2018 writeup on value of ADT, and whe... - Prostate Cancer N...

Prostate Cancer Network
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2018 writeup on value of ADT, and where it may increase mortality at 15 years!!

maley2711
maley2711

tcr.amegroups.com/article/v...

To date, I had not given any attention to use of ADT. Had only seen comments about its use as a palliative for metastatic cancer. So, I am eager to learn when and where ADT benefit may outweigh well publicized negative, even horrible, side effects. I don't like to provide my interpretation of an article like this....I provide so that the reader can reach his own conclusions...sometimes NOT mine!!

Hope this helps someone, besides me.

35 Replies
oldestnewest

That article is about combing ADT and radiation. Is that what you meant to post?

maley2711
maley2711 in reply to Tall_Allen

yes! I'm interested in the numbers for that combo....vs added SEs!!

Tall_Allen
Tall_Allen in reply to maley2711

Sorry, I'm not following you at all. Are you questioning whether long-term adjuvant ADT provides a survival benefit to primary radiation for localized PCa? If so, that has been proven for unfavorable risk patients.

maley2711
maley2711 in reply to Tall_Allen

I try to include links to source material, and allow each reader to decide for himself what the takeaway is from the studies/articles. My interpretations are always subject to correction, of course> I'll reread the material later tonite, and see if I can spot an error in my headline? Really, my purpose was for anyone interested to read the material...as there are a number of takeaways, not just what I headlined.

I sincerely apologize if my headline was in error!!

Tall_Allen
Tall_Allen in reply to maley2711

Several members here post unanalyzed source material - I don't see any value in that. But it's an open forum. You did, however draw a conclusion in your headline, but I don't understand what in that source material relates to yyour headline. I don't understand why you posted it. It's OK to say what you learned from it - maybe others will learn the same thing (or something completely different) if you alert us to exactly what it is you're seeing. Remember that ADT is used in several different situations - which situation are you refferring to? I'm just trying to make your post more clear..

maley2711
maley2711 in reply to Tall_Allen

Allen -

My conclusions would be no more than the conclusion cited in the article/study...though I might put an errant spin on the material> I thought my headline reflected one of the conclusions in the study, but perhaps I erred? As i believe I said, I'll reread later, and post correction if needed. I am talking about the scenari9s addressed by the materials...nothingmore, nothing less. Each to his own as to the value of individual posts...quite simple to click on a link , isn't it? I go to the trouble of posting links I believe might be of interest..and I appreciate when other men do that..but maybe you don't ...that's fine with me.

Tall_Allen
Tall_Allen in reply to maley2711

Again - I'm trying to understand exactly what led you to that headline.

maley2711
maley2711 in reply to Tall_Allen

Allen -

Would DECREASE mortality make more sense?

maley2711
maley2711 in reply to Tall_Allen

Allen -

Timotur replied " Maley: thanks for posting, confirms other things I'd read about ADT sensitizing cancer to radiation-- and thus the SoC for neoadjuvant ADT two months prior to radiation. "Though initially thought to be efficacious through cytoreduction and..."

Now you can see that different men are looking for different things here?

maley2711
maley2711 in reply to Tall_Allen

Allen -

This from the article, referenced in the headline.... " the 15-year follow-up suggested that in the subset of patients with moderate-to-severe comorbidities, the addition of ADT significantly increased overall mortality and cardiac mortality" I assume that there are many men with at least moderate comorbidities, so I believe the headline was relevant.

I still have not convinced myself that possible benefit of ADT outweighs the ADT SEs...from what I've read, very bad to horrrible SEs are almost guaranteed, and of course no guarantee of a benefit for any individual man...a probability of benefit, but not guaranteed.

I understand that this article is for radiation as primary treatment..isn't that clear in the article?

Good nite!!

6357axbz
6357axbz in reply to maley2711

You will find many here experience relatively minor side effects from ADT and live with them for years without serious impact to QOL.

Tall_Allen
Tall_Allen in reply to maley2711

The article is clearly about adjuvant ADT with radiation, but your posting didn't even mention it. This is a site for men with advanced prostate cancer, which means prostate cancer that has already metastasized. They are all on lifelong ADT (except for a few who think that dandelions will cure them). So your post is completely irrelevant for this forum.

I take it that you are trying to decide if temporary ADT is useful with the radiotherapy you are about to have to hopefully cure your prostate cancer. It is a good idea to fill in the profile with the details of your diagnosis. That way, I can point you to studies that are more relevant for you. The Prostate Cancer Network forum is more appropriate for you:

healthunlocked.com/prostate...

So your headline refers to men who have pre-existing conditions that will compromise their survival. If that is your case, you may want to fill in the following nomogram:

webcore.mskcc.org/survey/su...

NCCN prefers observation-only for unfavorable intermediate-risk men who have a life expectancy of less than 10 years. If you have been diagnosed as high-risk, they also allow observation as an option if your life expectancy is less than 5 years.

treedown
treedown in reply to Tall_Allen

Dandelions I love it. This is a clear reason why this forum is so great. Diverse views and in my opinion all are valuable. That said Dandelion greens are delicious I have them often in my salads but a cure, wouldn't that be awesome :) ?

maley2711
maley2711 in reply to Tall_Allen

Allen -

Having seen those 2 words many times, but never having actually understood, I checked last nite. From what I recall, isn't neoadjuvant "before" and " adjuvant "after" ? I read this " One example of neoadjuvant therapy is radiation therapy, which can be used to shrink a tumor before the patient undergoes surgery." So, I believe this article concerns neoadjuvant ADT, followed by radiation? and the radiation is the primary treatment.

This site says it is a place for men on AS, as well as advanced cancer. Most men on AS are interested in what they will do if a future biopsy is more concerning...or PSA starts marching higher.

Tall_Allen
Tall_Allen in reply to maley2711

That is strictly correct about neoadjuvant and adjuvant. Sometimes you will see the word "concurrent" to mean the ADT is continued during the radiation treatments. "Adjuvant" is used also to mean all 3. For example, the DART 01.05 GICOR trial was about the duration of adjuvant ADT in high risk and intermediate risk men. The "short term" adjuvant ADT arm was actually 2 months of neoadjuvant and 2 months of concurrent ADT. The "long-term" adjuvant ADT arm included that plus 24 months after EBRT was completed. "Adjuvant" ADT almost always includes 2 months neoadjuvant + 2 months concurrent - it is never started only after RT is completed. Yes, I know this is all confusing when you are new to it.

Malecare has a different site for AS:

healthunlocked.com/active-s...

The Advanced PC forum says:

About Advanced Prostate Cancer

A friendly prostate cancer support group where we can pick each other's brains. Our 24 hour online support group. Talking about advanced prostate cancer is a powerful tool. Our community is run by Malecare Cancer Support. We are men, fighting prostate cancer, together.

maley2711
maley2711 in reply to Tall_Allen

I feel like I'm in a lecture hall here??

Tall_Allen
Tall_Allen in reply to maley2711

Learning the jargon is part of the process, if you want to be an empowered patient.

maley2711
maley2711 in reply to Tall_Allen

healthunlocked.com/prostate... to be the same website for healthunlocked...the home page for prostate cancer

Don_1213
Don_1213 in reply to maley2711

That was about what I took away from the article. The rest of the article - ADT + radiation is better than radiation alone - that's accepted knowledge.

The cardiovascular issues ADT can cause are not widely talked about. Certainly none of my doctors warned about it before I started ADT. I'm heading this week to discuss "what next" with my cardiologist after an aortic CT scan this past week. I have seen estimates that 38% of men on ADT suffer some sort of cardiac problem, likely due to the ADT. That's not an insignificant number.

The other one I'm dealing with is dental. There have been several mentions of up to 80% of men on long-term ADT having bone/tooth related dental issues. Once I get clearance from my cardiologist I go in to have a fractured molar removed. Also had 3 root canals in the past 4 months.

Does that beg the question is ADT worth it? As a G9/10 I have to fall on the side of yes.. used with radiation it got PSA down to undetectable. Miserable side effects for me - but at least I'm here to complain about them. :)

maley2711
maley2711 in reply to Don_1213

Don -- Just from my sketchy memory......didn't the article show benefit for any age, and with other morbities, for all high risk men.....I guess that is your unwanted designation? I recall? that the exception for men >70 was for intermediate risk?

Of course, again, begs the question ....does some survival benefit outweigh the SEs?

How bad were yours?

Maley: thanks for posting, confirms other things I'd read about ADT sensitizing cancer to radiation-- and thus the SoC for neoadjuvant ADT two months prior to radiation.

"Though initially thought to be efficacious through cytoreduction and de-bulking of disease, there is a growing body of pre-clinical and clinical data to suggest that ADT and radiation therapy behave synergistically at the cellular level. Here, we have outlined the mechanism by which ADT results in down-regulation of AR-driven repair of DNA double-stranded breaks by the NHEJ pathway, hence serving as a radiation sensitizer."

What is interesting in this article is the breakdown of ADT duration for different stages, low, intermediate low/high, and advanced. A fine point, is that long-term ADT may not benefit overall survival for G-7 or below, but does benefit G8-10.

"To address the question of timing and duration of ADT for locally advanced prostate cancer, RTOG 92-02 was initiated. Patients were randomized to neoadjuvant short-term ADT (4 months goserelin plus flutamide) followed by radiation therapy alone versus long-term ADT, neoadjuvant ADT followed by an additional 24 months of goserelin, in combination with radiation therapy. At 10 years, long-term ADT improved all endpoints, compared to short-term ADT, including disease-free survival, disease-specific survival, local progression, distant metastases and biochemical failure—except overall survival. However, in subset analysis, patient with Gleason’s score 8–10 achieved an overall survival benefit (16).

Similarly, the EORTC 22863 conducted a phase III clinical trial evaluating the role of long-term ADT (1 month cyproterone, goserelin for 3 years) combined with definitive radiation therapy versus definitive radiation therapy alone in men with high-risk prostate cancer (T1–2, G3, N0–1;T 3–4, G1–3, N0–1). At 10 years, locoregional control, disease-free survival, overall survival, distant metastases-free survival and overall survival were all improved (17).

Together, RTOG 92-02 and EORTC 22863 demonstrated a clinically meaningful benefit of long-term ADT delivered concurrently with definitive radiation therapy for patients with locally advanced, high-risk disease, which remains the standard of care (18)."

maley2711
maley2711 in reply to timotur

Thanks Timotur! Apparently others here feel I shouldn't have posted this. I don't post things with any agenda in mind .....just pass along things, with hope they might be of benefit ...even to just one other man. I'm unofficially on AS, and this article was informative as far as deciding on any future treatment. Memorial SLOAN nomograms tell me that aman my age, in fairly decent health?, has a 6% probability of PCa death with a Gleason 3+4, if I do nothing. Surgery done at MSK would reduce that to 1% probability. worth the almost certain SEs of treatment for a man 72?? I'd like to see the same comparison should I evr be face with more advance situation.....I think Allen has suggested an MSK nomogram for that. I just posted the 8 nomograms I found earlier at the MSK site.

6357axbz
6357axbz in reply to maley2711

This site is for men with an incurable, metastatic cancer

timotur
timotur in reply to maley2711

Maley: knowledge is power, and I found it interesting to read the study above about the synergy between ADP and radiation since I went through the process last year. Anyway, it’s good to be one step ahead of the game, and know enough to be in the decision making process with your doctors. If you’re on AS, I would especially read the forums with patients in that category on HU’s PC forum, and the U.K. PC forums to learn from other’s about AS strategies. I didn’t look at the nomograms in determining a tx option because they are too general in nature to capture individual characteristics. Rather I focused on treatments for the stage t3b N1 SV I had, which pointed me towards radiation. I figured choose the best option, eat well and exercise, and things will take its course, and not worry about what the stats say.

maley2711
maley2711 in reply to timotur

Thanks! what specific tests were used, I assume after biopsy, to determine that exact stage you cite?

I understand your comment about statistics.....nevertheless, knowing the potential and probably side effects from various treatment options......and looking at 10-15 yr mortality results, what is your comment about 1% PCa mortality probability with treatment versus 6% PCa mortality probability with no treatment during the same time spans? That is for a healthy man......with significant comorbidities , the differenc e would be even less?

I ask because you seem very astute about all of this!

timotur
timotur in reply to maley2711

Just my opinion, don’t get too caught up in statistics of that smallish degree for planning purposes, try to look at the big picture, and make a plan according to the specifics of your disease. AS needs to be managed carefully with imaging and blood tests. Just at a basic level, you should be monitoring PSA and free-PSA, and be aware of doubling-time and %f-PSA that would trigger another biopsy, or an advanced test like the 4K Score or PHI test. Likewise for imaging, probably need a yearly mpMRI to keep an eye on progression. Then, start researching options for treatment of Stage 1 or 2 in case the tumor does progress. Lots of options to consider. Keep reading and learning, especially those forums I mentioned. Armed with those facts talk with your Dr about tx vs AS. You can’t make this decision with a nomogram. For the most part, this forum is a good resource, but is beyond what you should be concerned with IMO, in other words, don’t look too far forward.

maley2711
maley2711 in reply to timotur

Thanks Timotur. It's interesting in the ways we write things that we believe will be clearly understood by others, but not always the case, at least for me. For example I mentioned comparing 2 numbers, 6% for do nothing forever, and 1% for treatment now.

You answered that I should avoid being too concerned of statistics of that smallish degree.. to clarify for me, do you mean that you view the additional 5% PCa mortality as too smallish to warrant any consideration of treatment until testing might show a larger mortality risk? In a perfect world with no treatment risk/SEs, of course we'd want the reduced PCa mortality risk, but the probable small reduced PCa mortality conferred by the treatment doesn't warrant taking on the risks of treatment?

Thanks Timotur!

timotur
timotur in reply to maley2711

The 5% benefit is a statistical average of those observed in the study, and you may be above or below that number. So I wouldn't depend on that number alone to make a decision about whether to do treatment.

Also consider the net benefit by weighing the risk of SE's from a chosen treatment option (IC, ED). Is the risk of those SE's worth it for an inferred statistical gain of 5%? The SE's aren't reflected in the nomogram, and could have a huge effect on your QoL. Also it doesn't consider the effects of diet and exercise, which may slow progression of PCa.

maley2711
maley2711 in reply to timotur

Thanks Tim ......I was asking that, assuming we believed the 1% and 6% numbers as accurate probabilities, what YOUR view is on the decision to treat or not.....ie how you view the treatment risks vs the possible benefit?

BTW, my other question was.....in arriving at the detailed stage T........... that you mentioned initially,what diagnostic tests did you undergo pre-treatment to arrive at that stage designation.?

timotur
timotur in reply to maley2711

To me personally, a 5% difference is in the "noise", i.e. not significant enough to outweigh other considerations of age, treatment choice, and SE's. Myself in your shoes, I would try to stay on AS as long as possible and try to slow progression through diet, supplements, and exercise. I would eliminate red meat and milk from my diet, and have a very active lifestyle. AS takes close monitoring though, and a PSA test every three months and a yearly mpMRI would be in order. That's my opinion only, your doctor may say you don't want to be the guy on AS who's PSA shoots up and your tumor invades the capsule. It comes down to a personal decision about risk vs reward.

The two tests for me that indicated a biopsy was needed: 1) a free-PSA test result of 3% (cutoff <10%) and a 4K Score of 77% (cutoff >15%). The 4K Score tests gives the chance of a GL-7 or higher tumor. I would do these to give you more information.

maley2711
maley2711 in reply to timotur

Thanks Tim!!!! exercise....well at least try to walk 45 minutes/day. diet......hmmm, not sure if I am willing to change too much..kudos to those who do so......are there any credible studies. Supplements...know little about that...I'd need to see some studies. OMG...more research!!

I do eat maybe 1/3rd pound chicken, fish, beef or pork......1/2 gal mlk, plus some cheese in weekly 1-2 omelettes. and I eat 2 very small sweet treats each day?

Beans and me don't agree..if you know what I mean!! Love burritos...but try to limit one/week.

Meanwhile, apparently the odds od dying from some other cancer or cardiovascular seem to be very high.....no matter what i do, I'm a dead man anyway...chuckle??? I feel so badly for all the bad stuff others are experiencng/experienced.....and of course naturally terifies me as to my possible future. ...with or without treatment.

Woah, lots of info and more info.

Yes I’m in the Cardiology plagued issues APC S4 metastatic mode male.

S.E.’s I’ve had minimal if just a few, maybe. Warm flashes ok live with em.

Not a bad comprise to Cancer spreading.

Cardiovascular issues: I’ve just had an RF Cath Ablation May 6th to correct my persistent (Constant) AFIB. Isn’t NSR sinus rhythm wonderful!

Yes, I’m on XARELTO max dose 20mg for the rest of my life; protectant for possible AFIB return blood clots and cancer causing blood clots.

Yes, I’ve just got Transferred to a great Cardiologist Interventionist vascular medicine doctor that knows clotting blood very well.

My CT&NM scans 06/08 showed no metastatic detectable cancer anywhere on those two scans.

My PSA 03/10 was 1.032 and June 08 dropped to 0.750.

I’ll keep take ingesting my

1. Abiraterone 250mg daily

2. Prednisone 5mg 2X daily

3. Lupron 90 day injections

ADT SE’s are not bad at all!

But not gonna rely on my love of Skinny Popcorn Aged White Cheddar to slow or contain my APCancer return!!!🍿🍿🍿

I’m off to exercising phase 2.

Good day.

Doug

timotur
timotur in reply to depotdoug

Congrats on the lower PSA Doug, and hopefully your AFIB is under control. You’ve got a full plate of ADT, good that you are exercising to manage the SE’s. Ah, yeah popcorn, used to love it back before dx, traded one PC for another. 😀

I know I'm losing it and am a little bit psycho but I believe I am in the Prostate Cancer Network site and not the Advanced Site right now? Am I not?

fluffy -

Perhaps you read the comment from another participant, who suggested that I shouldn't post here on anything pre-treatment. However, other men thanked me for what I posted!! On Healthunlocked, I receive email updates and sometimes click on something of interest....regardless of pre or post treatment. No one forces anyone to read a post that is not of interest to them. So Fluffy, I think you're fine to continue here...mostly friendly folks!!

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