BCR VERSUS OVERALL SURVIVAL

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Hubby's Advocate
New Member


Date Joined Feb 2010
Total Posts : 5
   Posted 2/13/2010 12:10 PM (GMT -6)   
First let me say this is a great site and thanks to all the members who take the time to answer with information and web sites.
 
I see alot about Salvage radiation and Adjuvant Radiation information regarding signifacantly better Biochemical recurrence data but have not seen where the overall survival and distant metastisis is significantly different statistically with versus without treatment.  Is anybody else finding this or does anybody know that overall survival is statistically better with treatement.
 
Age 62
Pre Surgery psa 4.6.  Biopsy gleason 4+3=7
Divinchi January 4th.
Pathology from surgery
Gleason 4+3=7
Present in right and left lobes and involving approximately 40% of prostate tissue.
Tumor involves inked margin at base.
Extraprostatic extension  none identified
Seminal vesicles  Involved
Perineural invasion  Yes
Lymphatic/vascular invaision Yes
Lymph nodes  Negative
Tumor t3b
Some sites say it is t3c with seminal invasion.
First psa 0 after surgery January 27th. 
 

Aprilsunny
New Member


Date Joined Jan 2010
Total Posts : 15
   Posted 2/13/2010 1:36 PM (GMT -6)   
Hi, Hubby's Advocate,

(Sorry, long again.)

Another couple of articles that might help answer your question:

Is There a Standard of Care for Pathologic Stage T3 Prostate Cancer? - an analysis from 2009 of three long-term trials.

"The updated results of the SWOG trial with median follow-up of 12.6 years found a significant improvement in metastasis-free survival (HR, 0.71; 95% CI, 0.54 to 0.94; P = .016) and overall survival (HR, 0.72; 95% CI, 0.55 to 0.96; P = .023) with radiotherapy"

and
Prostate Cancer–Specific Survival Following Salvage Radiotherapy vs Observation in Men With Biochemical Recurrence After Radical Prostatectomy - a small retrospective study whose authors include Partin and Walsh, from 2008.

"Salvage radiotherapy alone was associated with a significant 3-fold increase in prostate cancer–specific survival relative to those who received no salvage treatment (hazard ratio [HR], 0.32 [95% confidence interval {CI}, 0.19-0.54]; P<.001). Addition of hormonal therapy to salvage radiotherapy was not associated with any additional increase in prostate cancer–specific survival (HR, 0.34 [95% CI, 0.17-0.69]; P = .003). The increase in prostate cancer–specific survival associated with salvage radiotherapy was limited to men with a prostate-specific antigen doubling time of less than 6 months and remained after adjustment for pathological stage and other established prognostic factors. Salvage radiotherapy initiated more than 2 years after recurrence provided no significant increase in prostate cancer–specific survival. Men whose prostate-specific antigen level never became undetectable after salvage radiotherapy did not experience a significant increase in prostate cancer–specific survival. Salvage radiotherapy also was associated with a significant increase in overall survival.'

The latest large clinical trial, RADICALS, which compares adjuvant or salvage radiation therapy with/without hormonal therapy, began recruiting in 2007, I believe.

Hope this helps a little,

Best of luck, AS
Brief History (Husband)

Age - 60

4th of 5 brothers. Brother 3 died at 65 of PCa, brother 2 is five-year survivor of PCa, (brother 1 died at 61 of heart attack). So far brother 5 is okay.

PSA - October 2009 - 6.4
Biopsy - November 17, 2009 - Gleason 4+3=7 DRE Normal Stage T1C
open RP - January 14, 2010


Tony Crispino
Veteran Member


Date Joined Dec 2006
Total Posts : 8128
   Posted 2/13/2010 2:21 PM (GMT -6)   
Hi Hubby's Advocate.

There is significant data available that show definable differences in biochemical relapse between salvage radiation versus adjuvant radiation, when combined with a two year stint on androgen deprivation therapy. I went with this logic in my case. Overall survival is still undefined, but as time is moving along I believe that it will be more clear. Much has changed since the Walsh/Partin study that has been noted by April above. Studies by Stanford and Harvard have shown significant improvement in relapse statistics, which most oncologists agree will result in improvement in overall survival.

Note about T3B and T3C. T3C is no longer a pathological stage in prostate cancer. Doctors and pathologists using it are using out of date American Joint Committee on Cancer tables. In the AJCC1997 staging manual there was a T3C. Starting with AJCC2002, the manual combines what was T3A and T3B to T3A. T3B is now the same as what T3C was in 1997, which is seminal vesicle invasion.

Here are my statistics:

Dx at age 44
PSA at 19.8; Gleason 3+4=7
4 of 8 cores positive up to 90%

Da Vinci surgery on Febryary 16, 2007
pT3b, N0, Mx; Gleason 4+3=7
Positive Margin, Extra-prostatic Extension, Postive seminal vesicles

PSA history:
October 3, 2006 19.8
October 10, 2006 18.9
November 27, 2006 13.9
Surgery February 16, 2007
February 28, 2007 0.9
March 12, 2007 0.1
March 23, 2007 <0.1
May 16, 2007 <0.1 ; Begin adjuvant hormonal therapy and IMRT radiation.
July 18, 2007 <0.1
September 19, 2007 <0.1
January 29, 2008 <0.1
May 9, 2008 <0.1
September 17, 2008 <0.1
January 13, 2009 <0.1
May 11, 2009 <0.1 T=50 ; Adjuvant hormonal therapy stopped in September 2009
October 7, 2009 <0.1 T=21 PAP=0.3
January 4, 2010 <0.1 T=128 PAP=0.4

Stay Positive is my motto...

Tony
Prostate Cancer Forum Co-Moderator


goodlife
Veteran Member


Date Joined May 2009
Total Posts : 2691
   Posted 2/13/2010 3:00 PM (GMT -6)   
Much of PC treatment is a game of statistical odds. While it is true that SRT may only give 30 out of 100 men no BCR after 10 years, if you are one of those 30 men, you feel much better.

I thnk the other problem is tracking actual results. Many of our quoted statistics come from studies of X number of men, in mulitple studies. Since we don't clearly track each man who has had PC, and define their cause of death, some of these statistical numbers may or may be true or applicalble to me.

I have seen statements made that state that there is no significant improvement in mortality rates for certain types of teratments, however, even an insignificant increase could be my life.

I have watched these numbers as well, and have held off on adjuvant radiation, which may statistically give me better BCR odds, they don't factor in quality of life issues which may occur. If and when my PSA's start to rise ( and as a Gleason 9 I will nit be totally surprised ), then I will consider SRT. If it can give me 5 more good years, then I may take it, even tho I may die of PC anyway.

All of these numbers are statistical, and do not guarantee me anything. Just like heads or tails is a 50/50 thing, doesn't mean it can't come up tails 10 times in a row, or land on its edge.

Good luck in your journeys. Enjoy life today.
Goodlife
 
Age 58, PSA 4.47 Biopsy - 2/12 cores , Gleason 4 + 5 = 9
Da Vinci, Cleveland Clinic  4/14/09   Nerves spared, but carved up a little.
0/23 lymph nodes involved  pT3a NO MX
Catheter and 2 stints in ureters for 2 weeks .
Neg Margins, bladder neck negative
Living the Good Life, cancer free  6 week PSA  <.03
3 month PSA <.01 (different lab)
5 month PSA <.03 (undetectable)
6 Month PSA <.01
1 pad a day, no progress on ED.  Trimix injection
No pads, 1/1/10,  9 month PSA < .01


bemis
Regular Member


Date Joined Feb 2010
Total Posts : 38
   Posted 2/13/2010 6:18 PM (GMT -6)   
has anyone seen data on how specific radiation delivery and amt[Gcy] affects outcome? DICK
age 55 /psa 10-09 5.4/biopsy 11-09 Gleson 3+3=6 3+4=7/ Radical prostateectomy 1/22/10/pathology positive margins and extraprostatic extension pY3a


Purgatory
Elite Member


Date Joined Oct 2008
Total Posts : 25364
   Posted 2/13/2010 7:41 PM (GMT -6)   
With IMRT, they can put more radiation into a very narrow specific area. The radiation oncologists I spoke with in person all wanted to do a min of 70 gys for my salvage. In the end, I took 72 gys spread over 39 treatments.
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
Post Surgery  PSA: 2/09 .05,5/09 .1, 6/09 .11. 8/09 .16
Post SRT PSA: 1/10 .12
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 in at the same time, 2/8-Cath #11 out - 21 days


Geebra
Regular Member


Date Joined May 2009
Total Posts : 476
   Posted 2/14/2010 1:51 AM (GMT -6)   
Tony,

I am a bit confused. You are saying (and so do my Onc and Rad docs) that there is a benefit to a combined SRT and HT. Yet the article that Aprilsunny provided (the 2008 retrospective study by Partin et al) says there was no benefit. Am I misinterpreting something or is it the difference of opinion between different studies?

Greg
Father died from poorly differentiated PCa @ 78 - normal PSA and DRE
5 biopsies over 4 years negative while PSA going from 3.8 to 28
Dx Nov 2007, age 46, PSA 29, Gleason 4+4=8
Decided to participate in clinical trial at Duke - 6 rounds of chemo (Taxotere + Avastin)
PSA prior to treatment 1/8/2008 is 33.90, bounced on 1/31/2008 to 38.20, and down at the end of the treatment (4/24/2008) to 20.60
RRP at Duke (Dr. Moul) on 6/16/2008, Gleason downgraded 4+3=7, T3a N0MX, focal extraprostatic extension, two small positive margins
PSA undetectable for 8 months, then 2/6/2009 0.10, 4/26/2009 0.17, 5/22/2009 0.20, 6/11/2009 0.27
ADT (ongoing, duration TBD): Lupron started 6/22/2009
Salvage IMRT to prostate bed and pelvis - 72gy over 40 treatments finished 10/21/2009
PSA 6/25/2009 0.1, T=516, 7/23/2009 <0.05, T<10, 10/21/2009 <0.05, T<10


Tony Crispino
Veteran Member


Date Joined Dec 2006
Total Posts : 8128
   Posted 2/14/2010 1:16 PM (GMT -6)   
Greg,
I am not certain that the above articles argue the point. Partin and Walsh have always been critical of introducing ART, but even they have softened their stance. For example the one article above offers these two paragraphs:

"The question of whether adjuvant radiotherapy should now be the standard of care for these patients remains. The answer is elusive for two reasons. First, the final results of the SWOG trial have just been reported but similar results of the EORTC trial are pending. The updated results of the SWOG trial with median follow-up of 12.6 years found a significant improvement in metastasis-free survival (HR, 0.71; 95% CI, 0.54 to 0.94; P = .016) and overall survival (HR, 0.72; 95% CI, 0.55 to 0.96; P = .023) with radiotherapy.5 We look forward to the results of longer-term follow-up of the EORTC study for these end points; meanwhile, the results of the SWOG trial are compelling.

The second reason why adjuvant radiation may not yet be the standard of care is that some experts feel that salvage radiotherapy may be equivalent. Salvage radiotherapy refers to radiation administered at the time a measurable PSA is detected. In the past few decades, the threshold of detection for PSA and the time threshold at which radiotherapy is recommended have changed. A decade or so ago, an undetectable PSA might have been < 0.4 ng/mL; today, with an ultrasensitive assay, it may be < 0.01 ng/mL. Likewise, a decade ago, radiotherapy was initiated before PSA level reached 1.5 ng/mL; now, often any level > 0.01 ng/mL may prompt a recommendation of radiotherapy."


Both paragraphs are off pace with Walsh's original book. In that book Walsh states there was no proof that overall survival improves with adjuvant therapy. But in his second edition, he states a different stance. He states that earlier therapy after relapse is showing improvement in overall survival. I can't help but believe that his second statement supports proponents of adjuvant radiation. That's as early as you can get. And yet there Walsh is in support of the article. But delivery of radiation has improved greatly and thus SE's have been reduced. Back in the day of a wide delivery of EBRT we saw many side effects that hampered quality of life. But today we can deliver higher gray with precision. Most who under go RT feel mostly a bit of fatigue, but otherwise tolerate the treatment well. And the stats have also been changed by including local lymph nodes in the adjuvant protocol, thus studies by Harvard and Stanford are leading the way for adjuvant therapies.

I believe the first paragraph is most accurate in controlling PSA, but I cannot completely argue a point about SRT and ART being close in numbers of overall survival. That's because the ART studies are at year 8 as opposed to SRT which has a longer study history. But that falls in line with my complaint that most 10-12 year studies are hampered by being too short, and having many study subjects die of age related disease other than PCa. I have made the point before, and I'll restate it again ~ We need studies of 15-20 years in younger age groups to properly evaluate performance of prostate cancer treatments. Until we have them, the confusion is understandable.

Interestingly, there is no argument the use of adjuvant therapy controls PSA and extends life of stage 4 post RP patients. I am absolutely certain it will eventually be proven in stage 3 men as well. At least I'm banking on it. The controversy for our stage is still there, but as we are gathering data, ART is looking better all the time...

Tony
Prostate Cancer Forum Co-Moderator

Post Edited (TC-LasVegas) : 2/14/2010 12:19:53 PM (GMT-7)


Galileo
Veteran Member


Date Joined Nov 2008
Total Posts : 696
   Posted 2/14/2010 1:43 PM (GMT -6)   
Hubby's Advocate:

I would just like to second what Aprilsunny wrote. I read a lot about this subject, having quite a bit at stake being a youngish patient (47 now) who has gone through salvage radiation.

You wrote:

"I see a lot about Salvage radiation and Adjuvant Radiation information regarding signifcantly better Biochemical recurrence data but have not seen where the overall survival and distant metastasis is significantly different statistically with versus without treatment. Is anybody else finding this or does anybody know that overall survival is statistically better with treatment?"

As to that specific question, the most relevant information I've seen is the article "Prostate Cancer–Specific Survival Following Salvage Radiotherapy vs Observation in Men With Biochemical Recurrence After Radical Prostatectomy" available in full text, for free at: http://jama.ama-assn.org/cgi/content/full/299/23/276
The lead author was Trock of Johns Hopkins Brady Institute and the co-authors, as Aprilsunny pointed out, are an impressive list: Han, Freedland, Humphreys, DeWeese, Partin, and Walsh.

Their analysis indicates that it is men with fast doubling times who appear to benefit the most, in terms of survival, from SRT. (Which, by the way was good news to me, since my PSADT was pretty fast, less than 90 days).

Dr. Catalona wrote about this study, and others, in one of his excellent newsletter articles, "To Do or Not to Do: Radiation After a Radical Prostatectomy" http://www.drcatalona.com/quest/quest_winter08_2.htm . An excerpt from Dr. Catalona:

"Possibly, the men with slower doubling times have less aggressive cancers with less need for salvage radiation. But it is also possible, and even likely, that with longer follow-up, men with slower PSA doubling times will be shown to receive a survival advantage from SRT as well.

In their article, researchers said, 'This study provides provocative evidence that even men with adverse prognostic features such as rapid PSA doubling time or high Gleason score may benefit from salvage radiotherapy'.

Before this study, the prevailing theory was that recurrence was evidence the cancer had metastasized in some other place or places in the body. This finding, they said, 'If true, has somewhat surprising implications for the prevalence of local recurrence as a source of PSA relapse'.

Additional findings suggested that men for whom salvage radiotherapy is most beneficial are those with a PSA doubling time of less than 6 months, who also undergo treatment within 2 years of an increase in PSA level and before the PSA reaches 2." (End quote).

So to me, things look promising in terms of actual survival, but the answer is not clear yet. One sobering fact is that so far, in the long run, according to Catalona, Andrew Stephenson, and others, more men have BCR than not after salvage radiation. At the 10 year mark, only 25-35% of men are still free from PSA progression following salvage. The percentage starts out much higher--about 3/4 of men are responders to SRT, but that drops to around 50% at 5 years (hence the "50/50" statement so often used about SRT) and then it continues to drop after that. Hopefully the stats will start to show better results, as time goes by, due to better radiation techniques. Time will tell.

I've put together a brief guide that encapsulates what I have read about salvage radiation. It's here: http://knol.google.com/k/salvage-radiation-for-prostate-cancer

Best wishes.
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

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