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New Study: Adjuvant Radiation Saves Lives vs. Salvage

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Tall Allen
Elite Member
Joined : Jul 2012
Posts : 10645
Posted 1/29/2018 12:59 PM (GMT -6)
This was a major retrospective study among post-prostatectomy patients with adverse pathology at 10 top institutions. It's about the best any retrospective study can do when prospective randomized clinical trials are not available. They found that in men with adverse pathology, adjuvant radiation led to less biochemical failure, less incidence of metastases, and better overall survival compared to salvage radiation. They defined salvage radiation (SRT) as radiation given when the PSA was in the 0.1-0.5 range. They couldn't address with this dataset what I would call "early salvage" (ultrasensitive PSA under 0.1).

/pcnrv.blogspot.com/2018/01/new-study-adjuvant-radiation-saves.html

Read the caveats at the end carefully.
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Saipan Paradise
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Posts : 1361
Posted 1/29/2018 2:20 PM (GMT -6)
Thank you, Allen. That’s super interesting for where I am right now, what I think you’d call early salvage. I read the caveats.
One paragraph I’m having particular trouble understanding:
The advantage of ART was only lost if more than 56% of them would have been overtreated, but based on nomograms, no more than 46% would have been overtreated (using the assumption that 2/3 were GS 3+4 and 1/3 was GS 4+3).
How is the tipping point for losing the advantage determined to be at 56%? Practically speaking, how does one use this information as a patient having to decide when to pull the trigger on RT? (I hope those questions make sense.)
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Progressing
Regular Member
Joined : Aug 2017
Posts : 334
Posted 1/29/2018 3:02 PM (GMT -6)
Thanks Allen for posting this. Reniforces my belief that ART is what we persisters need.

Still waiting four days after second post-surgery persistent psa to hear from the surgeon.

And after thinking some more, my plan now is to accept the cost of an apartment in the City and try to get Dr. Zelefsky to do the ART. Hoping that I can get an appointment with him soon — based on the two post-surgery readings my PSADT is 10 months, meaning it would hit 0.2 in October, by when I would hope to have finished ART. For now if I don’t hear from the surgeon tomorrow I will contact Dr. Zelefsky directly.
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RobLee
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Posts : 1370
Posted 1/29/2018 3:15 PM (GMT -6)
Interesting read, TA and if I may say so, I might well be the poster child for adjuvant HT and ART administered based solely upon adverse pathology, before any significant post-op PSA increase. Many of the stats in this study fit my case to a "T"... G8, SVI, -LNI. Based upon my first post-RT uPSA being 0.00 it looks like everything worked in my favor despite seemingly having everything going against me going in.

But one item in the nomogram puzzles me /pcnrv.blogspot.com/2016/08/probability-of-remaining-recurrence.html... I've gone thru the calculation before "as is" and was wondering why positive surgical margins appears to be favorable and negative margins unfavorable. Or do I misunderstand something?

In every other facet, more adverse pathology adds points to the score (Gleason, stage, +SVI, -ADT) while more favorable conditions score zero... except SM. Positive SM scores 0 and negative SM scores 27. Wouldn't it logically be the other way around?

Or am I seeing things backwards? confused

Risk Factor Score (points)
ADT Yes: 0 No: 49
Gleason score 6: 0 7: 54 8: 70 9/10: 90
Extraprostatic Extension No:0 Yes:22
Surgical Margins Positive: 0 Negative: 27
Seminal Vesicle Invasion No: 0 Yes: 24
Pre-RT PSA (ng/ml) 0.05: 2.5 0.1: 5 0.2:10 0.3: 15 0.5: 25 1.0: 50 1.5: 75
Radiation dose (Gy) ≥66 Gy: 0 <66 Gy: 17
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George_
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Posted 1/29/2018 3:26 PM (GMT -6)
Rob,

if you have positive margins, the recurrence is mostly located in the prostate bed and the radiation of the prostate bed will treat that. In case of negative margins chances are that there are affected lymph nodes and radiating just the prostate bed will not help much.

George
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Gemlin
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Joined : Jul 2015
Posts : 727
Posted 1/29/2018 3:27 PM (GMT -6)
RobLee-
A patient with positive margins who relapses is more likely to benefit from salvage radiotherapy than a patient with negative margins, whose PSA level is more likely to represent distant disease. With positive margins it is more likely a local disease that can successfully be radiated.
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Tall Allen
Elite Member
Joined : Jul 2012
Posts : 10645
Posted 1/29/2018 3:41 PM (GMT -6)

Saipan said...
How is the tipping point for losing the advantage determined to be at 56%? Practically speaking, how does one use this information as a patient having to decide when to pull the trigger on RT? (I hope those questions make sense.)

It's a very good question. It's explained in the full text. They did what is called a "sensitivity analysis" where they looked at only the records of those patients who received ART, but might have been cured by their surgery alone. Patients with GS 6 were only a small fraction of these patients, and GS 8-10 patients were highly likely to progress. That leaves GS 7s as the equivocal group. they were 57% of all patients in the study and they typically break about 2/3 GS 3+4 and about 1/3 GS 4+3. They looked at their nomogram-predicted cure rates vs the actual results. They found that ART would only lose its advantage if 56% were overtreated, but the nomogram-predicted overtreatment rate was only 46%. So on the whole, ART outcomes exceeded SRT even considering overtreatment. The whole does not necessarily predict for the individual, however, and each patient must look at his individual characteristics.
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RobLee
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Posts : 1370
Posted 1/29/2018 3:45 PM (GMT -6)
Thanks George and Gremlin... so in the case of positive SM's they know where the cancer is, but in the case of negative SM it must be elsewhere. "Better the devil you know than one you don't know".
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Tall Allen
Elite Member
Joined : Jul 2012
Posts : 10645
Posted 1/29/2018 3:46 PM (GMT -6)
Roblee-

While a positive margin is a risk for recurrence, it is also prognostic that SRT will work. That's because you have a really good clue that the cancer is still local. If they can't find a large enough tumor, the cancer might be micrometastatic and/or systemic.
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Progressing
Regular Member
Joined : Aug 2017
Posts : 334
Posted 1/29/2018 3:51 PM (GMT -6)
Saipan and Allen, od conversation, interesting to follow. The last sentence of Allen’s reply seems the most important — each of us is 100% likely to have his own unique characteristics and outcome, so even if someone happens to be one of those overtreated he may have unnecessary side effects, but I would think of the two risks SEs beat spreading cancer, and there’s no way to know except by foregoing the treatment and seeing what happens.
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Progressing
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Posts : 334
Posted 1/29/2018 3:53 PM (GMT -6)
Sorry, that should be “good” conversation.
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Saipan Paradise
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Posts : 1361
Posted 1/29/2018 4:08 PM (GMT -6)
Progressing—
That’s exactly mine and my wife’s feeling: we’re all in. The decision is where to do it, which RO to go with, and managing the logistics. In Orlando this week. Meeting with RO Dr Biagioli tomorrow and then my surgeon, Dr Patel, on Wednesday. Scheduled for Axumin PET tomorrow, too, and 3T MRI on Thursday. Oh, and in between, unrelated, my biannual cardio treadmill and echocardiogram. Fun fun fun.
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randrball1
Regular Member
Joined : Mar 2017
Posts : 31
Posted 1/29/2018 5:23 PM (GMT -6)
This study fit my situation after my RALP. My first psa returned as <.05, but my urologist kept insisting on me seeing a RO. I didn't need to see a RO as my PSA party was just beginning. Heck, it's undetectable and I'm almost convinced I've been cured. He kept mentioning data out there to support ART with my adverse pathology report. After some convincing, I reluctantly agreed to see a RO and it was that moment I saw relief in my urologist's eyes. He genuinely cared about me as a patient, person, father to an eleven year old, and a husband to my wife. However, I was still going to put up a fight with the RO since my PSA is undetectable, but in the end I did find myself fully committed to ART. The hardest part of the ART journey was not knowing if I was being overtreated, what side affects will I have, and the daily committment till treatment is over. Looking back, I still don't have all the answers, but pray I have beaten this disease so one day I can grow old and possibly walk my daughter down the isle. I am by no means advocating any type of treatment for anyone. This was my journey and the decisions came very difficult to make just as you guys will experience. What ever you guys decide about ART, god bless & best of luck.
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ddyss
Regular Member
Joined : Apr 2017
Posts : 499
Posted 1/29/2018 10:31 PM (GMT -6)
Would any doc/institution give ART if one doesn’t have an adverse pathology. I reached out to U chicago RO Dept and Dr Stanley Liauw’s response was “I think you should connect with a urologist at this point. we are in radiation oncology. if the pathology shows T2N0 and clear margins, and the PSA looks good then you will not need any other cancer therapt”
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Tony Crispino
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Joined : Dec 2006
Posts : 8151
Posted 1/29/2018 10:56 PM (GMT -6)
When I had my surgery in February of 2007, I had a bad enough post op pathology and went searching out the next steps. My PSA at the time of surgery was 20, by post op pathology was bilateral seminal vesicle invasion stage pT3b. My Gleason was 4+3=7. Positive margins as well.

After reviewing a possible clinical trial and also reading information out of Harvard and Stanford that guys like me were doing better with adjuvant therapies. My PSA did drop out to >0.1 from the surgery alone but at age 44 I wasn't thrilled with the nomograms and tables on recurrence. So we started ADT for two years and I started IMRT radiation all within 4 months of treatment.

I lucked out and never had a rise in PSA. I go in for my 11th year tests in a couple weeks. I haven't had a PSA test in two years but they've stayed good for me. After all these years I function well and live a cancer free life.

I will never know if the adjuvant therapies helped me. I suspect they did. To date I do not feel there are any side effects worth mentioning. I still have low T levels (below 250 ng/dl) but I get along fine.

I was one of the first to go this rout and I didn't know anyone here at HW at the time in 2006/07 that went that rout prior to me doing so. But I know a few that followed my path and they all seemed to do well.
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Tall Allen
Elite Member
Joined : Jul 2012
Posts : 10645
Posted 1/30/2018 1:19 AM (GMT -6)
ddys-

Why would a patient want ART unless he has adverse pathology? Even with adverse pathology, there are very few circumstances (maybe N1 or T4 or large, high grade positive margins) where it doesn't pay to wait for a 3-month uPSA and some healing to occur.
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ddyss
Regular Member
Joined : Apr 2017
Posts : 499
Posted 1/30/2018 3:04 AM (GMT -6)
TA,
I’ve seen very few cases who chose surgery on this board that were stage T2c and no adverse path who have not had BCR - most had BCR after than 2 years and in some more than 5 years and a few after 7 years. So my assumption is BCR is going to happen eventually to me and what you shared shows it’s better to go with ART now than to eventually wait for Salvage , shouldn’t a patient be given the option to get ARt done. I am ok to deal with SEs related to ART than deal with BCR.
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Saipan Paradise
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Joined : Sep 2017
Posts : 1361
Posted 1/30/2018 4:09 AM (GMT -6)
ddyss,
More and more it looks to me like patients who are already high risk at biopsy (or at high risk of upgrading to high risk in the post-surgical pathology report) shouldn’t be presented with surgery as a first line option unless the patient has specific hx that contraindicates radiotherapy. Why would one initially choose a triple play of surgery followed by HT & RT over a triple play of brachy+IMRT+HT? I went into surgery believing it had a better than average chance of being curative by itself. If someone had told me HT was most likely in my near future anyway, why would I have stoically accepted the SEs of surgery? It’s emotionally draining to face a second extended period of tx and recovery so soon after completing the first. I’m still waiting for a good night’s sleep during my little tour of the Best ROs of Florida. Sucks.
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Progressing
Regular Member
Joined : Aug 2017
Posts : 334
Posted 1/30/2018 7:50 AM (GMT -6)
Roger that Saipan. The only consolation if it is one is that we know we have recurrence now, rather than seeing a rising psa after the post-RT nadir, which may mean that we’ll get adjuvant rather than salvage second treatments. Still sucks.
“i can get it all,” said the surgeon, and then, “I got it all,” without saying in either case that there might be cancer lurking somewhere. In my case the tumor was on one side only, no multicentricity, and the fat adjacent on that side was also benign. Hope that doesn’t mean it’s migrated so that RT would be useless, but it appears there’s no way to know at psa level of 0.11.
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RobLee
Veteran Member
Joined : Apr 2017
Posts : 1370
Posted 1/30/2018 8:25 AM (GMT -6)

Progressing said...
“i can get it all,” said the surgeon, and then, “I got it all,”

I never heard either of those, but I did hear "we got most of the cancer," and then "you will need radiation in six months." Then I heard three years of HT. Some days we chase the bear and other days the bear chases us. You just have to take it in stride.
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Tall Allen
Elite Member
Joined : Jul 2012
Posts : 10645
Posted 1/30/2018 10:31 AM (GMT -6)

ddyss said...
I’ve seen very few cases who chose surgery on this board that were stage T2c and no adverse path who have not had BCR - most had BCR after than 2 years and in some more than 5 years and a few after 7 years.

That's a big problem with boards like this. Many of us come here because there is a problem, and the ones who have no problem don't come here. So we get a very slanted pictures of the real probability of progression. In the new AJCC staging system that went into effect starting this month, there is no such thing as pathological stage T2c. One has cancer either confined to prostate (pT2) or not. They got rid of the subcategories because statistics showed that it really didn't matter if it was on one side or both sides, only that it was contained.

To understand your real statistical probability of a recurrence, you'll want to look at a nomogram based on the experience of thousands of men. The best one I know is the MSK nomogram (you will notice that it doesn't even ask for the stage T2 subcategories - they are irrelevant to prognosis):

/www.mskcc.org/nomograms/prostate/post_op

I think you'll see that your probability of recurrence is very low. Out there in the real world, most men with your diagnosis never need any additional treatment. It's certainly safe for you to just monitor uPSA occasionally.
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ddyss
Regular Member
Joined : Apr 2017
Posts : 499
Posted 1/30/2018 11:39 AM (GMT -6)
Thanks for the reassurance TA and I hope you are right and I certainly hope MKCC nomogram is accurate- I have 89% chance of being recurrence free in 10 years. I wonder why they ask age as an input when it really doesn’t change the output, they must be gathering age based data.

Saipan/Progressing , have been following you on your other threads. All the best in your next step, you are showing a lot of poise and courage.

I am starting bupropion to get me through this phase.

Post Edited (ddyss) : 1/30/2018 10:43:40 AM (GMT-7)

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Progressing
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Joined : Aug 2017
Posts : 334
Posted 1/30/2018 12:50 PM (GMT -6)
Thanks ddyss, for your kind words.
And Tall Allen also — for the depth of your understanding of prostate cancer and those who have it.
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Saipan Paradise
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Joined : Sep 2017
Posts : 1361
Posted 1/30/2018 6:21 PM (GMT -6)
Thanks ddyss, Progressing, TA.
Meeting with Dr Biagioli was a home run. He had clearly read and thought about my pathology reports and tx history carefully, discussed the scientific evidence pro and con various tx options in a way I could follow but without my feeling talked down to. Afterward I felt truly hopeful for the first time in quite a while. I’m inclined to do RT and HT with him, if I can make it work logistically. 72 Gy/40 fractions, 6 months Lupron, no WPRT, based on low PSA and positive margin would treat recurrence as localized.
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Progressing
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Posts : 334
Posted 1/31/2018 8:05 AM (GMT -6)
Great to hear, Saipan. You had posted something earlier about knowing when you would find the right RO for you and how important that is. As many people have counselled me, now relax and go for it!
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