Testosterone Recovery During Intermittent ADT

[MateoBeach]

It appears well established now that, in general for APC, intermittent ADT (IADT), or "taking breaks" from ADT drugs is "not inferior" to continuous androgen deprivation (CADT).

pubmed.ncbi.nlm.nih.gov/263...

And protocols for the timing of starting and stopping such ADT breaks are being refined.

pubmed.ncbi.nlm.nih.gov/315...

However, from what I have found, in none of the studies did they monitor and stratify men for their testosterone recovery during the time off of ADT. This is surprising since the whole reason for doing IADT is to allow some period of testosterone recovery to normal, or at least physiologically beneficial levels.

If the whole idea of intermittent ADT is to have some period of recovered testosterone, which does have significant benefits for the body as well as QOL, then that should be considered. Some men recover T production within a few months, but many not until a year or perhaps never. So to even-the-playing-field for those who do not recover T production while on break, it is reasonable to consider physiologic (normal levels) of testosterone replacement (TRT) during this time, as long as normal monitoring of PSA and scans continue.

Earlier this year, I was researching this topic to argue for intermittent testosterone replacement for myself for my severe sarcopenia (loss of muscle mass that resulted in a collapsed vertebra and spinal nerve compression, and severe hypogonadal symptoms ranging far beyond fatigue, hot flushes and loss of libido. I encountered three different experienced urologic oncologists who raised this same point, suggesting testosterone replacement should be considered not different from normal testicular recovery of T production.

You would have to argue this with many MOs who may not take this into consideration. My sarcopenia (body muscle wasting) and hypogonadal symptoms have improved wonderfully from just a few months of testosterone replacement this year.

[Tall_Allen]

Nothing about iADT vs cADT is well established, The starting PSA, PSA response to ADT, and the detected presence of distant metastases seem to have some effect on outcome. So younger men who are recurrent or only locally advanced, have low PSA pre-ADT, respond nearly completely to ADT may find iADT beneficial; while older men with distant metastases, very high initial PSA, and incomplete response to ADT may be better off sticking with continuous ADT. Here's a good review--as you can see, outcomes are all over the place:

sciencedirect.com/science/a...

I agree that T recovery should be monitored, and it certainly is in most studies, but it is more important to monitor patient perceptions of QOL. One patient might feel just fine with low T, while another might not feel restored until his T is quite high. The T that contributes to a patient's QOL is very individual. In general, most studies have found a very subtle QOL improvement with iADT.

Because the data are equivocal, patient preference should guide decision making.

[MateoBeach in reply to Tall_Allen]

👍🏼

[Magnus1964 in reply to MateoBeach]

TA is correct, there are some omissions in the PubMed articles. The data used is somewhat out dated, and there is no mention of advanced disease with distant mets. I would not put much stock in these studies.

[Hidden in reply to Magnus1964]

Are there reliable studies on intermittent vs. continuous therapy or studies ongoing?

[Magnus1964 in reply to Hidden]

There are no studies that I am aware of, or at least that I would put much trust in. I have been dealing with ADT drugs for nearly 20 years. My problem with intermittent ADT treatment is, "are you giving any new lines of cancer cells a chance to find a work-around for the drug."

[Schwah in reply to Tall_Allen]

Was that a typo TA? When you say “…older men with distant metastases, very high initial ADT…”, don’t you mean “..very high initial PSA..”?

Thx

Schwah

[Tall_Allen in reply to Schwah]

Yes - thanks! I'll correct it.

[Jbooml in reply to Tall_Allen]

That said, would it be helpful for many of us to try a vacation to determine our T recovery ( or lack thereof). I ask in reference to the suggestion some never recovering T at all. Why continue flogging the horse with ADT if it’s stiff with rigor.

[Hidden in reply to Jbooml]

That's my question. If you are castrate without anything, why is ADT even necessary?

[maley2711 in reply to Hidden]

such as with ochiectomy????

[Tall_Allen in reply to Jbooml]

You can know if T starts rising pretty quickly after the expiration of your last shot. And you are right that the longer you've been taking shots, the longer it will take to recover completely. Now, with Orgovyx, it only reduces T while taking the pills. But who knows after 10 years of taking pills?

[Saydeebugz in reply to Tall_Allen]

Tall-Allen... THANK YOU for posting this particular response mentioning Orgovyx oral treatment!!! After the passing of my husband (who was a 2x PC survivor but taken away by a massive heart attack),I am left alone to take care of my 92yr old father. Dad has been in the "watch mode" for MANY yrs. Now due to his latest PSA test (2nd one after a Urolift 6mos ago) went from 8 to 13 (T at 900 and NO OTHER symptoms) the Dr (urologist) wants him to start Lupron injections ASAP. We've decided to pump the brakes on that as Dad's QOL is paramount and I KNOW what's coming after the Lupron and I fear Dad will suffer greatly just from side effects. I will read up on this oral med to see IF that is an option.

[Tall_Allen in reply to Saydeebugz]

I'm not Catholic, but you come as close to a saint as any I've seen.

[Saydeebugz in reply to Tall_Allen]

WOW, a Saint... I've certainly been called much worse in my life!!! Not too sure about Saint, I just take the best care I can of those I love as nobody else is going to do it. I want you to know that THIS site/group has,and continues to, help me do the best that I can. Thank you for all that you do!!!

[Karmaji in reply to Tall_Allen]

Thanks for the reference..May be you give your opinion regarding iADT for my case

psa in may 2019. 30 gl 8

T3bnom1..two tiny spots on pelvis..with choline scan

oligo metastasis

Went on adt july 2019 and RT in nov 2019....

PSA <0.006 since oct 2020...

have good QOL so far

Having following 5 point therapy during remission...

adapted nutrition

exercise at least 1 hr walking uphill in nature

intermittent fasting 14 hrs

mindfulness...i am not the body

=======

sould I try iadt after 3 years..

right now I am having 4 months

injection instead of 3 months in agreement with my onco....

I may try 5 month lapse...

Thanks for reading...

[Tall_Allen in reply to Karmaji]

If ADT is bothering you, a vacation may help you.

[Karmaji in reply to Tall_Allen]

No it does not bother me at all....I read it may make mind foggy or some lapse of memory which I feel...

Sure I can develop new neuron circuits...neurogenesis...excellent book by Brant cortright

Still which markers are there to say if it is useful...

Why to take it if it is not required....because low T levels are not human

During remission, we need holistic therapies besides chemical drugs

Thanks for your compassionate attention as ever....

[maley2711]

Mateo -

It sounds as if you are certain the T lowering from ADT is the cause of your severe sarcopenia, as symptoms alleviated with T replacement. another strike against ADT for someone considering radiation + ADT for 18 months! That must have been a dreadful experience " collapsed vertebra and spinal nerve compression" ugh!!

[MateoBeach in reply to maley2711]

True. However taking short term ADT with and after radiation is worth the sacrifice to get the maximum benefit from the RT. Though 18 months does not sound so short term! For some, especially if PSA is low, perhaps six months is sufficient. It is a murky area.

[maley2711 in reply to MateoBeach]

Thanks Mateo. Have you seen any data at all re duration of ADT and PSA starting level? I had 1 mm (10% of one core) of 4+5 found in a total if 12 standard cores and 6 targeted cores.....a 2nd core was 10% 3+3, and all others, including all targetted cores, were benign. Kaiser urologist(20-25 years experience) said this low volume 4+5 finding was highly unusual in his practice......he was willing/volunteered to monitor my PSA at almost 73 years of age, but of course Kaiser's tumor review board advise only surgery or radiation, no monitoring.

My PSA, last checked 1-2 months ago, has been stable at 7.5 since January 2019. A newly found smaller PIRADS 3 area did show up on my 2nd MRI done just a month ago subsequent to diagnostic biopsy of earlier detected PIRADS 5(all cores benign).

I'm an "analysis paralysis guy", so this is very difficult decision of course.....whichever way a man goes, QOL is going to suffer, perhaps horribly....though seems addition of a 18 mo ADT to radiation might make the radiation option a higher QOL risk compared to surgery???

I had previously decided I'd take the risks of radiation, but that was before 4+5 was found and ADT added to radiation!

[MateoBeach in reply to maley2711]

Surgery vs. Radiation as primary therapy is always a difficult decision. The advantage for surgery (RARP) is that you would have much more information on the pathology. You would get that outlier 5+4 clarified. Perhaps you are really 3+3 and will live without ADT to 100! You will also find out about capsule penetration, seminal vesicles and have some nodes sampled. All good info you do not get with RT.Radiation is easier at the start but becomes very difficult with side effects to the bladder and rectum as well as sexual nerves. So I would not let that dissuade me.

You do not need adjuvant ADT with surgery. That is the way I would personally go in your situation. It demands clarification. And you DO have prostate cancer, so may as well get rid of that thing in one stroke. But it is a personal decision.

[maley2711 in reply to MateoBeach]

Thank you Mateo for your cogent points.....you hit many/most of the points i have been debating with myself. It would be great if I could get the urologist aand RO in the same room for a 1 hr discussion of my questions..... I'd probably walk out with a decision made..sadly, not the way the system works? My urologist did not initially suggest I consult with RO...I asked for the referral. AT the end of 90 + minute consult with RO, former prof at U chicago, he walked me to the door(clinic was closed by then). As I stepped out, I said that it is such a tough decision, concerned about ADT mainly.......his reply that he thought I shouldn't rule out surgery...that in the past surgery not even considered for men 70+, but the trend is that more and more men 70+ are deciding on surgery... I failed to ask which he would choose with my identical diagnostics and age? would an RO admit he would choose surgery? ora Uro that he would choose radiation? I should have asked!!

his RO is the lead SBRT guy at Kaiser here..but he wouldn't offer for high risk, no matter the studies that have shown good results. In general, NCCN does not yet advise for high risk.

So, I'm balancing general risks of surgery for older man, higher surgery risks of long-term incontinence ,higher rates of salvage for surgery, etc versus the list of risks for both radiation and 18 mo ADT. also, there is no slam dunk salvage for radiation comparable to go -to radiation salvage after surgery....which may account for the observed lower rates of salvage(except ADT) for primary radiation treatment.......sorry, talking to myself!!

[MateoBeach in reply to maley2711]

If you needed salvage after surgery, say if your Gleason was upgraded and you later had BCR, then you could do salvage RT. But if you have RT as primary treatment you cannot do surgery for salvage, nor re-treat over the same field. Burned bridge.

[maley2711 in reply to MateoBeach]

Yes, only less common salvage treatments for radiation. One of the large retrospective comparative studies I just reviewed showed 5 and 10 yr outcomes for modern radiation + ADT compared to surgery mostly without adjuvant treatment. Long-term 10 yr results mostly the same.....believe radiation had very slight edge, but not at all decisive. What was interesting was the documentation for salvage.......MUCH MUCH higher numbers (40%?) for surgery, yet long-term results were about equal. Of course , with radiation, one could argue the salvage, ADT, is part of initial treatment. greatest part of surgery salvage is , of course, radiation +/- ADT. Nowadays, they probably want to include ADT with salvage radiation. So, the contrary argument is........with surgery, agreat many men, especially my Gleason 4+5, will suffer the consequences of 3 treatments, and radiation side effects are ven worse when used as salvage...seems to be documented. I guess with initial radiation, salvage is HIFU, brachy , cryotherapy.

Each time I try to sort thru all this for my individual diagnosis, find some other angle to investigate!! It may be a coin toss.......or not? Someday with improved patient records, big data will hopefully be able to be of more help. As it is, I'd guess average busy Uro or RO really has no time needed to do this properly. Really need a full-time data driven professional to be guiding patients. who knows when/if that will ever happen? The local med school here touts there cancer nurse navigators...but I doubt they are especially detailed data driven in advising patients.

Just got a reminder to schedule a followup appontment with Uro..guess I could throw this problem onto his lap. I have learned that even a 3% probability is not to be ignored......that was the approximate probability of my PSA driven biopsy resulting in high risk PCa diagnosis!! Then with my PIRADS 5, 0nly 10-20% probability of no cancer being found...lo and behold, no cancer found in PIRADS 5. Then there was only 5-10% probability of signifivcant cancer being found in some area not included in the MRI index lesion...lo and behold, 4+5 found in one of the standard non-targeted cores. So, I take very seriously these supposed low probability negative consequences of various treatment modalities. I guess it is up to patient to demand that various specialties seriously engage in side effects discussion.......my nitial talks with uro and RO only vaguely touched on the topic....par for the curse I suppose!

[London441]

Is there aspect of your sarcopenia that prevents you from exercising?

[Hidden in reply to London441]

Sounds like he is convinced it caused spinal compression, which likely makes workouts painful

[London441 in reply to Hidden]

Maybe. If he never worked out to begin with and continued that on ADT then it wouldn’t surprise me at all.

There are obviously situations where a short period of rest is necessary, but subsequently we need movement to successfully cope with injury.

A couple of mistakes men commonly make on ADT are

1. Initiate it in a sedentary condition, and

2. To depend on stopping ADT alone to release them from side effects. It is a fool’s errand for a number of reasons.

Exercise is critical to both preventing and solving low T issues. Exercise and caloric restriction are also very underrated in assisting T recovery.

Return of T is never assured anyway, and in many cases is flat out unlikely.

[MateoBeach in reply to London441]

Not at all! It took two surgeries to decompress it then three months progressive rehab. By six months I backpacked a week in the high country of Yosemite with my wife. I lift weights 2-3 times per week. But I no longer do the heaviest weights for dead lifts and squats: 90-100 pounds instead of 250-300, to protect my other vertebrae. Tomorrow leaving for 10 days backpacking in the Sawtooth range of Idaho. No residual pain even carrying a full pack up and down mountain passes. Life is good!

[Hidden in reply to MateoBeach]

Great news a! Now go forth and frolic . Luv ya man! Enjoy the sawtooths! Send us pic please? Safe travels!

[Balsam01]

Wasn't a theory of IADT to try and delay castration resistance?

[treedown in reply to Balsam01]

I thought so and it would seem the most important if that is the case. Wouldn't it?

[6357axbz in reply to Balsam01]

The following link should take you to the article about the origins of that theory.

wired.com/story/cancer-trea...

It’s attributed to Dr. Robert Gatenby (Moffitt Cancer Center)

[Balsam01 in reply to 6357axbz]

This is a great article! Thanks for sharing!

[6357axbz in reply to Balsam01]

Interestingly, in Gatenby’s trial of one, he kept the patient on continuous ADT (Lupron I think) but the zytiga was intermittent

[Spyder54 in reply to 6357axbz]

Fascinating article. Allowing the more resistant PCa cells to be overrun by the more ADT Sensitive cells through a carefully monitored ADT stop/start (BAT) approach going back to survival of the fittest (Darwin). This as a contrast of trying to wipe out everything knowing the Resistant cells will eventually win, and we, the patient, unfortunately lose. Kind of makes sense. I still hope to find a way to kill all the PCa bastards with all approaches known. So far, that seldom works for most stage 4 cases. Hmmmm…

[Break60]

I have my T measured every time I get a psa test . When I went on vacation my T never increased above the 70s . I did feel better though.

[westof in reply to Break60]

Stopped Lupron 7/20 and tapered off Z&P in January 2021. In May my T was 115 and dropped to 105 in August.

I do feel better, just continue to monitor...

Turn 73 in December.

Best

[Hidden]

Anyone like me in hypogonadism , osteopenia and way past sarcopenia dreams of t again ! Good for you! Doing it “ your “ way .. ❤️✌️

[Puckcancer]

I did intermittent and when PSA reached 10 I would get another shot. I did it for about 2 years until PSA was raising faster.

[j-o-h-n]

I got my T back by way of big TITS......

Good Luck, Good Health and Good Humor.

j-o-h-n Monday 09/06/2021 10:05 PM DST

[Jbooml in reply to j-o-h-n]

Speaking of daddies best friends…..I haven’t suffered in sympathy so to speak after all my ADT…puzzles me that I’m still a mostly typical b cup 60 something. Could it be that the tittie response to ADT can be deferred with age. No..don’t ask..I’m not going to post pics.

[j-o-h-n in reply to Jbooml]

Tracing will suffice.....

Good Luck, Good Health and Good Humor.

j-o-h-n Wednesday 09/08/2021 5:25 PM DST

[lewicki]

I am seriously considering High T. It seems the cancer that shows on a PSMA and Auxumin seem to be dormant or unable to replicate. Waiting for PSA to start going up.