HealingWell
Search Close Search
☰

When should the patient and doctor consider salvage radiation therapy?

Support Forums
>
Prostate Cancer
✚ New Topic ✚ Reply
1 2 3
❬ ❬ Previous Thread |Next Thread ❭ ❭
Posted 2/10/2015 8:20 PM (GMT -5)
No. Adjuvant (Arm A) had slightly better OS than wait-and-see (Arm B), but the difference wasn't statistically significant - the ARO 96-02 study was underpowered to detect a difference.
Posted 2/10/2015 11:20 PM (GMT -5)

Rigby said...
I guess I'm past the Adjuvant stage (Arm B) already, but wait and see came out better than adjuvant?


"The Kaplan-Meier method was used to analyze overall survival (OS). Patients in Arm A had a 10-year OS rate of 86 percent, and patients in Arm B had a 10-year OS rate of 83 percent, compared with patients in Arm C who had a 10-year OS rate of 68 percent."

Something about trying to read this study is messing with my mind.

German study said...
Prior to reaching an undetectable PSA post-prostatectomy, 159 patients were randomized to a wait-and-see approach (Arm A) and 148 patients were randomized to receive adjuvant radiation therapy (Arm B).

So OK, is this saying that, BEFORE any post op PSAs were measured, arm A was randomized to no extra treatment, and arm B got aRT?

Somebody said...
Seventy-eight patients who did not achieve an undetectable PSA were moved to Arm C. Four of the patients in Arm C refused treatment, and 74 patients were treated with salvage radiation therapy in Arm C.

And then once they did measure PSA, and found it to be detectable, they were move to arm C for salvage, right?

So this means that both A and B had undetectable post surgery PSAs presumably at some early period like 6 weeks or maybe up to 3 months? Do we know? Do we know what undetectable was? <.01? <.1?

Regardless, the 2 groups with "undetectable" PSAs, whatever and whenever that was, had a 3% difference in the high 10 year overall survival rate, and the advantage was actually to group A( randomized to a wait-and-see approach (Arm A))? WTH? I was all ready to say that is not much of an advantage for the aRT group, probably not quite significant, until I realized the advantage went to wait and see for the 2 groups with "undetectable".

I think I must be reading this wrong, somebody please straighten me out.

As for "Clinical relapse-free survival (cRFS) was calculated using the Kaplan-Meier method. In Arm C, patients had a 10-year cRFS rate of 63 percent.". Do we know the cRFS of the other groups?

Oh well, just another study, eh? I keep asking "which study do you prefer?". In the "undetectable" groups of arm A and B, unless most or all of both groups had < .03, then wouldn't some of them probably be going on to BCR? (maybe indeed they were all <.03?) But if they were only <.05 or even only <.1, then you would think at least some of them would have been >.03 and would be heading to BCR and would have benefited from aRT. But apparently not. Sure would like to know what that "undetectable" level was.
Posted 2/10/2015 11:23 PM (GMT -5)

Tall Allen said...
No. Adjuvant (Arm A) had slightly better OS than wait-and-see (Arm B), but the difference wasn't statistically significant - the ARO 96-02 study was underpowered to detect a difference.

I thought arm A was wait and see?

Somebody said...
159 patients were randomized to a wait-and-see approach (Arm A)

and aRT was arm B?

Somebody said...
and 148 patients were randomized to receive adjuvant radiation therapy (Arm B).

?

EDIT: also, isn't this an awfully high rate of not reaching undetectable?

study said...
ARO 96-02 accrued 388 patients from 1997 to 2004 with pT3-4pN0 prostate cancer with positive or negative margins who had already undergone radical prostatectomy. ......... Seventy-eight patients who did not achieve an undetectable PSA were moved to Arm C.

That did not leave many patients for the other arms, maybe 150 each, so it probably was underpowered. Still, I am surprised at the results.

Post Edited (BillyBob@388) : 2/10/2015 9:44:20 PM (GMT-7)

Posted 2/11/2015 12:13 AM (GMT -5)
Well, just like "don't do psa tests", "wait and see" doesn't make any sense to me. If nothing else, maybe any kind of treatment buys time until someone finally figures this out.
Posted 2/11/2015 12:26 AM (GMT -5)
BillyBob-
Yes, you are very confused. As I just wrote - Group A was adjuvant, Group B was wait-and-see. Read the link to the ARO 96-02 study in my article again.
- Allen
Posted 2/11/2015 9:40 AM (GMT -5)

Tall Allen said...
BillyBob-
Yes, you are very confused. As I just wrote - Group A was adjuvant, Group B was wait-and-see. Read the link to the ARO 96-02 study in my article again.
- Allen

OK, sorry, but I did not originally follow the link from you article, even though I read the entire article ans all of the comments including Ask Arthur(?) and found it all very interesting, and I thank you for this info. But I just skimmed back through your article and did not see(I'm sure I just overlooked it) the link to this ARP 96-02 study. But are we looking at different studies and/or links? From my 1st post on this study I was following this link from Jane's post, as apparently Rigby also did leading him to the same confusion as me:

Jane B. said...
I saw this today and dug it out of the computer trash. Could this be a help in someone's decision making?

http://www.medicalnewstoday.com/releases/289114.php?tw

Jane B.

And I have copied and pasted from that report of something called "Ten-year post-treatment analysis of German ARO 96-02" this:
"159 patients were randomized to a wait-and-see approach (Arm A)" and " and "148 patients were randomized to receive adjuvant radiation therapy (Arm B)" Arm A= wait and see. Arm b = aRT/adjuvant
vs
TA "As I just wrote - Group A was adjuvant".

Since I am copying and pasting all of this, I am either having a mental issue(and I just had another person double check this with me to help guard against that) or we must be looking at different sources?

But, either way, it is not that important. If A was indeed aRT, then there was- at least in this one small study- a very small advantage- probably not even statistically significant or barely so- for 10 year OVERALL survival in the group which got aRT. At least in the men who had undetectable post op PSAs. Maybe underpowered like you said.

The men in arm C, who had detectable PSA post op, and received salvage RT plus some also had HT, had a 10-year OS rate of 68 percent, vs the 86 and 83 in A and B.

EDIT: OK, I found the link from your article, here:
http://www.sciencedirect.com/science/article/pii/S0302283814002474
and it does seem to read differently.

EDIT #2: I don't have access to the full article. Based on the summary at the above link, there is no mention of which is arm A, B or C. And groiup C does not seem to be discussed in this summary, only those with undetectable PSAs at the start. Also

article said...
The median follow-up was 111 mo for ART and 113 mo for WS. At 10 yr, PFS was 56% for ART and 35% for WS (p < 0.0001). In pT3b and R1 patients, the rates for WS even dropped to 28% and 27%, respectively. Of all 307 ITT2 patients, 15 died from PCa, and 28 died for other or unknown reasons. Neither metastasis-free survival nor overall survival was significantly improved by ART. However, the study was underpowered for these end points. The worst late sequelae in the ART cohort were one grade 3 and three grade 2 cases of bladder toxicity and two grade 2 cases of rectum toxicity. No grade 4 events occurred.
Conclusions

Compared with WS, ART reduced the risk of (biochemical) progression with a hazard ratio of 0.51 in pT3 PCa. With only one grade 3 case of late toxicity, ART was safe.

So, At 10 yr, PFS was 56% for ART and 35% for WS (p < 0.0001)., an advantage for progression free survival for the aRT group. And an even bigger advantage for T3B. But "Neither metastasis-free survival nor overall survival was significantly improved by ART."

One stand out for me from reading your link is that ONLY 56% for ART and 35% for WS, of men who had undetectable PSA, had progression free survival . In pT3b and R1 patients, the rates for WS even dropped to 28% and 27%, respectively.

But I guess the other take away is that "Of all 307 ITT2 patients, 15 died from PCa, and 28 died for other or unknown reasons". Whether they got aRT or not, only 15 out of 307 died of PC.

Post Edited (BillyBob@388) : 2/11/2015 8:13:34 AM (GMT-7)

Posted 2/11/2015 11:26 AM (GMT -5)
That's why I don't take information from random sites on the internet, and very seldom look at them when posters provide them (in addition to risk of malware). I'm a stickler about sources. My preferred source is always a peer-reviewed professional publication.
Posted 2/11/2015 12:51 PM (GMT -5)

Tall Allen said...
That's why I don't take information from random sites on the internet, and very seldom look at them when posters provide them (in addition to risk of malware). I'm a stickler about sources. My preferred source is always a peer-reviewed professional publication.

So that must be a misquote from the original link I followed- to Medical News Today- provided by Jane B?

But still, I found more detail following the link you provided in your article and then clicking on the PDF button which appears to finally give me the full article, which was here:
www.europeanurology.com/article/S0302-2838%2814%2900247-4/pdf/adjuvant-radiotherapy-versus-wait-and-see-after-radical-prostatectomy-10-year-follow-up-of-the-aro-96-02-auo-ap-09-95-trial

But it is the same over here, where it says:

Europeanurology said...
Before achieving a post-RP undetectable PSA, patients were
randomized to either wait-and-see (WS) (arm A) or ART (arm B).

wait-and-see (WS) (arm A)

or ART (arm B)

Also,

Europeanurology said...
In ITT2, 49 WS and 41 ART patients received salvage HT.............Subgroup analysis shows a significant advantage from ARTfor men withpositive surgical margins and tumor stage
pT3a/b (Fig. 3). For pT3b alone, the 10-yr PFS was 28% (WS)versus 47% (RT) (BB says: pretty good aRT advantage there)..........

Twenty-two WS ( ~ 14%) versus 25( BB's calc ~ 17%) ART men developed
distant metastases .........

Twenty WS( BB's calc= ~13%) and 23 ART patients(BB's calc = ~16%) died during 14 yr of follow-up. For the
latter end points, events are too rare to achieve sufficient
statistical power .

( all of my approximate calculations based on 159 men followed up in the WS arm A, and 148 in the aRT arm B)

So, it appears that the overall survival rate for the WS Arm A group was about 87%, and for the aRT group it was about 84%, and the distant met rate for WS was about 14% vs 17% for the aRT group. Although, those % might change a bit if I am using the wrong numbers in each group that was followed up. What it amounts to is no significant difference in OS or distant mets for either group. But, a much better result for being progression free with the aRT.
Bill

Post Edited (BillyBob@388) : 2/11/2015 11:00:11 AM (GMT-7)

Posted 2/11/2015 1:49 PM (GMT -5)
When they presented it at the Genitourinary Cancer Symposium in 2013, they wrote "385 men with prostate cancer were randomized to either 60 Gy RT (arm A; n=193) or WS (arm B; n=192) before achieving an undetectable PSA."

meetinglibrary.asco.org/content/107383-134

So it appears that they reversed what they labeled as A and B in the two publications.

However, that doesn't matter. What matters is that Adjuvant outperformed Wait-and-See on their primary endpoint - biochemical no evidence of disease (bNED) - "At 10 yr, PFS was 56% for ART and 35% for WS "

The study was underpowered to detect all other endpoints, as I repeatedly stress. I understand why we are tempted to draw statistically indefensible conclusions from the data, but the data really doesn't allow that. We have to wait for clinical trials designed for that purpose, or look to retrospective studies, understanding they are often wrong.

- Allen

Post Edited (Tall Allen) : 2/11/2015 11:57:23 AM (GMT-7)

Posted 2/11/2015 5:06 PM (GMT -5)
Allen, I agree. It does not matter. But if you ever feel like you have too much time on your hands(HaHa!, I doubt that) and you feel like teaching a course on statistics, maybe you can try to help us understand why the study is powerful enough to draw firm conclusions about PFS(if it indeed is) but at the same time underpowered for drawing conclusions about overall survival(OS) and the rate of distant mets, etc. I know I take up a lot of explanation time, due to my ignorance of statistical methods.

It is also probably also statistically indefensible to draw conclusions from the death rates also, even without breaking those rates down into groups. I don't know enough about statistics to know if it is or isn't. Still, I can't help but take note of the fact that, of all 307 ITT2 patients, including those with aRT, without aRT and those whose PSAs never went undetectable and who went right to salvage, only 15 (5%) died from PCa, and 28(9%) died for other or unknown reasons.

EDIT: on reading some more just now, it appears the 307 ITT2 patients ONLY included those whose PSAs did reach undetectable levels. So of that group 5% died pf PCA. I suppose the other group of 70 some men whose PSAs never went undetectable had a higher PC death rate than the other group.

Post Edited (BillyBob@388) : 2/11/2015 3:24:10 PM (GMT-7)

Posted 2/11/2015 5:29 PM (GMT -5)
Oh, and joy of joys, I finally found where they state what levels were considered undetectable. Turns out it varies, I suppose by locale:
"These patients all had a PSA<0.1 ng/ml,

80% had a PSA<0.05 ng/ml,

and 41% had a PSA of even<0.03 ng/ml,

depending on the detection limits of the different assays."
Posted 2/11/2015 6:26 PM (GMT -5)
Billybob-

I can't teach a statistics course here, but if you don't want to rely on the authors' assessments, the basic concepts you have to master for the study you're looking at are: statistical significance, statistical power, hypothesis testing, inferiority/superiority, and Kaplan-Meier curves. Since you seem interested, maybe your local university extension offers classes. Or you can trust that in a peer-reviewed publication, their stats will be correct.

As I wrote in a different article on ultrasensitive PSA (uPSA)tests, none of the 3 RCTs on adjuvant vs wait-and-see used uPSA to any appreciable degree.

- Allen
Posted 3/10/2015 1:43 PM (GMT -5)
Tall Allen (and/or others)
I'm resurrecting your thread seeking some guidance. I see Dr. Myers this Friday. My PSA crept up to 0.181 last month and is 0.182 this month. I increased my level of exercise between the two on Dana's recommendation, but I don't know if that's why it stopped this time. I'm walking 3.5 to 5 miles per day now. Anyway, earlier in this thread you say IMRT is the type of radiation that would be used for my case for SRT. Also, in the comments from Catalona you agreed that the actual person doing the treatment isn't as important as in other types of radiation. Still, I want to give myself the best shot at cure if it is still a possibility. So, in the same vein that I have been on (going to a super doc surgeon, and then a super doc MO) what questions should I be asking or what better treatments might be available? How do I find a great RO in my area? I live in Cary, IL about an hour NW of Chicago. Westmont is not far away where Dr. Moran is, but I think he is only brachytherapy.

I think my case is actually a good lesson for newbies as I consider it now. I went for the cure with the best surgeon I could find nearby based on my tests and recommendation from a local urologist. But it didn't work because the tests are not accurate enough to detect escaped cancer. So then I went to Myers in hopes of cure without radiation side effects which I thought would be major. But of course I hope to avoid hormone treatments too. The Avodart Metformin Crestor treatment might be what's keeping it at bay now. If I had found other resources earlier and visited each specialty first, and if the recent studies you have posted were known to me I would most likely have chosen brachy. Catalona said he thought he could take care of it, with a little smile. And I felt I was in better shape than average to come out of surgery without major SE's. I suppose we all feel we are better than average in that way. We all say continence and potency are of secondary importance but if the surgery doesn't work they become much bigger burdens. I'm finally down to occasional sneezing incontinence, but ED is still bad. I guess I'm only half better than average :-). But I'm still not on a path to cure. What I would hate to happen is to risk more/worse SE's from radiation and then still end up living my life on Myer's plan. I would then have gotten the triple whammy of SE's without cure. I suspect he will say this time that my PSA is manageable but my fear is it won't be for long and I'll just be starting that much later with radiation when it really won't offer the chance for cure.

Sorry to run on so long. You can probably tell I'm frustrated.

Jim
Posted 3/10/2015 2:44 PM (GMT -5)
Jim,

I've got to admit that I'm not such a big fan of consults with medical oncologists for guys in your situation, as some are on this site. It's the hammer/nail problem - they see a lot of men who are well along in their disease progression, and tend to approach patients from that POV. For someone like you, who has a good chance of cure from salvage radiation, I think a radiation oncologist is a better choice - and will save you lots of money.

The variables in salvage radiation treatment are such as:
• use of fiducials/Calypso to track prostate bed position.
• whether neoadjuvant/adjuvant ADT is necessary.
• treatment of pelvic lymph nodes concurrently.
• mildly hypofractionated treatment (2.5 Gy/treatment over 5 weeks instead of 2.0 Gy/treatment over 7 weeks)
• use of an immune enhancer to enhance the abscopal effect. (This is something Snuffy may be able to help with - I know he is an advocate of Leukine, and he may somehow be able to get it insurance-covered for you.)

- Allen
Posted 3/10/2015 3:52 PM (GMT -5)
Thanks much. I forgot to ask if I should have my pathology report from the surgery read by Epstein or one of the other gurus? I keep thinking it would help to locate the escape path, and might change the gleason assessment. The other thing I keep thinking is if I was 8 at biopsy, then 3+4 after surgery, it's the 4's that got out and that puts me in a worse state.

Jim
Posted 3/10/2015 4:16 PM (GMT -5)
I'm only one example, but I just completed 33 SRT treatments two weeks ago, and as far as I could tell, had ZERO side effects then and now. I had the Calypso implants, which seemed like a great idea, and also had a bowel movement every one of those 33 mornings and I live 10 minutes from the hospital so going in with a full bladder wasn't a problem. Maybe all those things helped, or maybe I was just lucky. Whether it worked or not has yet to be determined, my RO gives my case a 1/3 chance, the MSKCC nomogram puts it at 54% with my numbers. I wish you all the best and hope it works for you.
Posted 3/10/2015 4:42 PM (GMT -5)
Glad this thread came back up. I am in the middle of testing before SRT. Having colonoscopy on Thursday then will go back to RO to set start date. My Surgeon said higher than 50% chance, MSKCC showed 59%, RO
said better than 80% chance of success. Both surgeon and RO said no hormones with treatment - glad of that for sure. No implants- just tattoos. 70g's 7 weeks Ready to go
Posted 3/10/2015 4:51 PM (GMT -5)
It's not really critical to get a second opinion on your post-op pathology. It takes a lot less skill when they have the whole prostate to look at - problems like sampling and core angle go away.

You were stage pT3a, so that pretty well tells you the escape path. It's almost always in the prostate fossa if it's still local.

- Allen
Posted 3/10/2015 9:41 PM (GMT -5)
Thank you Allen, and thank you also to others who have shared their experiences with radiation. My brother went through it with pretty minimal problems, at least according to him. So I think I'm getting adjusted to the idea that I need to do something more proactive.

Thanks again to all,
Jim
✚ New Topic ✚ Reply
123