ASCO 2019: Outcomes of Men with Recur... - Advanced Prostate...

Advanced Prostate Cancer

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ASCO 2019: Outcomes of Men with Recurrent M0 Prostate Cancer who Defer Androgen Deprivation Therapy until Metastasis

George71 profile image
George71

"This abstract retrospective reviews 2,636 men who had radical prostatectomy between 1981 and 2017 and then subsequently developed biochemically recurrent prostate cancer...

450 men who had been treated with prostatectomy and then followed after PSA recurrence WITHOUT therapy until metastasis, median follow up was 8.0 years and median metastasis-free survival was 10.0 years. The most predictive factors for metastases were Gleason score and PSA doubling time. This study examines the outcomes of men who deferred treatment until the development of metastases.

The median metastasis-free survival (MFS) was 21 years [without ADT] and median overall survival (OS) was 22 years. Age, Gleason score, and stage at the time of radical prostatectomy, and receipt of salvage radiation therapy [41%] were most associated with overall survival."

urotoday.com/conference-hig...

28 Replies

This is interesting! Thanks for the post!

George71 profile image
George71 in reply to tennis4life

I thought so too.

"In this retrospective study, patients with deferred androgen deprivation therapy for biochemical recurrence may live for decades before the development of metastases."

My feeling from the start has been that short-lived palliation should be deferred until needed.

Some men think that PCa follows a path to progression where the cells become increasingly aggressive. In fact, progression while on ADT is associated with treatment-induced changes that select for cells that are difficult to manage. Pre-ADT cells are not on the same path. I don't see how premature use of ADT can prolong survival.

I think that many men have rushed into ADT because they mistakenly feel that it is better to be treated than to wait. But ADT is not curative. &, of course, there are the QoL/morbidity issues.

-Patrick

TFBUNDY profile image
TFBUNDY in reply to pjoshea13

You speak my thoughts exactly.... I hope we are both right :-) I should ask my wife because she is ALWAYS right....

I am here for my husband who has a Gleason 9 prostate cancer treated with surgery ( good pathology except for EPE), and adjuvant radiation in 2014 at Hopkins. He is now in BCR (psa around 0.5) since this January. So he had a good run without ADT. At our appointment in April at Hopkins the oncologist was still discouraging systemic treatment saying that his prognosis without treatment is 5-10 years. We were wondering where that number came from and now see that it matches the results of this paper. Very interesting. Thank you for pointing it out. My husband had the PSMA - pet scan last Friday and we are anxiously waiting for the results.

George71 profile image
George71 in reply to FSB12

I agree completely with Dd7757's comment below --

many of the longest survivors are the ones that avoid ADT at all cost.

The more sensitive (PSMA scan and F18) tests find the mets years earlier -- and lead to early and possibly unnecessary treatment that leads to early castrate resistant PCa

GP24 profile image
GP24 in reply to George71

The guidelines are based on CT and bone scan for imaging. I think it is a mistake to apply these recommendations unmodified when using a more sensitive PSMA scan. Better follow the Australian guidelines and zap the mets :)

ncbi.nlm.nih.gov/pubmed/300...

ncbi.nlm.nih.gov/pubmed/311...

I think this will avoid early castrate resistant PCa.

George71 profile image
George71 in reply to GP24

I'm ok with surgery and or radiation of mets when they are found even when only visible with PSMA or F18 scans -- they can see them 6 or 8 years earlier than conventional scans -- but not accompanying radiation or surgery with ADT. The minute you are introduced to ADT even for a short time -- any surviving micro mets elsewhere in the body and the ones that survive the radiation in the treatment area will begin the morphing process toward castrate resistance ...

If you never go on ADT (until as a last resort) you can not become castrate resistant -- and castrate resistant is hardest to treat by far .

I have had 2 M D Anderson MOs and 1 radiation Onc. tell me ADT can not cure and does not extend your life. The RO said "ADT kills approximately 8% of the easy to control PC cells and when you add Zytiga they kill approximately 15%" -- they want to do it in combination with radiation because it makes the radiation more effective at killing cancer cells -- but the risk is not worth it if you ask me. As the article said, it can be 10 to 20 years for mets to appear without ADT --- my guess is with ADT it may not be as good. the average ADT trip to castrate resistant is 2 to 3 years.

And my last thought is the science is changing toward ADT --and Testosterone -- and the drug research is moving toward immuno therapy -- a lot can happen with drug breakthroughs in this day and age of medicine (on the dawn of immuno therapy / PARP / LU177 etc) -- Just slow the progression down enough and you will out last it -- even if they don't find a complete cure. As the article said -- even with PSA doubling time of 6 to 10 months it can take 10 to 20 years to metastasize and it could be another 10 from there.

GP24 profile image
GP24 in reply to George71

George, a combined treatment of ADT and salvage radiation works better than radiation alone. See this study:

cancertherapyadvisor.com/ho...

I would definitely choose this combination, you do not get a second chance to add ADT to your radiation treatment.

It is not the case that you have a fixed time of ADT efficacy, it depends if you have bone mets or had therapy of the primary tumor before. It also depends how low the testosterone level gets during the ADT treatment.

I have not yet seen a study that determined that adjuvant ADT reduces the efficacy of a continuous ADT a few years later. Trials that determined the efficacy of ADT accepted participants if the previous ADT had been terminated six months before entering the trial. So in that case they did not expect an influence on the ADT that should be tested in the trial.

The “ hit it hard and hit it early” paradigm has encouraged the early use of hormonal therapy which accelerates the time to castration resistance which is the beginning of the end. In 5 years , the pendulum will swing back to judiciously employing hormonal therapy based on PCA doubling time and the presence or absence of radiographic progression.

Unfortunately , at this time , many men are starting hormonal therapy too early, encountering all of the side effects, progressing to more toxic therapies , all with the hope of extending their life, for an unknown ,and perhaps insignificant , length of time.

As always, caution, depends on YOUR disease.

I was diagnosed in Jan 14 when the doctor doing my colonoscopy took the time to check my prostate (a recent PSA test was only 2.1).

I elected to do surgery, very successful, T2CNoMx, GS 4+4m ECE, Margins and Seminal Vesicles negative, only 10% prostate involvement, no incontinence and nerves spared. 18 months later...BCR. Started SRT in Mar 16 at .3, 90 days after completing that, PSA was .7, a month later 1.0!

Off to Mayo in Jan 17, PSA now 3.8. PSADT was less than 3 months, PSAV velocity, rapid! C11 Choline scan found four pelvic lymph nodes active, did 18 months of Lupron, six cycle of taxotere and 25 more radiation treatments.

Finished that treatment on May 18 with my last Lupron shot, T stayed at less than 7, PSA at less than .1.

In Oct 18 after the Lupron had cleared my system my T was 135 and PSA less than .1. In Feb 19 my T was 482 but labs showed PSA at .36! We repeated the labs on 16 Feb and it was .24, on 2 April .06 and now on 7 jun, .12.

So, given my clinical data, waiting for metastatic disease would not have been very long so aggressive early treatment fit MY disease.

This study said..."delayed androgen deprivation therapy (ADT) may be appropriate for carefully selected patients (Low Gleason score, limited life expectancy)... I was 57 when diagnosed and GS 8 so don't fit the requirements.

Kevin

Survivor1965 profile image
Survivor1965 in reply to Hawk56

I think your with Kwon

Hawk56 profile image
Hawk56 in reply to Survivor1965

Yep, liked his approach, rather than linear and sequential treatments, each destined to fail, combine treatments and bring them forward early in the disease, particularly in aggressive disease with the goal to overwhelm and produce longer progression free and overall survival.

Survivor1965 profile image
Survivor1965 in reply to Hawk56

I saw him for 4 years.we know each other very well. He hit me hard with treatments, said he was going to throw a nuclear bomb on a dandelion.

We moved to Phx so now with and Onc there. He is an amazing Dr and man. I was stage 4 mets everywhere and now, 5 years later, zero PSA and clean scans. I owe it to him.

All the best, Johnny

This is great! If for no other reason than it matches my bias against ADT. ADT was promoted at the time of my first consultation with a RO and continues to be promoted by the MO because of my risk profile of 0.2 cm positive margin and G8/G9 pathology. I am 76. I can live with a 10-20 year prognosis of not having metastatic disease. I can also take comfort from this report in the face of pretty strong urging from the MO that ADT + RT offers me a "significant advantage" over doing nothing or simple RT. He cannot specify what the advantage is. Right now, I am NOT biochemically recurrent and hope it stays that way.

I went and dug out an old dusty Encyclopedia Britannica and looked up the word "CONFUSING" and all it said was "Prostate Cancer".

Good Luck, Good Health and Good Humor.

j-o-h-n Tuesday 06/11/2019 5:37 PM DST

Hi George71,

I'd be very dead if I had not used ADT soon after diagnosis of Gleason 9 inoperable PG in 2009. I was advised to be examined at Psa 5 in October 2009, after having yearly Psa tests to avoid being diagnosed too late.

Psa was 6 by the time I got the biopsy in Dec 2009. Then attempted RP was in April 2010, Psa was 8.8, doubling time was speeding up, but fact was I had a large amount of Pca for a fairly low Psa, so in fact I'd been diagnosed about 4 years too late, and Pca had probably already spread. Its all too easy to be in this category. I tried to read that article you mentioned at

healthunlocked.com/api/redi...

It seemed to give the idea that most men will live about 20 years after diagnosis even with a gleason 9 so they die with the Pca, which is not the cause of their death.

Anyway, my docs would have disagreed with the general conclusions, and so far my many treatments have cost maybe $150,000, most funded by Medicare, and each time I paused the ADT the Psa just shot up, and I had to resume taking it. The initial attempted RP could not proceed because of too much Pca outside capsule and the later EBRT just tickled the cancer pink, and salvation RT hardly seemed to work, and Casodex, abiraterone gave average suppressions, chemo failed, and only Lu177 seems to have prevented quick progression to death.

In 2012, after quitting ADT and after having initial EBRT in a 2 year treatment plan, Psa went from 0.08 to 8.8 in 6 months, an increase of 110 times, with most of that in the 4 months when effects of Eligard ( ADT ) faded and my body began making normal level of testosterone.

It is important for men to never assume their Pca will not kill them, and well before the fancy - smancy graphs and statistics indicate !

So my docs know just how lethal my Pca would be if not treated, and its all very well for some to say I could have omitted most treatments and still reached the same overall survival time, but I think all that's BS, and if I had not continued with whatever treatment I could get after 2012, I'd have died by maybe 2015, after a horrible year of bone pains and other ghastly dysfunctions.

Tomorrow, when I talk to docs about results of the PsMa Ga68 scan I had yesterday, I'll find out if I need a 5th shot of Lu177, or some other treatment and maybe find out if there are a whole pile of other troubles coming in months, ahead.

It is now irrelevant for me to consider confusing conclusions of research about how long men last after diagnosis or how soon mets will occur after diagnosis, fact is that once diagnosed, my Psa doubling time reduced, ie, Pca progress speeded up alarmingly, and no man should rely on graphs of statistics to argue against having ADT, which I have found hardly any trouble at all because since 2010 to early this year I maintained fitness levels better than most men my age without any prostate troubles by cycling about 100,000km,ie, about 11,000km year, ie about 210km a week average, very regularly.

I have a hip with cancer mets in pelvis and femur near the joint, which has arthritis, stopping me doing things, including cycling and perhaps the EBRT I had way back in 2010 has caused rapid weakening of cartilage, because horizontal beams of EBRT pass through hip joints to get to PG.

But I am fully continent. But have total ED, and not worried about that because at 72, there's virtually now suitable ladies I could be with and all have had a menopause and aged more badly than I have. So partnering is just not on, so continuing ADT as a neutered male is not a problem at all.

So to me, ADT was very tolerable when I began it at age 62, no partner, so nobody to upset by getting sick.

There are regularly repeating postings online of a lot of stuff about Pca that has become irrelevant to me because I have reached the advanced stage where Pca is in my bones, and one report I read said that only 10% of men are alive 5 years after bone mets have been found by CT scan. I should be dead in 3 years.

But LU177 is changing that prediction, but I still have no idea how long I'll be well enough and pain free enough to talk to you all about having Pca. Most men just stop posting when they are in pain, and see the finish line coming up soon.

I hope you all have the best of luck, because those of use with aggressive Pca sure need luck.

Patrick Turner.

Hi I joined this group a couple of weeks ago. and I find it to be helpful. this article has got me thinking. I was dx in 2015 gleason 9 had a RP I was 53 at the time after about 6 months I did R . By 2017 my psa began to climb by the time it began to double every 3 months in spring of 2018 I started firmagon monthly injections for one year. I finished in April and now wait for progression does any one have any advice for me?

SeosamhM profile image
SeosamhM in reply to farm15

Look around this forum to educate yourself on options, Farm....but you also need to have a good medical team lined up....urologist and MO at a minimum... so that you have a plan in place and ready to go if PSA does increase ....what is your PSA now after the Firmagon?

Your MO will likely have several options for you if PSA continues to rise... Zytiga and Xtandi by example.... and you can look into Provenge prior to Zytiga .... and then radiochem like Xofligo and Lu177...

Hopefully, this course will take years for you (and me, frankly...I'm on Zytiga now...). In the meantime, lift a pint....all the while, of course, minding PJ O'Shea's sound nutritional advice! Cheers. - Joe M.

farm15 profile image
farm15 in reply to SeosamhM

Thank you!

farm15 profile image
farm15 in reply to SeosamhM

My psa is 0.06 and I understand it could stay for along time.

George..I feel it’s toooo complicated to generalize....for now...let’s hope we live long enough to feel the silver bullet hit the ravenous heart of the beast......👹

This is interesting. For my dad, the timing of ADT was 9 years after a prostatectomy. He had had a biochemical recurrence around the 6 year post prostatectomy but his urologist recommended no further treatment. It was only when a rise to 1.4 prompted his GP to refer him to an oncologist and a pmsa scan which showed a spinal Met that ADT commenced. Should he have started ADT and radiation years prior despite his urologists complacency? I don’t know.

This is a really tough decision. I have recurrent PCa, with a very low PSA of 0.54, and a doubling time of 16 months. So, I'm not in a hurry to start ADT or radiation until there is some indication of where the tumor(s) are. Yet, the moment my PSA increased from undetectable to 0.1 four years ago, an eminent radiation oncologist said I should start short term ADT and radiation "down there" immediately. My medical oncologist says my "disease is incurable, and all I can do is provide palliative care." He said I should be on Casodex. I think he meant all he and the Medicare Advantage HMO were willing to do was provide various sequential systemic chemical treatments. I saw another highly trained, experienced radiation oncologist this week as part of a F18 DCFPyL clinical trial, and he told me that regardless of the results of the scan, I should start radiation and ADT immediately. Well, I won't be able to claim they didn't warn me. Reminds me of the ol' saying that if you're a hammer, everything looks like a nail. I still want to try to find the cancer and get targeted treatment (radiation or surgery, as appropriate), if possible. If I can't do that by the time my PSA increases to about 1.0, I'll reconsider, while the chance of metastasis is still relatively low, even though I'm taking a risk that it could metastasize sooner. I have a great quality of life now, even with some side effects from the prostatectomy 7 years ago. At my age (76) and low PSA doubling time, the almost guaranteed side effects of ADT and/or radiation look like a worse option than potential metastasis. What I want out of life is a good quality of life!

FSB12 profile image
FSB12 in reply to ImaSurvivor1

Your personal plan of waiting till psa of 1 and getting a scan is exactly what my husband’s Hopkins doctors told him to do just this week. He has psa of 0.5 after having 0.44 and 0.35 in the last 4 months. He is post surgery and radiation (5.5 years) but no adt yet.

Yes George, what we forget is quality of life. My second LU177 treatment did not get all the mets & now they want castration & back on ADT before they will do another LU177 treatment here. It is hard to understand their motive, i just want to live a normal life for my daughters sake without beign drugged in a ADT coma.

mjbach profile image
mjbach in reply to ARIES29

Sorry to hear what you are going through Aries29 as I was hopeful LU177 would work for you.

My husband avoided ADT for the first 14 years with pCa. Eventually started ADT after mets to lungs.

His quality of life was great during those no ADT years compared to the last 4 with ADT but he will probably die of comorbidities which is the goal, I guess.

Hello mjbach, I had to look up that word comorbidities,which simply put..He will probably die of more than one on going problem & that is so true of all of us as we grow older.

I still will not take ADT & am enjoying what is left of life at 70yo with osteo arthritis & they say i can still work! Where is my question.

Anyway had a pet scan last week & showed no increase of the spot of cancer in my neck but could not view rest of body so will carry on with this business of living & paying for life itself.

My best Regards to all my fellow battlers with this desease & the carers we must not forget either.

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