have to anything at all. If you're still young enough to worry about it, salvage RT may offer you a second shot, and speaking for myself, SRT isn't anything to be afraid of.

Just my thoughts! Thanks for bringing this interesting topic up for discussion.
Galileo

Dx Feb 2006, PSA 9 @age 43
RRP Apr 2006 - Gleason 3+4, T2c, NX MX, pos margins
PSA 5/06 <0.1, 8/06 0.2, 12/06 0.6, 1/07 0.7.
Salvage radiation (IMRT) total dose 70.2 Gy, Jan-Mar 2007@ age 44
PSA 6/07 0.1, 9/07 and thereafter <0.1
http://pcabefore50.blogspot.com


Zen9
Regular Member


Date Joined Oct 2009
Total Posts : 314
   Posted 6/6/2010 1:55 PM (GMT -6)   
Thanks to you both.

I think it was reading that someone like me with a Gleason score of 4 + 3 (albeit negative margins, over a year post-op of undetectable PSA, etc.) had an 85% chance of biochemical recurrence within 5 years that caught me by surprise. I've already decided not to take any more treatment if my cancer returns, so these percentages have extra special significance for me!

Zen9
No family history of PC.  PSA reading in 2000 was around 3.0 .  Annual PSA readings gradually rose; no one said anything to me until my PSA reached 4.0 in September 2007, at which point my internist advised me to see a urologist.   
Urologist advised a repeat PSA reading in six months = 4.0 .  Diagnosed May 2008 at age 56 as a result of 12 core biopsy.  Biopsy report by Bostwick Laboratories = Gleason 3 + 3. 
Interviewed two urologists - the one who did the biopsy and another - the latter had the biopsy slides re-examined = Gleason 3 + 3. 
Then went to M. D. Anderson Cancer Center in Houston in July 2008 and met with a urologist and a radiologist.  Biopsy slides re-examined yet again, this time by MDA's internal pathology department = Gleason 3 + 4.   
Chose da Vinci surgery over proton beam therapy; surgery performed at M. D. Anderson Cancer Center on August 15, 2008.  Post-operative pathology report = four tumors, carcinoma contained in prostate, clean (negative) margins, lymph nodes clear, seminal vesicles clear.  Gleason = 4 + 3. 
Minor temporary incontinence; current extent of ED uncertain due to lack of sexual partner; refused treatments for ED as being pointless under the circumstances. 
PSA readings: 
November 2008 = <0.1 ["undetectable"]
June 2009 = <0.1   
December 2009 = <0.1
 


Purgatory
Elite Member


Date Joined Oct 2008
Total Posts : 25393
   Posted 6/6/2010 3:26 PM (GMT -6)   
Zen,

I see we are both the same age and both Gleason 7. As much as I dreaded going through radiation a second time in my life, and knowing that the long term odds of it helping were greatly reduced, the deciding factor for me was my age. If I had been 67 or 77 when I had recurrance, I don't think I would have done it. Right now, despite the complications, and the fact that my own radiation oncologist put the odds of the SRT working at 20-30% in my case, I still bit the bullet and did it. Part of me wishes still that I hadn't (my opinion on a bad day) but overall, felt it was my best and only hope of a cure.
Each person has to decide such things for himself, of course, and I respect any person's choice. If this SRT doesn't last or hold, I do not intend to go the HT route. That is my opinion today. Will it be the same in the future? Don't know till I am faced with it.

With you coming up on the 2 year mark still pulling zeros, definitely doesn't look like you are on the fast recurrance track, and I hope you stay that way.
That's the trouble with Gleason 7 cases, very unpredictable.

Still think you are doing pretty good.

David in SC
Age: 57, 56 dx, PSA: 7/07 5.8, 7/08 12.3, 9/08 14.5, 10/08 16.3
3rd Biopsy: 9/08 - 7/7 Positive, 40-90% Cancer, Gleason 4+3
Open RP: 11/08, Rht nerves saved, 4 days in hospt, on catheters for 63 days, 5th one out 1/09
Path Rpt: Gleason 3+4, pT2c, 42g, 20% cancer, 1 pos margin
Incontinence:  1 Month     ED:  Non issue at any point post surgery, no problem post SRT
Post Surgery  PSA: 2/09 .05,5/09 .1, 6/09 .11. 8/09 .16
Post SRT PSA: 1/10 .12, 4/8 .04, next one:  July
Latest: 7/9 met 2 rad. oncl, 7/9 cath #6 - blockage, 8/9 2nd corr surgery, 8/9 cath #7 out 38 days, 9/9 - met 3rd rad. oncl., mapped  9/9, 10/1 - 3rd corr. surgery - SP cath/hard dialation, 10/5 - 11/27 IMRT SRT 39 sess/72 gys ,cath #8 33 days, Cath #9 35 days, 12/7 - Cath #10 43 days, 1/19 - Corr Surgery #4,  Caths #11 and #12  same time, 2/8-Cath #11 out - 21 days, 3/2- Cath #12 out - 41 days, 3/2- Corr Surgery #5, 3/6 Cath #13 out - 4 days, Cath #14- 27 days, Cath #15 - 26 days, Cath #16 - 31 days, 5/24 put in Cath #17


Zen9
Regular Member


Date Joined Oct 2009
Total Posts : 314
   Posted 6/6/2010 3:40 PM (GMT -6)   
Thanks, and I likewise respect your choices, even if I sometimes would choose differently myself. Just feel so helpless, would love to be able to hand you a key that would release you from the hell you are in now, but feel so helpless.

I am in awe that you are about to start a new job when you are suffering the level of pain you are now.

I would love it if you would start a new thread and discuss a little philosophically how your feelings about pain have changed as a result of having PC. Others might have interesting thoughts also.

Zen9

rob2
Veteran Member


Date Joined Apr 2008
Total Posts : 1132
   Posted 6/6/2010 3:41 PM (GMT -6)   
Zen, I forgot the website but there was one that you could put in your stats and it would provide you the rate of recurrence percentage. I was gleason 8 and rate came back at 15% chance. I am at the 2 year mark and the PSA has been uncer .04 since surgery. By the way, why wouldn't you do any additional treatment?
 
Age 48 at diagnosis
occupation accountant
PSA increased from 2.6 to 3.5 in one year
biopsy march 2008 - cancer present gleason 7
Robotic Surgery May 9, 2008 - houston, tx
Pathology report -gleason 8, clear margins
22 month  PSA <.04
continent at 10 weeks (no pads!)
ED is still an issue


Zen9
Regular Member


Date Joined Oct 2009
Total Posts : 314
   Posted 6/6/2010 4:00 PM (GMT -6)   
Rob2,

Thanks, they are called "nomograms" and I have several well-known ones bookmarked. The fact that this Harvard article reached conclusions that seemed so out of line with these nomograms is what made me start this thread in the first place.

As to your second question about refusing radiation treatment - that's just my personal evaluation of the pros and cons. Just like Purgatory says he wouldn't choose to undergo hormone therapy (I wouldn't either). In fact, go all the way back and read Purgatory's personal story from the beginning and tell me that you would choose to undergo radiation therapy after biochemical recurrence after surgery!

I am not afraid of death; dying is a another matter. I have seen end stage cancer up close. Better to end it quickly, fade to black in a few seconds.

None of this is meant to be critical of anyone else's choices. Everyone is different, and I stand in awe of many people on this board. But I've never "run with the crowd." Inside, still a child of the '60's, I guess.

Zen9

Post Edited (Zen9) : 6/6/2010 3:39:28 PM (GMT-6)


compiler
Veteran Member


Date Joined Nov 2009
Total Posts : 7270
   Posted 6/6/2010 4:57 PM (GMT -6)   

Zen:

This is very weird. We have similar stats, except I was dx. in December '09.

I have a positive margin and extra caps. ext.

Yet, the nomograph says my chances of no bio reoccurence is:

91%-- 2 years

82% -- 5 years

78% -- 7 years

72% -- 10 years

 

Mel

 


63 years old . PSA-- 3/08--2.90; 8/09--4.01; 11/09--4.19 (Free PSA 24%),  after 45 days on cipro! DREs have always been normal. PCA-3 was about 75 (way above the 35 threshold). That led to:

Biopsy on 11/30/09. 5 out of 12 cores positive. Gleason 4+3. 2 cores were 3+3 (one 5% and the other 30%) on one side. On  other side:2 cores are 4+3 (5%)--1 core 3+4 (30%) no peri-neural invasion. prostate is 45 grams. Stage: T1C.  

Surgery with Dr. Menon at Ford Hospital, 1/26/10. He says all looked good. Spared nerves. Unfortunately: Pathology Report: G 4+3 (65%-35%). Cancer in 15% of gland. Lymph Nodes: Clear.  Perineural Invasion: yes. Seminal Vessical Involvement: No.  Extraprostatic Extension: yes.  Positive Margin: Yes-- focal-- 1 spot .5mm. Final Weight is 52.7 gms.  (Second opinion from Jon Epstein at Hopkins confirmed these results)

 Incontinence: joined that club-- definite leaks—1 pad/day. Night is dry, was  using 1 pad at night for security, but pretty much dispensed with that most nights. Update: no pads at night. No pads while at home, but still very uncomfortable. Use 1 pad for out-of-house activities. Suddenly got MUCH better on 3/10/10, almost overnight. Still some urgency but no pads about 90% of the time.  As of 3/12/10--completely continent! Uh...OH. As of about 3/16/10 problems with constant urgency although no pads needed--feels like an infection but none showing in urine.

Update: since late March all is well in that area. I would say 99.9% continent (a spurt here and there, maybe 5 spurts per week).

First post-op PSA on 3/10/10--DRUM ROLL: 0.01 Next PSA in mid-June.


Zen9
Regular Member


Date Joined Oct 2009
Total Posts : 314
   Posted 6/6/2010 5:23 PM (GMT -6)   
Compiler,

Yeah, that's exactly why I questioned the Harvard study. It seemed an outlier - big time! (I hope so, anyway ....)

Zen9

rob2
Veteran Member


Date Joined Apr 2008
Total Posts : 1132
   Posted 6/6/2010 5:47 PM (GMT -6)   
Zen, meant to wish you well on your test. As you may know, I had my second opinion at MDA but had my surgery at Methodist. I have used the nomogram at Sloan-Kettering.
 
Age 48 at diagnosis
occupation accountant
PSA increased from 2.6 to 3.5 in one year
biopsy march 2008 - cancer present gleason 7
Robotic Surgery May 9, 2008 - houston, tx
Pathology report -gleason 8, clear margins
22 month  PSA <.04
continent at 10 weeks (no pads!)
ED is still an issue


Zen9
Regular Member


Date Joined Oct 2009
Total Posts : 314
   Posted 6/7/2010 9:00 AM (GMT -6)   

Thanks, Rob2.  Good luck on your post-op journey.

I was all set to use Dr. Miles at Methodist when insurance problems arose and I went with Plan B = Dr. Davis at M. D. Anderson.  I thought Dr. Davis himself was very good - not a great communicator but a nice guy and an excellent surgeon - but I had a lot of problems with M.D. Anderson Hospital.

Zen9



SHU93
Regular Member


Date Joined Aug 2008
Total Posts : 328
   Posted 6/7/2010 10:09 AM (GMT -6)   
So what risk am I with a Gleason Score 6, psa lower then 10, but stage t2c?

What are my proable stats on reoccurrence?
Age Dx 37, 7/2008, First PSA : 4.17 5/2008
Second PSA After 2 weeks of antibiotics : 3.9 6/2008
DRE: Negative 5/2008, Biopsy: 6 out 12 Postive all on right side, Gleason 7 (3+4). Bone Scan/CAT Scan: Clear 7/2008
Cystoscope: Normal 7/2008, Prostate MRI: Normal 7/2008
Da Vinci Surgery 7/2008, PostOp: T2c (On Both sides), margins clear, seminal clear, nodes, clear. Gleason 6(3+3).
6 Post OP PSA's from 9/2008 to 6/2010: <0.1
 
 
 


ChrisR
Veteran Member


Date Joined Apr 2008
Total Posts : 831
   Posted 6/7/2010 10:44 AM (GMT -6)   
 
SHU93,
 
According to John Epstien at Johns Hopkins your chances of have a reccurence is 4/10th of 1%.  In other words G6 with no adverse pathologica features is cured 99.6% of the time.  At least at Johns Hopkins it is.  I believe J.H. over Harvard.  The Harvard study was done in 2007 and J.H. study was done in the fall of 2009.  Even the ones that did come back nobody developed systematic desease or died of PCa.  The J.H. study went as far out as 22 years.
Dx 42
Gleason 6 (tertiary score 0)
OPEN RP 10/08  Johns Hopkins
pT2 Organ confined Gleason 6
PSA Undetectable as of 10/15/09
Next PSA 10/15/2010


Zen9
Regular Member


Date Joined Oct 2009
Total Posts : 314
   Posted 6/7/2010 11:00 AM (GMT -6)   

Would you please post the link to the 2009 Johns Hopkins nomogram?

I have an earlier version bookmarked.

Thanks.

Zen9


ChrisR
Veteran Member


Date Joined Apr 2008
Total Posts : 831
   Posted 6/7/2010 1:28 PM (GMT -6)   
 
It was posted on the Prostate Cancer Info. Link site originally.
 
Here is a link to the article.
 
 
I guess it is all in who you want to believe.  30% from Harvard or .4% from Johns Hopkins.  For Gleason 6...I believe Johns Hopkins for obvious reasons.  It is also why I went there.  They had the best published stats. for Gleason 6.  Hope they aren't cookin' their books.   Who knows how Harvard arrived at their number.
 
 


Dx 42
Gleason 6 (tertiary score 0)
OPEN RP 10/08  Johns Hopkins
pT2 Organ confined Gleason 6
PSA Undetectable as of 10/15/09
Next PSA 10/15/2010


Old Sailor
Regular Member


Date Joined Aug 2009
Total Posts : 209
   Posted 6/7/2010 3:52 PM (GMT -6)   

 Zen, very interesting read.  Based on what I have read about PCa, I think very few men are truly "cured" of prostate cancer particularly any man with a primary pattern of 4 on the gleason scale.    Instead, I think we are "buying" time and the amount of time we "buy" is determined by the risk category we are in.  In my case with a high gleason and rising PSA after prostatectomy and now completion of IMRT, with hormone therapy looming as the last barrier if IMRT fails,  I feel like I have "bought" maybe 5 or 6 years.  I hate to be a pessimist but as they say, "it is what it is" and we have to make the best of the time we have left. It really grates on me when someone says "if your going to get cancer, prostate is the one to get."  Right!!!  Although slower to cause death than pancreatic, lung and brain cancer, ultimately, the ending is the same in this book, just a few more chapters added on.

The Old Sailor   


Dx 07/09 Age 67  -  28 core saturation biopsy w/5 positive  (2 gleason 8, 2 gleason 7, 1 gleason 6)
RRP 8/13/09 Mayo Clinic Jacksonville
Path report upgraded gleason to 4+5=9
Negative margins/extraprostatic extension/seminal vessicles/ lymph nodes but perineural invasion present.
Two month post surgery PSA 0.022
Five month post surgery PSA  0.081
Seven month post surgery PSA 0.190
Eight month post surgery PSA 0.217
Started 38 sessions IMRT at Mayo Jacksonville on 4/12/10,  completed 6/4/10.  Few side effects except urinary urgency and  frequency during the day and some rectal discomfort near the end of therapy. 

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