Intensifying ADT?

[Purple-Bike]

I am fortunate to have found this forum with invaluable advice generously given, sometimes with opposing points of view which add to insights.

Any views about a preferred addition to ADT in a relatively newly diagnosed metastatic PC r would be most welcome, not the least since although doc and clinic are considered the best in my part of the world, I just get 60 minutes about every six months to communicate directly with him with nothing in between and I am soon to get that moment.

Given the aggressive type of my cancer, I understand that ADT intermittency or vacation is not an option. On the contrary, besides two years or so of ADT, intensification may be called for.

I have GS 4+5, low PSA 1.7 at dx last September, T3b/N1/M?, with four suspect mets to bones which will probably be confirmed as metastatic when I shortly get a new PSMA-PET. I had EBRT + brachyboost late last year. Monthly Firmagon injection, + 75 mg Bicalutamide (a compromise after input from the Forum and to not fully diverge from doc) . T 9ng/dl = 0.3 nmol/l, PSA below 0.1. Intraductal cancer in two of 16 samples (however in two of the "nicest" samples only 3+3 and 4+3, I have not been able to figure out if this makes it relatively benign).

Reading up on a multitude of posts of the Forum, and looking at the Prostate Cancer news from 2017 about best options for newly diagnosed metastatic men, my impression as a relative newbie here is that amongst the best options are abiraterone/Zytiga or Docetaxel (however, I recall somewhere seeing the latter not being good with presence of intraductal). Perhaps Erleada. Xtandi seems to be a killer for fatigue.

High-dose transdermal estrogen is intriguing given the lower side effects, but I guess it has too low efficacy for my aggressive cancer.

Side-effects so far of ADT are tolerable, perhaps aided by a rigorous diet and exercise, with a rise in CRP from 0.16 to 2.9 as the main concern.

As per advice from Nalakrats, I will try to get the clinic to arrange a biopsy of a met to see if it is from the intraductal or adinocarcenoma part of the pathology. I will shortly get the results of my germline testing from Color.

[Tall_Allen]

You are right that "Intraductal Carcinoma of the Prostate " (IDC-P) is not particularly a poor prognosticator when it is found with low grade Gleason scores. At any rate, the same therapies are called for. IDC-P is not something that shows up in metastases, it only shows up in prostate biopsies. Perhaps Nalakrats is confusing it with "ductal," which is more aggressive."Intraductal" and "ductal" are two different things.

Getting a biopsy of a met that is very small can be problematic, anyway.

What country are you in? Different therapies are available in different countries.

[Purple-Bike in reply to Tall_Allen]

Thanks, TA.

I live in Stockholm,Sweden, where all clinics have to follow the national guidelines for prostate cancer treatment, which are a few years behind the best available elsewhere which in my vicinity means a private cancer clinic in Helsinki, Finland which I have chosen for treatment. There may be some interesting research carried out at Karolinska Institute in Stockholm, but I have no contacts with that and I was denied access to it s one and only PSMA-PET machine which may well be the only one in this country, so far.

[donits in reply to Purple-Bike]

Hi, can you tell us what treatment you have been offered in this clinic, please? There the prices are very high, but life is more important than money.One of the good doctors is Dr. Timo Joensuu. More than 15 years ago he worked at HUS and there he treated a young (about 40 years old) patient with very advanced cancer (PSA was over 3500). This patient is alive and well known in Finland.

[Purple-Bike in reply to donits]

Yes, that´s the place. EBRT, brachyboost therapy, PSMA-PET, Firmagon, Bicalutamide. Will consider radiation to mets in the bones if these are confirmed, although benefits are not clear.

[Purple-Bike in reply to donits]

Also NAF-PET. Yes, it´s a fine doctor and clinic.

[Tall_Allen in reply to Purple-Bike]

Thanks for explaining that. I've noticed that Finland seems to have many good institutions for a country of its size.

Let me ask you a few questions that I'm not clear about:

(1) What is your current PSA? The reason I ask is that PSMA PETs do not detect prostate cancer much at very low PSA. If your PSA is now undetectable because of your ADT, there is little chance that even the most sensitive of the PSMA PET scans will be able to detect it. There is an experimental PET scan called (F18) PSMA-1007 that may detect prostate cancer when PSA is as low as 0.2 ng/ml. They are working on it in Germany.

There's a chart at the end of this article that shows the sensitivity of the various PET scans:

prostatecancer.news/2016/12...

(2) If the 4 bone metastases are large enough and are in a convenient place, perhaps they can be biopsied and examined with an IHC stains to see exactly what they are. If they do not express androgen receptors, it would be useless to try second-line hormonal agents (e.g., abiraterone, enzalutamide, or apalutamide). In that case, a combination of docetaxel and carboplatin may be much more effective.

It also may be useful to ask whether the bone metastases appear to be osteosclerotic (bone overgrowth) or osteolytic (bone erosion). They can tell that from an MRI or CT scan.

(3) Do the bone metastases (if that's what they are) cause you any pain?

(4) I assume that when you had brachy boost therapy, your pelvic lymph nodes were covered by external beam radiation. Do you know if (A) the coverage area included the common iliac lymph nodes (the coverage area was expanded recently), and (B) if a boost dose was given to the known enlarged pelvic lymph nodes.

[Boywonder56 in reply to Tall_Allen]

Thanks for that explanation on receptors t/a...

[Purple-Bike in reply to Tall_Allen]

Finland in general is slightly ahead in PC treatment so it's perhaps no coincidence that the brightest docs there have set up this clinic which is no 1 in Scandinavia and possibly a larger region as well.

1 PSA less than 0.1. Seems to be a mystery how mets will be confirmed or not but it has been promised. They know I have under 0.1

2. Most interesting. If mets cannot be biopsied, would the risk of non-expression of androgen receptors indicate docetaxel and carboplatin as the best option? Do you know how common non-expression is?

Could you say something about the importance of bone overgrowth vs erosion? Does it have implications for treatment?

3 No pain whatsoever. The suspected mets are tiny.

4 Don't know. I suppose the answer will say something about the efficacy of the radiation. Before meeting doc, I will make a list of written questions including this one and get the response verbally.

[Tall_Allen in reply to Purple-Bike]

1. They cannot promise that it will detect cancer if your PSA is only 0.2. A negative result does not mean that it is not prostate cancer, it only means that it is under the limit of detectability by that PET scan/CT.

2. It is more common in low PSA types, as are osteolytic metastases.

3. If there is pain, you may qualify for Xofigo.

[Purple-Bike in reply to Tall_Allen]

Besides PSMA-PET, I will get tested with NaF-PET. Perhaps that is the answer?

[Tall_Allen in reply to Purple-Bike]

NaF is even lower sensitivity and depends on active growth.

[Hidden in reply to Tall_Allen]

I'm curious why you say intraductal is not a poor prognosticator or what exactly IDC is prognostic of. I listened to Dr. Epstein at the very last question of his talk - youtube.com/watch?v=9qsrtQi...(Not working as expected?) -and he said "IDC is one of the worst prognostic factors in cancer even in the study of advanced metastatic cancer, even then its ends up being prognostic. Having said that, again most of the time we see it with high grade cancer, probably is not critical." and then goes on to describe the crucial difference between PIN and IDC. I'm not sure what he is saying.

[Tall_Allen in reply to Hidden]

That is a simplistic view, suitable for a presentation. A deeper dive reveals that IDC-P is not a single entity. Both the type of IDC-P and its prevalence dictate its prognostic significance. When there is very little of it, it is low grade, and it is associated with GS6, it adds little to the prognosis, especially when the patient is already known to be metastatic:

urotoday.com/conference-hig...

auajournals.org/doi/10.1016...

ncbi.nlm.nih.gov/pmc/articl...

pubmed.ncbi.nlm.nih.gov/260...

[EdBar]

I was dx with G9 metastatic PCa, I took the kitchen sink approach as prescribed by Snuffy Myers, you can read my profile to see what I’ve done. So far so good, I’ll be reaching my 7 year dx anniversary tomorrow, God willing. My PSA has been undetectable for 6 of those years using an ultra sensitive test, however lately it’s been “flickering” detectable. We’ll see where it goes but given my original dx and prognosis the Snuffy Myers approach has served me well.

Ed

[Purple-Bike in reply to EdBar]

Read your profile and posts. A most encouraging story. Will research some of the items you are taking.

[noahware in reply to Purple-Bike]

You might also research the Dr. Bob Liebowitz (Compassionate Oncology) approach... he likewise used Lupron and Casodex and Proscar (triple blockade) but did it along with chemo, as well as anti-angiogenic meds.

His approach was to do this for 13 months, but then stop ADT as he believed it was a possible way to delay becoming castrate resistant. For some men he then administered T in a modified version of BAT. I am not suggesting this outside-the-box approach, but it is interesting to watch his lectures. The main point being, it was an "intensification" approach that theorized an early deployment of ALL weapons could be better than a sequential approach.

[Purple-Bike in reply to noahware]

Thank you, most interesting, will research.

[john205]

Your circumstances are somewhat complex and I cannot advise about what to do next. However, my experience with docetaxel, added to Lupron, was tolerable. I have high burden bone metastatic prostate cancer, Gleason 8. I had good response for 2 1/2 years with that regimen with suppression of metastatic sites and regression of primary cancer, so that was good. In my case, the docetaxel was tolerable, other than some mild nausea and some fatigue in the middle week of each cycle, and low WBC at the same time. I completed that 2 years ago.

You also had some condern about Xtandi. In November 2020 my PSA began to rise, although the imaging was still good, and my oncologist recommended adding Xtandi, based on current standard of care supported by research. I began that in November and my PSA dropped to the lowest ever by December . The fatigue has not been too bad. It's hard to distinguish it from normal fatigue for a 70 year old, or related to sleep variation. Maintaining physical activity has helped, mostly walking 5-10 Km almost every day. Also avoiding weight gain - the ADT makes me hungry so I have to be careful with that. I hope that helps.

[Purple-Bike in reply to john205]

Thank you for the insights. Docetaxel may be a strong candidate.

[Boywonder56]

My dx simmiliar gl 8/9 ductal histology in all pos samples. 6......i would suggest erleada as im poster boy for titan trial...has been working 4 + yrs since started adt in 1/17....expensive to those wo ins. But i believe a game changer as far as extending bad prognossis...im sure u have been told...its an aggresive form.... I could not tolerate the casodex and I had to wash it out to be on the trial anyways that's just my two cents