High Gleason low PSA - quit ADT?

[Purple-Bike]

Diagnosed with Gleason 9, PSA 1.7 two months ago and adding to the replies to GabF:s post a day ago on the issue:

"Androgen deprivation therapy (ADT) might not improve survival of low-PSA, high-grade PCa, according to the investigators. For other men with Gleason 8 to 10 tumors treated with external beam radiation therapy, ADT appeared to increase survival: ADT was associated with 13% decreased risk of death from any cause when PSA values were above 2.5 ng/mL. For low-PSA, high-grade PCa patients, however, the risk of all-cause mortality increased by 36% with ADT...........

standard treatment for high-risk prostate cancer consists of radiation with long-course ADT. However, low-PSA, high-grade disease appears to be potentially resistant to hormone therapy."

from Yang DD, Mahal BAV, Sweeney C, Trinh QD, Feng FYC, Nguyen PL. Identification of low prostate-specific antigen, high Gleason prostate cancer as a unique hormone-resistant entity with poor survival: A contemporary analysis of 640,000 patients. 2017 ASCO Annual Meeting. J Clin Oncol 35, 2017 (suppl; abstr 5080). Poster

Besides having EBRT and brachotherapy, I am on ADT (Firmagon and Bicalutamid). Given the above apparently negative impact of ADT, does anyone have any idea whether I should consider replacing or complementing my ADT with systemic therapy?

One idea for this question arises from a post by Tall Allen, although it was not directed at low PSA. Quoting from his post: "Systemic therapies - chemo, Zytiga, Xtandi, Erleada - increases time to castration resistance and prostate cancer survival in the newly diagnosed".

My doc said the quoted study is flawed in its design and with lower levels of ADT than is now given. After five weeks of ADT and EBRT, my PSA is down to 0.14 and he says this shows my cancer is not resistant to ADT and that I should continue with this.

[Shooter1]

Up, down and sideways. You are getting good results so far, I am staying with it (well really no choice as I hac orchiectomy), Push it a little farther. Your PSA will probably drop farther., Good luck whatever you choose.

[LearnAll]

Almost ALL prostate tumors have both Androgen sensitive as well as Androgen resistant Cells. Its the proportion which is important. If you have cells which do not produce PSA or produces little bit...It shows that you MIGHT have an aggressive variant of Prostate Cancer.To find out if you truly have an aggressive variant, you will have to know....

(1) Do you have Lytic type bone lesions seen on X ray or CT or MRI scan

(2) Do you have visceral Mets?

(3)Do you have lymph nodes bigger than 5 cm.

(4)Does your biopsy say you have higher than 4+4=8 Gleason Grade ?

(5) Are your NE Markers elevated ? These are serum Cromogranin A, Lactate Dehydrogenase, Synaptophysin and Neuron Specific Enolase.

(6) Do you have serum Calcium levels higher than 10.5 ?

(7) Is your Serum Carcino Embronic Antigen (CEA) elevated ?

(8) Does your germline testing show presence of BRCA1 or BRCA 2 mutations?

Out of these 8 tests, If you have 5 tests positive, your chances of having an aggressive variant is very high (over90%) Give yourself 10 marks for each question, and that gives of your chances of aggressive variant...more than 50 points: positively Aggressive Variant.

As I always say...Know the bird first.. Is yours a dove or a vulture or may be Dolture ? Find out first so you can decide if you need a hand gun or a machine gun to kill it.

Note: There is silver lining in that your Nadir PSA has reached 0.14 ...which means lots of your cancer cells are androgen dependent...hence can be killed with ADT.

[Purple-Bike in reply to LearnAll]

Thanks, LearnAll.

I don't have answers to all of those questions, and I have none of the biomarkers of point 5. If I choose one to be a biomarker as a complement to PSA, do you know if Cromogranin A is likely to be the best one? I understand that ptostate cancers that secrete chromogranin A are often resistant to anti-androgen therapy.

As for my PSA being down to as low as 0.14, and given that it was only 1.7 at diagnosis, could this mean that the cancer has been androgen dependent, but may in large part no longer be so?

[LearnAll in reply to Purple-Bike]

The fact that androgen deprivation got your PSA to 0.14 itself declares that most of your cancer cells were androgen dependent...otherwise why they got killed when you turned the androgen tap off.Besides PSA, you can follow two simple biomarkers...(1) Bone Alk Phosphatase (2) Lactate Dehydrogenase. They are not expensive. If you see any of them trending up..then more needs to be done..otherwise you should be fine.

[Purple-Bike in reply to LearnAll]

This is so valuable, thank you.

I have read your posts on Bone alkaline phosphatase.

Do you think a test for ALP-2 could tell if I have mets in the bones now? I have confirmed mets in the lymph nodes, but suspected not confirmed mets in bones. Have been on ADT for six weeks now. Doc says he will only know if there are Mets in the bones in April, with PSMA after 6 months of ADT. No ALP test taken.

If a test is taken now and shows elevated level, is this a sure sign that there are mets, with the elevated level showing release of the enzyme into the blood caused both by the cancer and by the ADT killing the cancer?

[LearnAll in reply to Purple-Bike]

If you have already completed 12 weeks on ADT, then your initial PSA and ALP bounce effect is gone. Biomarkers can tell a lot about bone mets...they change even before your regular scans start showing bone mets. You need to check TWO biomarkers..(1) Bone Specific Alkaline Phosphatase

(2) Urinary Collagen cross linked Telopeptide (NTX). (indirectly tells how much bone is damaged and needs repairing )Bone ALP tells you how much bone is being repaired

Whereas Urinary NTX level tells you how much bone is getting damaged by directly measuring fragments of proteins caused by bone loss.

If you have active bone mets, both the above biomarkers will be elevated. Dead or healed bone mets might show on bone scan . Gets confusing without matching biomarker levels...as biomarkers only indicate active , alive bone mets

If both above tests come in low normal range. .you can be re-assured that there are hardly any active bone mets.

I routinely (every 2 months )check these bone biomarkers and keep a chart about their trend.

[Purple-Bike in reply to LearnAll]

Are bone mets still active - and show elevated bone ALP and urinary NTX levels - when under ADT?

I have only had six weeks of ADT, not 12.

Thanks again!

[LearnAll in reply to Purple-Bike]

You need to wait until 12 weeks after starting ADT. Because until 12 weeks you are in the period where there is false elevation of PSA and Bone ALP. When Cancer cells are dying, a bunch of PSA and BALP is thrown in blood by dying or dead cancer cells ..giving a false reading.After 12 weeks, you should check biomarkers to get correct picture.

[Purple-Bike in reply to LearnAll]

But that is what I need to see! I only have suspected not confirmed mets in my bones. IF there are mets and a bunch of B ALP is thrown into the blood I will know I have mets and can start the extra treatment needed for that.Otherwise I will have to wait until April to find out if I have mets in the bones. Only then will PSMA show this.

[Purple-Bike in reply to LearnAll]

LearnAll, does what I wrote make sense? Using a Bone ALP to indicate whether the suspected, not yet confirmed, mets in the bones are indeed metastases?

[mperloe in reply to Purple-Bike]

GA68 dotatae or FDG PET can detect neuroendocrine tumor type.

[Hidden]

I agree with your doctor, (In my strictly amateur opinion.)

[Tall_Allen]

I think you are misinterpreting that observational, retrospective study. It was not a randomized clinical trial among men with low PSA subtypes where some men were given ADT and some were not. It only shows that the low PSA subtype has poorer outcomes and doesn't respond as well to normal ADT. It argues for the opposite of your conclusion - treatment intensification, rather than less ADT.

It adds little to use bicalutamide with Firmagon - if you want to go more intense, add Zytiga or Xtandi or docetaxel or docetaxel with carboplatin.

I would also recommend you biopsy one of those metastases. If IHC analysis shows low AR expression, you may have a subtype known as "double negative." There are clinical trials for that IHC may also quantify the expression of PSMA, which may allow you to take advantage of any of several targeted therapies in clinical trials. Genomic analysis may reveal a somatic BRCA mutation (I assume you've already had a germline test), which may respond to a PARP inhibitor.

[Purple-Bike in reply to Tall_Allen]

Thank you! I hope I am not overwhelming you with my response.....

I can't now find the post or article with your quote about systemic therapies increasing PC survival in the newly diagnosed and I don't recall the context. .What I find from your great PSA article makes me wonder if it concerns only those with confirmed metastasis; there the virtue of systemic therapies reflects studies on metastatic PC.

I only have confirmed metastasis in my lymph nodes in the pelvis. The PSMA and NaF - PET show suspected mets in four spots in the spine ribs plus one spot in the iliac bone, with my doc estimating the risk at 50 %; the spots are such that he cannot be sure. He says we will only know in April, with a new PSMA when I have been on ADT for six months.

Do you know if there is reason to believe added systemic therapy would be beneficial in a case like mine, Gleason 9 with only confirmed mets in lymph nodes?

Two of the 16 tissue samples from the biopsy in the prostate showed intraductal cancer IDC. Perhaps that's what's causing my low P SA. and not a double negative.

In any case, I suppose a biopsy of a met in a lymph node is not easily done....

I have not done any germ line testing, since there is no history at all of prostate cancer in my extended family.

[cesces in reply to Purple-Bike]

It would seem your doc and Tall Allen are at odds.

If I were a betting man, I would bet on Tall Allen.

The only good solution is to take written copies of your Doc's speculations and Tall Allen's speculations and get several second opinions.

Then report back here with what you learn.

May I ask geographically where you are located?

[Purple-Bike in reply to cesces]

Actually I have a hunch my doc may go for Tall Allen's suggestion if I present it - I am busy reading up on the issue. I am staying in Finland but will be back home in Stockholm, Sweden, by Xmas. Are you in the relative proximity?

[cesces in reply to Purple-Bike]

I don't know any Docs in your area of the woods. I am better in the USA.

[Tall_Allen in reply to Purple-Bike]

Here's the article about newly diagnosed mHSPC:prostatecancer.news/2017/06...

"if it concerns only those with confirmed metastasis; there the virtue of systemic therapies reflects studies on metastatic PC."

You are right that almost all the research we have is about metastases detected with a bone scan/CT.

"The PSMA and NaF - PET show suspected mets in four spots in the spine ribs plus one spot in the iliac bone, with my doc estimating the risk at 50 %; the spots are such that he cannot be sure. He says we will only know in April, with a new PSMA when I have been on ADT for six months."

It is true that if your bone lesions disappear or reduce after 6 months of ADT, they are certainly metastases.

Do you know if there is reason to believe added systemic therapy would be beneficial in a case like mine, Gleason 9 with only confirmed mets in lymph nodes?

Here is the evidence that whole pelvic radiation plus adjuvant ADT can still be curative if there are only pelvic LN metastases.

prostatecancer.news/2016/08...

With GS 9 and IDC-P, I think you should consider as intense a radiation treatment as possible- brachy boost therapy and 2-3 years of adjuvant ADT (possibly with ADT intensification as well, if you can get it. However, if there are indeed multiple bone metastases, it would probably not be useful. You can decide in April when you know more.

In any case, I suppose a biopsy of a met in a lymph node is not easily done...

True - it depends on the size.

I have not done any germline testing, since there is no history at all of prostate cancer in my extended family.

It is easy and cheap in the US, and NCCN is advocating that all men with metastases should have it.

[Purple-Bike in reply to Tall_Allen]

Thanks again Tall Allen,

Do you think it would be a good idea to get systemic treatment already now, 4 months before I know whether suspected mets in bones are there or not?

I recall seeing posts from you about getting aggressive treatment early.

On ADT now, for my GS9, IDC-P, mets confirmed in lymph nodes.

[Tall_Allen in reply to Purple-Bike]

Do you really have to wait 6 months? If they are indeed bone metastases, the shrinkage should become apparent after about 2 months.

[SUPERHEAT12]

Had low psa but Gleason 9. Did 43 sessions of IMRT radiation as well as ADT. With Dr Myers did intermittent ADT. Worked well but after ten years, and the loss of my prescription drug coverage, I quit ADT and Avodart. Got metastasis in the bones. Dr. Myers put me back on Avodart and all the supplements. So far it seemed to work.

[Purple-Bike in reply to SUPERHEAT12]

You have it in the bones, must be heavy for you. I will find out in April if I have it there.But intermittent ADT worked for you for ten years - with no castration resistance? wow. Lupron, six months on, six months off?

And then you stopped, and the cancer roared back?

[Hidden]

I am sorry and I speak as someone who dealt with this crap in 2004. I don’t have time to properly explain, however, please look at my previous posts and think about Lupron plus systemic treatment above listen to your pro...... that is what you are paying him for..... he has more knowledge than you will ever get by reading....... good luck.

Gourd Dancer

[j-o-h-n]

If I go... will you also carry my bags?

Good Luck, Good Health and Good Humor.

j-o-h-n Monday 12/14/2020 6:55 PM EST

[j-o-h-n]

Those are too big to carry.... call a Skycap....

Good Luck, Good Health and Good Humor.

j-o-h-n Monday 12/14/2020 7:04 PM EST

[j-o-h-n]

I do love blondes (women) and with all my scans I do speak "SCANdinavian", and I love Danish pastry but it's too clean there..... I need NYC dirt to survive........

Good Luck, Good Health and Good Humor.

j-o-h-n Monday 12/14/2020 7:12 PM EST

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

Dirty Dogs Sabrett Truck!!!

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

Ahhhhhhhhhhhhh yes.......... and the proprietor pissing in a gatorade bottle when there aren't any customers on line..... NY NY it's a wondeful town 🎵

Good Luck, Good Health and Good Humor.

j-o-h-n Monday 12/14/2020 7:45 PM EST

[j-o-h-n]

Too many joints......

Good Luck, Good Health and Good Humor.

j-o-h-n Monday 12/14/2020 7:56 PM EST

[j-o-h-n]

I didn't want to be blunt...........

Good Luck, Good Health and Good Humor.

j-o-h-n Monday 12/14/2020 8:02 PM EST

[j-o-h-n]

We have a word for that in Greek, it's called incest.....

Good Luck, Good Health and Good Humor.

j-o-h-n Monday 12/14/2020 8:20 PM EST

[j-o-h-n]

have a blunt and chill....

Good Luck, Good Health and Good Humor.

j-o-h-n Monday 12/14/2020 8:28 PM EST

[j-o-h-n]

LOL Close enough..... Your bill will be in the mail shortly....

Good Luck, Good Health and Good Humor.

j-o-h-n Monday 12/14/2020 8:53 PM EST

[Purple-Bike]

Oops - my apologies. Belatedly I see I posed a similar question 3 years ago, with TA writing the following comments to the first study I linked to above. It seems ADT + ARPI + chemo could be the best treatment option.....

From TA "I think you are misinterpreting that observational, retrospective study. It was not a randomized clinical trial among men with low PSA subtypes where some men were given ADT and some were not. It only shows that the low PSA subtype has poorer outcomes and doesn't respond as well to normal ADT. It argues for the opposite of your conclusion - treatment intensification, rather than less ADT".