Hormone therapy vs all cause mortality

Somebody said...
"There are some people who really benefit, and some people who don’t benefit, and some people who just might be harmed," he added. "So, we can be much more thoughtful and cautious in the future. From here on out, I’m going to be a lot more cautious with my patients."

Disclosures:

Spratt serves on the advisory board of Janssen and Blue Earth and has received funding from Janssen.

mattam said...
No additional anxiety for me Bill. Uncontrolled mets are pretty darned hazardous. 😉

No doubt! I do not think you were in the category they are raising a caution about!

Billybob, good post, thanks for sharing. I am saving this study just in case.
With that said, two points...
1. i agree with Mattam, PC Mets scare the hell out of me.
2. i think most of us already knew that HT puts us at risk for a variety of non PCa threats to our health. Its well known that HT can wreak havoc with lipids, cause Metabolic Syndrome that may lead to Diabetes, etc.
If i experience recurrence after SRT, i probably would accept ADT, but i cant say that 100% for sure right now, after my initial short term experience with Lupron/Firmagon

Bottom line, when it comes to PCa treatment, there ain't no free lunch.

Pratoman said...
Billybob, good post, thanks for sharing. I am saving this study just in case..........................

Bottom line, when it comes to PCa treatment, there ain't no free lunch.

Truer words were never written. Ask me how I know.(not really, you probably already know how I know)

Post Edited (BillyBob@388) : 9/19/2019 12:55:58 PM (GMT-6)

garyi said...
After surgery, then S(A)RT, and a still rising PSA, options become even less palatable...

https://onlinelibrary.wiley.com/doi/full/10.1111/bju.13926

here's the link in clickable format...

https://onlinelibrary.wiley.com/doi/full/10.1111/bju.13926

Looks like, effectively a 10% difference (from memory, maybe it was 11) for 6 year freedom from distant mets between ADT vs no ADT with SRT. Consistent with what i was told by my RO.
But many other variables with similar differences.

PDL17 said...
It seems to me that after surgery there is now greater "proof" that starting radiation sooner is better than waiting. I am not convinced that starting as low as >.03 always makes sense, though.

I was wondering where you were at BillyBob. Good to have you back.

Paul

Thanks, Paul! Yeah, starting as low as >.03 does seem a bit quick. Of course, I (or my docs) obviously think so, as I(mr. Hi risk) have been at .06 for quite a while(and am over due for a test, got to call them)

steve0 said...
All of this is so confusing.... I am right at the point of maybe having to make that decision. I go for another blood test in Dec and then the MO in Jan and maybe have to make a decision. At 73 years old and still walking around it is hard to fathom of all the SE of ADT. Don't know what I will do...

Steve, I know, it is confusing!

Billy, thnx for that study the one thing we have to remember is that we are a bunch of amateurs looking at these studies so if there is ever a reason to find ourselves a great team in our PCA journey this is it. I am so thankful that I was able to go to the Mayo! I think of the members we have here on our forum that have been on ADT for a while one that comes to mind is Todd. He didn't hesitate to go back on Lupron when his numbers started up a few weeks ago and hopefully he can get another 10 yrs and another ADT vacation along the way. As I'm sitting here with sweat running off me and my fingers curled up making it hard to type I can tell you that SE's suck but in a couple of hrs I'm taking off with the camper to spend the weekend with my grandson so yea if things don't go good at my check-up in Oct I will continue with treatment because the alternative sure the heck is a lot worse!!!! JMHO

Larry

Lots of goof points! PDA, interesting that "the catch-22s of cancer research. By the time you follow the subjects long enough...... How many of the men in the high-PSA group had those high readings because they waited a long time while the PSA rose slowly and how many had really short doubling times?.... Also, the ADT in the study was high-dose bicalutamide (an antiandrogen). I don't think there are that many of us here on the forum who have gone with an anti-androgen mono-therapy for ADT.".

Also, it is the lower PSA group that had the greatest increase in risk of all cause mortality.

Somebody said...
They found that — as in the original trial — patients with PSAs higher than 1.5 ng/mL showed improved overall survival (HR 0.45 [0.25-0.81]). For men with PSA levels lower than 1.5 ng/mL, however, there was no survival benefit (HR 0.87 [0.66-1.16]).

Spratt and colleagues also assessed the data for the subset of patients with PSA levels less than or equal to 0.6 ng/mL, which they noted is closer to today’s standard for post-surgical radiation treatment (as opposed to the standard at the time the RTOG 9601 trial was enrolling patients, when PSA levels were allowed to rise before initiating radiation therapy). And that data, Spratt said, "demonstrates that men with lower PSAs are more harmed than helped by long-term hormone therapy."

"We have now 3 randomized trials with over 2,400 men that do not demonstrate that short- or long-term hormone therapy improves overall survival in men receiving early salvage radiotherapy at low PSAs," said Spratt. "PSA prior to salvage radiotherapy predicts who will benefit most from hormone therapy and guidelines should now be updated to reflect this finding.",,,,,,,,,,,

............................................................................................................................................................................................

So, as others have pointed out, once you have mets or are likely to(higher PSA), those who really need the HT, you have to go with HT. What with mets being the likely alternative to not doing so, which is more dangerous to you than the increase in all cause mortality(ACM), if any.

Isn't it odd that the lower the PSA when SRT/HT is started, the greater the increase in ACM? And just as odd: the men with the higher PSA at the start- presumably the ones at higher risk for PC specifc death- not only had a lower risk of death from PC- but also less all cause mortality, rather than worse as in the low PSA group. What's up with that?

Whatever damage to the system that HT might cause along with damage to PC cells- wouldn't it cause just as much system damage in the guys with higher PSA, and increase- rather than decrease- their ACM, same as the low PSA group? That one is warping my mind.

I'd like to see the all cause mortality rates for the low PSA placebo group to compare to the same for the high PSA placebo group. Could there be some over all health characteristic in the lower PSA group, that would have given them lower ACM, compared to the higher PSA group? That is, before this theoretical advantage was damaged by HT? I'm just making wild ass guesses here guys, for what could account for improved ACM in the high PSA group vs worsened ACM in the low PSA group. ?????????????????????????

One more question: is PC specific death included in the ACM #s? Or do they remove PC specific death from the ACM #s, wanting to look at everything but death from PC? If so, if the numbers were great enough to influence the over all averages, wouldn't you expect the higher risk guys to have greater reduction in PC specific death due to HT, compared to the lower risk guys who had a much lower chance of PC specific death to start with? And if included in the ACM, wouldn't therefore ACM be improved? Again, just guessing wild here guys. I have no clue.

Thanks, PDA.

But,

Somebody said...
I still think if you look at the part describing the worse mortality in the low PSA group you will see that you misread.................It said...
A secondary analysis of the NRG Oncology/RTOG 9601 randomized, phase III clinical trial determined that a subset of 389 patients with a PSA of 0.6 ng/mL or less were twice as likely to die from causes other than their cancer when hormone therapy was added. [ emphasis mine ].........

No, actually, I saw that, and I think I understand the facts they are reporting. My question is "WHY" are they twice as likely to die from causes other than cancer when HT is added, while the high risk group actually had an improvement. However,

Somebody said...
I think the increase in Other Cause Mortality for the low vs high PSA group may be explainable by the fact that in the high-PSA group, despite being helped by the ADT in terms of overall mortality, enough of them died of PCa to reduce their Other Cause Mortality figure.

may be at least part of that explanation. In fact, I think I was trying to hint at the same possibility at the end of my last post.

OK then, how about this one: If the lower PSA guys are kept by HT from being killed by PC, then this will leave more available to fall into the ACM group, whereas some additional numbers in the placebo group would die of PC and thus not die from other than PC. I doubt that is enough to account for a doubling in ACM risk for the low PSA group, but perhaps it accounted for some of the increase in ACM seen for them? Or, have the researchers adjusted for all of that? I have not yet been able to find that, but I won't be surprised f they already adjusted for those possibilities. If not, it could alter the numbers, seems to me. Here is another link on this study:
https://www.medpagetoday.com/meetingcoverage/astro/82181

https://www.medpagetoday.com/meetingcoverage/astro/82181

Somebody said...
.........................................................
Finally, when the trial was enrolling, it was standard to allow PSA to rise to higher levels before starting radiation; today urologists typically refer patients before their post-prostatectomy PSA levels reach 0.2 ng/mL.

For this reason, Spratt's group sought to reanalyze the RTOG 9601 findings with more modern PSA cutoffs, focusing on the 85% of patients that fell into the 0.2-1.5 ng/mL range, a prespecified stratification variable of the trial. At 12 years, there was no significant survival difference between bicalutamide and placebo for patients with PSAs in this range (77% vs 76%, respectively; P=0.36).

They also examined outcomes by the trial's median PSA (0.6 ng/mL) and the median PSAs of the more contemporary GETUG-16 and SPPORT trials (0.2-0.3 ng/mL).

"Above 0.6, there's a survival benefit consistent with the overall trial," Spratt told MedPage Today. "So I think that we would need more data to withhold hormone therapy in those patients."

For patients in the 0.5-0.6 ng/mL range, "They're the ones who I would say, 'It's not wrong to have hormones, but you definitely don't have to do hormones,'" said Horwitz.

No overall survival benefit with ADT was seen below this cutoff, however, and interaction testing showed a trend toward harm at the lowest PSA levels (P for interaction=0.02):

>1.5 ng/mL (HR 0.45, 95% CI 0.25-0.81)

>0.6-1.5 ng/mL (HR 0.61, 95% CI 0.39-0.94)

>0.3-0.6 ng/mL (HR 0.94, 95% CI 0.59-1.50)

0.2-0.3 ng/mL (HR 1.78, 95% CI 0.88-3.57)

And while distant metastasis-free survival was improved in the group with the highest PSA, no benefit was seen for patients with the lowest levels (P for interaction=0.03).

"We now know there's a certain group of men who do benefit from the combination of hormones plus radiation for a PSA recurrence after surgery, but it's still not everybody," Horwitz said.

trailguy said...
I am sure that we are all clear as to my dislike of leuprolide chemotherapy...also my dislike of the current minimizing of same by referring to it as only "androgen deprivation" or "hormone therapy".... something that we should all bear in mind... for many of us there are no other options - literally.

I am inclined to say something here, exactly what, I'm not sure. Lupron pretty much saved my life, Granted, right now I'm out of the woods but am still surrounded by trees. Post-op my PSA was rising, though very slowly. Adjuvant RT was necessary due to adverse pathology, and Lupron bought me some time. Still, even on HT, it rose. Who knows how fast it might have doubled without it.

What followed was the usual SE's... hot flashes, night sweats, major depression, sarcopenia, cognitive impairment, hair loss. All not unexpected. Also my doc was getting on me about things like A1C, BP, heart rate, lipids... stuff with which I'd never had a problem. I blamed it on Lupron, and I suppose now, just hypogonadism in general. I didn't know anything when my RO recommended ADT. I didn't want to do anything wrong. Lord knows everything else went wrong anyway, I didn't want to interfere with my own cancer treatment.

Which brings me to the main point, which is that I am fed up with prostate cancer being treated as though it were not a real cancer, and it's treatments being diminished or belittled by the medical community and the public in general.... that our illness is treated as though what we have is nothing more than menopause and the perception of our treatments is in effect that we are merely taking supplements. We don't wear scarves on our heads and put pink ribbons on our cars and have people tell us to "be strong" or whatever. We get to suffer in silence. Yes, it is what's expected of men.

Unless we are already "terminal" (stage IV mets) we don't even get to see a real oncologist.

Regarding the article, my reading comprehension has suffered so drastically that I am unable to filter thru the stats and terminology. Hard to believe that I was once an intelligent person. In that regard, Lupron and the resulting hypogonadism has ruined my quality of life. I am unable to even hold interest in TV shows. News programming becomes boring and I spend most of my time listening to music... as long as there are no lyrics.

I'm with Trailguy... it's truly disheartening that "our" cancer and it's treatment is the Rodney Dangerfield of oncology. Yes, we can mention the names of dozens of famous people who died from prostate cancer. But mention it socially and people look the other way. We get no respect.

My wife was Dx'd with NHL soon after my RP and had six months of chemo during the time that I was started on Lupron. We would joke about her chemo brain vs my Lupron brain, and that we had one whole brain between the two of us. In cancer chat some would ask which one of us had use of the brain that night.

Fortunately, she recovered fully from the chemo brain, and has in fact been in full remission for more than two years now. Meanwhile my Lupron injections have ended but the residual low-T has had a drastic effect on my QOL.

You are fortunate to have recovered from your chemo brain so quickly, and may I presume also from the condition for which you were being treated?