What is the role of androgen deprivat... - Prostate Cancer N...

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What is the role of androgen deprivation and prostate cancer treatment?

mperloe
mperloe

QUESTIONS:

Does ADT need to reduce both T and DHT to be effective?

Can you get the same benefit from using medication to block 5 alpha reductase the enzyme that converts T to DHT?

How long is ADT required?

Does ADT increase sensitivity to RT treatment?

As PSA levels are dependent on testosterone or DHT, with ADT are we simply lowering the production of PSA suggesting that things are going well, when we’ve merely suppressed the PSA while the PCa continues to grow?

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ADT is used in many different situations, sometimes as an adjuvant therapy, sometimes as a life-long therapy, sometimes after primary therapy failed. Also, ADT may also include combinations of different kinds of hormonal therapies, or monotherapy with bicalutamide. It may be intermittent or continuous. It may be by orchiectomy too.

What is the reason you are using it and what are you using? (it may help you to get responses if you fill out a profile)

To answer what I can without more specifics...

Does ADT need to reduce both T and DHT to be effective? DHT is a metabolic biproduct of T, so reducing T will reduce DHT

Can you get the same benefit from using medication to block 5 alpha reductase the enzyme that converts T to DHT? No, because T activated the androgen receptor.

How long is ADT required? It depends on your situation

Does ADT increase sensitivity to RT treatment? Yes.

As PSA levels are dependent on testosterone or DHT, with ADT are we simply lowering the production of PSA suggesting that things are going well, when we’ve merely suppressed the PSA while the PCa continues to grow? Growing PCa releases PSA into the serum. That's why PSA is used as a biomarker for PCa.

mperloe
mperloe in reply to Tall_Allen

I'm sorry I did not identify as a reproductive endocrinologist, not a urologist.

But, actually there is little or no correlation between serum T and DHT levels and serum levels. I'm really trying to understand this from a molecular biology level.

Actually, in the prostate, the primary effect is from DHT, not T.

I was hoping for a bit more specificity on published studies that might indicate how the benefit is brought about. When combination seeds and beam are combined, some studies show no additional benefit. How does ADT improve sensitivity. As RT kills the fasting growing cells, if we slow growth with ADT, are we not allowing some cells whose growth is slowed to survive the RT?

But, if you are on ADT which shrinks the gland whether or not you have cancer, how do the you the reduction is due to reducing the gland size or killing cancer?

What you have suggested is the common understanding, but it is not clearly supported by studies.

Tall_Allen
Tall_Allen in reply to mperloe

DHT is a stronger activator of the AR, but T is also an activator (as PCa progresses, other ligands become activators). You seem to believe that DHT (and estrogen) are not metabolic byproducts of T? It is definitely true that prostate levels of these steroids are much higher than serum levels.

I take it that you still have a prostate, and there is cancer in it - what grade? What is your risk level? ADT is not useful for favorable risk PC, only for unfavorable risk PC as an adjuvant treatment for primary radiation. It would really help if you would give your diagnosis. You may want to put it in your profile.

ADT weakens prostate cancer cells, making them more radiosensitive. This helps when the radiation provides only sublethal killing. ADT also kills hormone-sensitive prostate cancer directly - activation of the AR is necessary for mitosis, and cells that cannot undergo mitosis cannot survive.

PSA as a biomarker after radiotherapy takes time. It is not immediate, as with RP. With adjuvant ADT, PSA will become undetectable within about 2 months and stay there until adjuvant ADT is over and T returns to normal levels. It is only then that PSA becomes a useful biomarker for PCa. Healthy prostate cells do not release significant amounts of PSA into the serum, only damaged prostate cells (from PCa, BPH, and prostatitis) do. So nadir PSA below 0.5 ng/ml after T has been restored is prognostic for a lasting cure.

mperloe
mperloe in reply to Tall_Allen

Thanks for your response. I'm aware that DHT and E2 are metabolites. Interesting I've not read about E2 role in prostate. I have read that 5 alpha reductase blockers will lower tissue DHT, but as a result T rises.

I am 69 yo and have a 3 month Tulsa Pro prostate. My PSA was 4, with Pirads 4 lesion 1 cm on the left side on 3T mp MRI. The biopsy read one GL 4+3 core (GG3) with cribriform pattern. Prolaris shows a intermediate to high risk for death from prostate cancer over 15 years. I had planned Tulsa Pro in Finland with a PET scan but Covid forced me to look closer to home. When a treatment slot opened in Sarasota with Dr. Scionti, I postponed going to UCLA to participate in a GA68 PSMA scan until next month. I had the entire gland ablated, and my post treatment PSA came back at .4ng/ml today!

My question has to do with if the PET scan detects nodes or distal oligometastasis, it seems most radiation oncologists recommend 1-2 months of ADT pretreatment. My guess is that Lupron or Zoladex would be the first go. As I was on testosterone replacement prior to the PCa diagnosis, I wonder if there would be some point that resumption of T replacement might be considered along with one of the modern 5AR blockers.

A few post earlier this article was attached. It is a good starting point for those wanting to understand the research that goes into treatment planning.

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

Tall_Allen
Tall_Allen in reply to mperloe

Thanks, that helps a lot. So you've had local treatment, and you have not had ADT. If the PET scan is positive for pelvic lymph nodes and/or distant metastases, you're wondering whether adjuvant ADT will be required for oligometastatic SBRT treatment? The answer is no. They give a very high dose of SBRT that does not require radiosensitization. In fact, in the ORIOLE trial, men who've had ADT within the last 6 months were excluded.

If you are wondering how to interpret your PSA of 0.4 ng/ml 3 months after whole gland TULSA-PRO treatment, the answer is no one knows. Unlike RT, there is no long-term data on PSA after this treatment. You are the guinea pig, and we will all learn from your experience.

As to the resumption of TRT after whole gland ablation, that is another big unknown. Within the necrotic tissue are tiny pockets of extant cells; maybe benign, maybe cancerous. So it is unknowable whether TRT will fuel growth. At any rate, you will want to see a low, stable PSA before TRT because testosterone will probably influence PSA. You want to be very sure that all the cancer is gone before TRT. I recommend an mpMRI-targeted biopsy within a couple of years. Importantly, you will have to find a radiologist who knows how to read an mpMRI on ablated tissue, and a pathologist who knows how to interpret histology on ablated tissue.

mperloe
mperloe in reply to Tall_Allen

Thanks. That all makes sense. When I opted for Tulsa Pro I saw it as looking at a tumor that was potentially aggressive that would lead to AS. I've been advised to do we month PSA and mpMRI at one year. I would not plan on considering TRT until that is reviewed. My non ADT T runs on the 20-30 ng/ml, so autologous mini ADT without the expense of leuprolide.

The introduction of Tulsa Pro and using the PET scan prior to initial treatment will certainly create more questions than answers at first. Advanced and the addition of rapid SBRT treatment will redesign how we approach this condition. Equally important is to build awareness and encouraging to speak out and share their stories.

Tall_Allen
Tall_Allen in reply to mperloe

My problem with treatments like TULSA-PRO and oligometastatic treatment are that they are oversold. I'm not against either treatment, but patients should understand the risks of using these treatments before there is actual convincing data. For focal ablation, here are some unresolved issues. Some may be solved by whole gland ablation, but of course, the morbidity risk is higher:

prostatecancer.news/2016/12...

mperloe
mperloe in reply to Tall_Allen

Actually speaking to those who have been doing Tulsa Pro, there does not appear to be increased complications with hold gland vs focal. As PCa is often multifocal, I believe that focal treatment is riskier. While TPs 510k is for shrinking the gland it is impossible carryout studies that can provide long term data sufficient for a cancel treatment. Many of the newer RT protocols do not have long term results. The ability to repeat or consider RT or RP if there is a recurrence, is a benefit. Treatment after RT with recurrence offers somewhat limited more complicated options. I wish there was more funding to complete the necessary studies.

Tall_Allen
Tall_Allen in reply to mperloe

I think focal is riskier too. But then what is the benefit over, say, SBRT, IMRT, hypofractionated IMRT, or BT, all of which have 10 years of follow-up data? It's not just a funding issue, it just takes years of f/u. SBRT began in 2003. RARP began in 2000.Arguably, one can look at those as incremental improvements over their predecessors, IMRT and open RP, respectively. Thermal ablation is a completely different approach.

I would never use salvage RP after radiation or ablation. The tissue becomes sticky and difficult to remove. There are many good salvage therapies after RT.

mperloe
mperloe in reply to Tall_Allen

I've used MRGfUS to treat uterine fibroids. It does not effect surgery. Tulsa Pro is different in that you have direct temperature feedback with 1.5 mm accuracy. HIFU , FLA do not offer this same degree of control. We used focal US for fibroids. FDA was going to require 10+ years of data. The company didn't have the funds.

Tall_Allen
Tall_Allen in reply to mperloe

All I've seen are reports like this after HIFU:

"As a reported complication of HIFU therapy is formation of rectal adhesions and fistula formation, during the surgery, posterior dissection of the vas deferens and seminal vesicles was performed first to ensure the prostate was not adherent to the rectal wall prior to any irreversible steps (urethral cut) being taken. A posterior prostatorectal plane was developed bluntly toward the apex of the prostate. Endopelvic fascia was not incised as part of the SMART technique (Samadi Modified Advanced Robotic Technique) in order to decrease risk of injury to neurovascular bundles on the lateral portion of the prostate and preserve erectile function in the patient. Bilateral neurovascular bundles were then spread without any difficulties."

hindawi.com/journals/criu/2...

What clinical reports have you seen of salvage surgery after Tulsa Pro to the prostate? It's one thing to have a theoretical expectation, and quite another to have success in a clinical trial. Hopefully, this is a decision you will never have to make.

mperloe
mperloe in reply to Tall_Allen

HIFU is to Tulsa PRO as TP is to HDR brachy. They are each different and the unique profile with Tulsa will need to be determined. A negative PET scan will be quite reassuring.

TA what about my type of cancer, “ductal adenocarcinoma” what should be my “thing to watch for” because my PSA was never over 3.6

You will have to monitor progression with CT scans mostly. Perhaps occassional FDG PET scans.

Ty

I understand your query as it puzzles me as well.

It is a compromise decision. On one hand some ADT before PSMA PET/CT increases PSMA and hence increases the test's detection rate. On the other hand, there is a school of thought believing that the later initiation of ADT- the better, i.e ADT time span is crossly bounded. That is, it doesn't function additively, but timely. So, a short duration of initial ADT followed by a long pause one can trigger the ADT "timer". For this reason I am trying to find the lightest combination of ADT kind and duration that will enhance PSMA with the least possible chances of triggering the ADT "timer". Info pertinent to this is very scarce and will probably take a best guess decision in the end. Let us know what your own mix will be.

Hey mperloe! Adt does not just suppress our PSAs it suppresses pc also . We have many adt choices today . I’ve been on constant adt for 5 years . 4 years clear of all visable signs and PSA undetectable. Without adt I surely would have died years ago. It’s a trade off life for side effects . A personal choice . I also have done much alt medicine. I’m directed in diet and nutrition by a naturalpathic oncologist. Live well and take good care of your life. Adt or no adt . Good luck putting the pc down . Scott 🌵

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