Immediate vs Salvage Radiation After RP

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julios
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Date Joined Jun 2010
Total Posts : 38
   Posted 11/9/2010 9:14 AM (GMT -6)   

Here's new research from UroToday saying your chances are better with having radiation therapy immediately (adjuvant) as opposed to waiting for your PSA to come back up. Note: "immediate" means after you have healed from RP; 2 or 3 months.

UroToday

A multi-institutional analysis comparing adjuvant and salvage radiation therapy for high-risk prostate cancer patients with undetectable PSA after prostatectomy - Abstract

Monday, 08 November 2010
Department of Radiotherapy and Oncology, University Hospitals Leuven, Leuven Cancer Institute, Leuven, Belgium.

In men with adverse pathology at the time of radical prostatectomy (RP), the most appropriate timing to administer radiotherapy (RT) remains a subject for debate. To determine whether salvage radiotherapy (SRT) upon early prostate-specific antigen (PSA) relapse is equivalent to immediate adjuvant radiotherapy (ART) post RP.

130 patients receiving ART and 89 receiving SRT were identified. All had an undetectable PSA after RP. Homogeneous subgroups were built based on the status (±) of lymphatic invasion (LVI) and surgical margins (SM), to allow a comparison of ART and SRT. Biochemical disease-free survival (bDFS) was calculated from the date of surgery and from the end of RT. The multivariate analysis was performed using the Cox Proportional hazard model.

In the SM-/LVI- and SM+/LVI- groups, SRT was a significant predictor of a decreased bDFS from the date of surgery, while in the SM+/LVI+ group, there was a trend towards significance. From the end of RT, SRT was also a significant predictor of a decreased bDFS in three patient groups: SM-/LVI-, SM+/LVI- and SM+/LVI+. Gleason score >7 showed to be another factor on multivariate analysis associated with decreased bDFS in the SM-/LVI- group, from the date of surgery and end of RT. Preoperative PSA was a significant predictor in the SM-/LVI- group from the date of RP only.

Immediate ART post RP for patients with high risk features in the prostatectomy specimen significantly reduces bDFS after RP compared with early SRT upon PSA relapse.

Written by:
Budiharto T, Perneel C, Haustermans K, Junius S, Tombal B, Scalliet P, Renard L, Lerut E, Vekemans K, Joniau S, Poppel HV.   Are you the author?

Reference: Radiother Oncol. 2010 Oct 13. [Epub ahead of print]
doi: 10.1016/j.radonc.2010.07.008

PubMed Abstract
PMID: 20950879

UroToday.com Prostate Cancer Section




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Age 52

At Diagnosis of PCa, had Gleason 9 and normal PSA

Radical Prostatectomy on July 7th, 2010 by Dr. Fagin using daVinci

25% to 50% nerves spared on left, 100% spared on right.

Continent from day one.

Pathology showed postive margins and extension beyond gland, including seminal vesicals and lymph nodes. Stage upgraded to T3b.

Casey59
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Date Joined Sep 2009
Total Posts : 3172
   Posted 11/9/2010 9:51 AM (GMT -6)   
julios said...

Note: "immediate" means after you have healed from RP; 2 or 3 months.

julios, thanks.  I also saw this report, but I did not see any reference to the "Note" you added, above.
 
Can you please clarify where this came from?
 
 
Also, I know that the abstract is supposed to be brief, but I was disappointed that it did not at least provide a balanced view by adding a mention of the overtreatment risk which occurs when men who might not otherwise have PSA recurrence are needlessly blasted by radiation, suffering unnecessary consequences...although (on the other hand) the report did focus on the benefit to high risk cases (Gleason of 8 or higher, PSMs, and LVI), which are cases in which surgery alone are less likely to be 100% curative. 

English Alf
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Date Joined Oct 2009
Total Posts : 2215
   Posted 11/9/2010 10:19 AM (GMT -6)   
Gleason score post op pathology all relevant.
Also need to think about quality of life issues, age of patient, side effects. and don't forget to treat the patient not just the cancer.

I will have a look for this study (As it's from Belgium the original may be in French or Dutch, but that should not present a problem for me.)

(My own PSA rose so soon after RP anyway that I never really had a chance to wait and see what might happen, so my SRT less than a year after surgery almost made it feel like it was ART)

Alf

edited addition: I think this is the article:
www.thegreenjournal.com/article/S0167-8140(10)00397-X/fulltext
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
Tired
BMs weird
14 Sep 10 PSA <0.1
Erections OK

Post Edited (English Alf) : 11/9/2010 9:37:26 AM (GMT-7)


julios
Regular Member


Date Joined Jun 2010
Total Posts : 38
   Posted 11/9/2010 11:12 AM (GMT -6)   
Dear Casey59,

The 2 or 3 months healing time is simply what both my urologist and radiation oncologist wanted when planning my radiation. They say if you radiate before full healing, it delays and makes healing more complicated. I have read research reports that document that.

Keep in mind that healing for ED and continence is essentially ended for most men at the time radiation begins, according to my docs and research I've read. I agree with Alf; other factors such as age need to be considered. But as I understand, it is the rare exception that PCa doesn't eventually return. The research I shared suggests adjuvant RT helps delay the return, if not prevent it.
Age 52

At Diagnosis of PCa, had Gleason 9 and normal PSA

Radical Prostatectomy on July 7th, 2010 by Dr. Fagin using daVinci

25% to 50% nerves spared on left, 100% spared on right.

Continent from day one.

Pathology showed postive margins and extension beyond gland, including seminal vesicals and lymph nodes. Stage upgraded to T3b.

Tony Crispino
Veteran Member


Date Joined Dec 2006
Total Posts : 8128
   Posted 11/9/2010 11:26 AM (GMT -6)   
Julios,
As my doctors have said ~ You are always at your best prior to starting any therapy.

Many centers show the same results with adjuvant radiation versus salvage radiation after prostatectomy. Here are a few that I have:

Mayo Clinic:
www.ncbi.nlm.nih.gov/pubmed/10737490

Baylor University Article:
www.medicalnewstoday.com/articles/43871.php

UCSF Article (Carroll):
esciencenews.com/articles/2010/08/06/surgery.better.radiation.hormone.treatments.some.prostate.cancer.study.shows

Stanford University (WPRT vs. PORT in high risk cases)
www.ncbi.nlm.nih.gov/pubmed/17459606?dopt=Abstract&otool=stanford

I don't think there is any doubt that biochemical failure is delayed by adjuvant radiation. We have even seen prostate cancer specific survival improve in the 5-10 year studies but we do need much more data on it. I chose adjuvant therapies as I already had the data for salvage radiation and HT. I wasn't too thrilled by what I read about salvage radiation being only 44 at the time. It made venturing out beyond to what data we don't have in regards to adjuvant therapies more comprehensible.

Tony
Disease:
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

Treatments:
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.

Status:
"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

Blog : www.caringbridge.org/visit/tonycrispino

Casey59
Veteran Member


Date Joined Sep 2009
Total Posts : 3172
   Posted 11/9/2010 11:35 AM (GMT -6)   
julios, thank you for your reply, and clarification that the "2-3 months" was your medical team's input and not part of the study.  There remains much debate on when to administer ART/SRT for the more medium risk cases; high risk cases like yours seem to be in higher agreement.
 
I would also agree with Alf that the additional factors/considerations he and you commented on are also important considerations.  Each case is unique and different.  I like how Alf said it (worth repeating):  "treat the patient not just the cancer."
 
Good luck in your journey...
 
Do you mind me asking a few questions about your case, for my own interest about learning more about the natural history?  A Gleason score of 9 with normal PSA is indicative of a uniquely aggressive case.  If you don't mind sharing this info, do you have any family history of PC?  Was your DRE abnormal?  What age was your first PSA & DRE?  Thanks in advance.

julios
Regular Member


Date Joined Jun 2010
Total Posts : 38
   Posted 11/9/2010 12:30 PM (GMT -6)   
Casey, I'm happy to share. There's a lot of cancer history in my family, but no prostate cancer, at least within three generations. My first PSA and DRE was at age 46. My family practise Dr. noted the left globe was slightly larger than the right. The next was at 49; same doc found left side much larger and abnormal and referred me to a uro. The uro did DRE, observed the same, but concluded it was simply the left seminal vesicle causing the abnormal feeling. No follow-up suggested. Next one was by original doc at age 52, who was quite alarmed when he felt it to be even bigger. Same uro felt it and immediately said most likely cancer. He did a biopsy only then, and confirmed it. So I probably had it for more than 6 years before diagnosis. PSA was normal the entire time (1.7 or so).
Age 52

At Diagnosis of PCa, had Gleason 9 and normal PSA

Radical Prostatectomy on July 7th, 2010 by Dr. Fagin using daVinci

25% to 50% nerves spared on left, 100% spared on right.

Continent from day one.

Pathology showed postive margins and extension beyond gland, including seminal vesicals and lymph nodes. Stage upgraded to T3b.

Purgatory
Elite Member


Date Joined Oct 2008
Total Posts : 25380
   Posted 11/9/2010 12:38 PM (GMT -6)   
julios,

good piece, but unfortunately, there are plenty of radiation and medical oncologists that strongly disagree with those findings. The trend I have seen in the past couple of years, is a move away from adjunct to SRT, except in very high risk cases, i.e. Gleason 8 and above. Since radiation as a secondary treatment to a failed surgery has a fairly low per cent of success on a good day, a person would sure want to make sure that the need and timing for it was justified, and not just shooting the patients last curative hope into the air. Like all things PC, nothing is easy or consistent, not even among the experts.

david
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 Not taking it
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 9/23/10

F8
Veteran Member


Date Joined Feb 2010
Total Posts : 3804
   Posted 11/9/2010 12:52 PM (GMT -6)   
>>and not just shooting the patients last curative hope into the air<<
 
i guess i don't understand this.  you'll either need RT or you won't.  the danger is "overtreatment", not wasting a curative bullet.  in my case i opted for combination treatment because there was a 60% chance that my PC was out of the capsule. 
 
ed
age: 55
PSA on 12/09: 6.8
no symptoms, no prostate enlargement
12/12 cores positive....gleason 3+4 = 7
HT, BT and IGRT
received 3rd and last lupron shot 9/14/10

English Alf
Veteran Member


Date Joined Oct 2009
Total Posts : 2215
   Posted 11/9/2010 1:02 PM (GMT -6)   
The full conclusions are:


The timing of postoperative RT remains controversial, because randomized trials to determine the incremental benefit of ART compared with early SRT given for an early PSA increase above the lower detection limit of modern PSA tests have not been performed.
In the absence of randomised data, this multi-institutional, retrospective comparison of ART compared with early SRT demonstrates a significant improvement in bDFS with immediate postoperative treatment for patients with high risk features in the RP specimen over SRT.
The incidence of both late grade 3 genitourinary and gastrointestinal toxicity following postoperative RT administered with modern RT techniques is low and acceptable, but continuous efforts have to be made in order to improve the therapeutic index.


So it's basically for high risk people where there is most chance of benefit. and note the word controversial in the first sentence, also that they also reckon the urinary and bowel side-effects are acceptable.

(And this study was also only for about 220 people)

So not that much of a study to draw too many conclusions from just yet.

Alf

Post Edited (English Alf) : 11/10/2010 1:55:38 AM (GMT-7)


Casey59
Veteran Member


Date Joined Sep 2009
Total Posts : 3172
   Posted 11/9/2010 1:37 PM (GMT -6)   

julios, thanks for sharing your history.  I don't have references at my fingertips, and of course the aggressive/indolent PCs are not thoroughly understood yet, but I recall reading retrospective info about low PSA/high Gleason combinations being infrequent, yet higher frequency among younger guys (like you) than older guys.  This is possibly counter-intuitive...

I recall from a post you made last month (a reply in a Piano thread) that your 2-month & 3-month post-RP PSAs were high right out of the gate, and you are now 4-months post-RP.  What are your RT and/or HT plans?  [I apologize if you have already discussed them in another thread.]

 



Purgatory
Elite Member


Date Joined Oct 2008
Total Posts : 25380
   Posted 11/9/2010 4:53 PM (GMT -6)   
F8/Ed - what I meant, perhaps wasn't clear, its always an educated gamble if using radiation as a secondary treatment is going to be effective. It all depends if the remaining cancer is still local to the prostate bed, or if it has long escaped. If it was all local, then adjunct or SRT could very well help, and possibly eliminate the remaining cancer. Unfortunately, there's no 100% way of knowing that.

Thats''s why there are plenty of radiation oncologists and medical oncologists that insist on waiting to see if there is any evidence of BCR before taking the secondary step.

Using my own case as an example. I had one small positive margin, full BCR within 9 months of surgery, and very volatile PSA velocity prior to surgery, my radiation oncologist only gave me a 20-25% chance of my SRT being sucessful. Not very good odds at all, but at least a chance, and certainly my last curative chance to stop the remaining PC. In my case, the jury is still out as if its going to work. The PSA velocity issue really works against me in the long term. But time will tell.

It's intersesting to me, that even among our group here at HW, which is just a small sample of the general PC population, that we have men that are Stage III, with Gleason 8 or above, they are doing better so far, then men, such as myself, that are Stage II with Gleason 7's.

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 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 Not taking it
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 9/23/10

AJ 47 (Maryland)
Regular Member


Date Joined Aug 2010
Total Posts : 64
   Posted 11/9/2010 6:22 PM (GMT -6)   
Add this article to the list of studies indicating favorable statistics from preemptive ART from The Journal Urology (2009) (sorry I can't find a full text link at this time):

Adjuvant Radiotherapy for Pathological T3N0M0 Prostate Cancer
Significantly Reduces Risk of Metastases and Improves Survival:
Long-Term Followup of a Randomized Clinical Trial
Ian M. Thompson,*,† Catherine M. Tangen, Jorge Paradelo, M. Scott Lucia,
Gary Miller,‡ Dean Troyer, Edward Messing, Jeffrey Forman, Joseph Chin,
Gregory Swanson, Edith Canby-Hagino and E. David Crawford
From the University of Texas Health Science Center at San Antonio (IMT, DT, GS) and Wilford Hall Medical Center (ECH), San Antonio, Texas, The Fred Hutchinson Cancer Research Center, Seattle, Washington (CMT), The Kansas City Community Clinical Oncology Program, Kansas City, Missouri (JP), The University of Colorado Health Science Center, Denver, Colorado (MSL, GM, EDC), The James P. Wilmot Cancer Center, University of Rochester School of Medicine, Rochester, New York (EM), Wayne State University School of Medicine, Detroit, Michigan (JF), and the University of Western Ontario, Department of Surgical Oncology, London, Ontario (JC)

Purpose: Extraprostatic disease will be manifest in a third of men after radical
prostatectomy. We present the long-term followup of a randomized clinical trial
of radiotherapy to reduce the risk of subsequent metastatic disease and death.
Materials and Methods: A total of 431 men with pT3N0M0 prostate cancer were
randomized to 60 to 64 Gy adjuvant radiotherapy or observation. The primary
study end point was metastasis-free survival.

Results: Of 425 eligible men 211 were randomized to observation and 214 to
adjuvant radiation. Of those men under observation 70 ultimately received radiotherapy.
Metastasis-free survival was significantly greater with radiotherapy
(93 of 214 events on the radiotherapy arm vs 114 of 211 events on observation;
HR 0.71; 95% CI 0.54, 0.94; p 5 0.016). Survival improved significantly with
adjuvant radiation (88 deaths of 214 on the radiotherapy arm vs 110 deaths of
211 on observation; HR 0.72; 95% CI 0.55, 0.96; p 5 0.023).
Conclusions: Adjuvant radiotherapy after radical prostatectomy for a man with
pT3N0M0 prostate cancer significantly reduces the risk of metastasis and increases
survival.
PSA 1.5 to 3.2 in 11 months. First 12 core biopsy on 2/10 negative in 11, atypical in 1. Second 13 core biopsy on 5/10 at Hopkins positive in 2 with Gleason 3+3 (focal). Robotic "Super VIP" Mani Menon on 8/10. Postoperative Gleason 3+4 (70%/30%). Focal ECE right posteriolateral mid. Negative margins, lymphs, seminal vesicles. First PSA on 9/14 <.1. Never incontinence +ED

goodlife
Veteran Member


Date Joined May 2009
Total Posts : 2691
   Posted 11/9/2010 6:37 PM (GMT -6)   
The other question I have is what is considered detectable PSA ? Many oncologists use.2, some use .5 as trigger points. Is this their level of "detectable", or do they use a much lower number.

With the ultrasensitive testing now, we can elect to do radiation at .05 or some very low number which is considered undetectable by most. That is my current plan, and is a QOL thing for me. As soon as I see an upward trend, I am prepared for raidation, which by some definitions is adjuvant because my PSA will still be undectable.
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
1 year psa (364 days) .01
15 month PSA <.01

julios
Regular Member


Date Joined Jun 2010
Total Posts : 38
   Posted 11/12/2010 12:01 PM (GMT -6)   
Casey

As for my RT/HT plans: I began ADT with a Shot of Lupron 3.5 months post RP. Two months later I begin RT using about 68 Gy to three involved pelvic lymph nodes and about 62 Gy to the tumor that remains in the prostate bed. The hope is that the ADT will shrink the lymph node tumors allowing a smaller RT dose. The exact Gy will be determined after the 2 months of ADT. A PET scan will clearly delineate the status of the tumors, in my case.

I think I have a pretty good medical team. I live in Santa Barbara. The medical oncologist also does research at UCLA. The radiation oncologist graduated from Havard, and interned at Dana Farber.

As I recal, your disease is similar to mine. What is the difference in your condition, and what are your plans?
Age 52

At Diagnosis of PCa, had Gleason 9 and normal PSA

Radical Prostatectomy on July 7th, 2010 by Dr. Fagin using daVinci

25% to 50% nerves spared on left, 100% spared on right.

Continent from day one.

Pathology showed postive margins and extension beyond gland, including seminal vesicals and lymph nodes. Stage upgraded to T3b.

sam NY
New Member


Date Joined Nov 2010
Total Posts : 3
   Posted 11/13/2010 8:47 AM (GMT -6)   
Am I missing something?
The study above makes a diagnosis of pT3N0M0 not look the best, "Metastasis-free survival was significantly greater with radiotherapy (93 of 214 events on the radiotherapy arm vs 114 of 211 events on observation)".
This would indicate almost a 50/50 chance of something happening.

By contrast if you go to
Prostate Cancer Nomograms: Post-Radical Prostatectomy
http://www.mskcc.org/applications/nomograms/Prostate/PostRadicalProstatectomy.aspx
and input similar data, (Extra Capsular Extension checked only) you get a much different picture,
Progression-Free Probability After Surgery 10 Year 87%
Probability of Prostate Cancer Mortality after Surgery 1%

Is this because the psa, gleason, year I'm typing in makes the difference?
Or is this Nomogram not accurate?
Or is it that the Nomogram assumes you gave a post op PSA that is undetectable? And perhaps the patients in the above had detectable PSA right off the bat?

One more study showing about an 80% chance of Progression-Free Probability with pT3a/sm-.
http://hal.archives-ouvertes.fr/docs/00/44/79/94/PDF/Figure_et_table.pdf

I am confused.

goodlife
Veteran Member


Date Joined May 2009
Total Posts : 2691
   Posted 11/13/2010 9:18 AM (GMT -6)   
Sam,
 
This is a confusing topic.  For as many searches as you do on the topic, you find as many opinions.
 
Nomograms are a statistical statement.  The studies are an observation of the sample at hand.  Stats say that heads or tales is a 50/50, however when you do it 100 times, it may be 30/70, or 70/30, or it may land on the edge once.
 
It is true , PT3NOMO is not the best diagnosis statistically, but you will find many guys here who are beating the odds.  The why is the tricky part.  Every trial may come up with a different conclusion based on what they are studying.
 
For me, it has become a personal choice of when I want to pull the radiation trigger.  So far, I figure I have potentially extended my longevity by a couple of years by waiting, if I can expect 10 yearspost radiation, which may be an entirely bogus belief and number.  With .01 PSA, I just am going to wait.
 
Oh, and welcome to the forum.
 
Goodlife
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