To ARi or not to ARi, that is the que... - Advanced Prostate...

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To ARi or not to ARi, that is the question

FinnO profile image
15 Replies

I had a 12/22 .71 PSA, 6mo doubling time and PSMA confirmed 5mm met in right pelvic lymph node (after prior failure of RP and fossa IMRT to “cure”). I have been on Orgovyx for a month and start 28 sessions of IMRT to the pelvic lymph nodes with boost to known met next week. Tolerating Orgovyx very well and so far happy I pushed for it vs Lupron. My treating RO wants to stop ADT after 6mos and go into AS mode. My highly regarded oncologists three (2 ROs, 1MO)  all recommend against adding an ARi ( they say no studies to support ARi in my particular case and/or risk/reward ratio too high for me). My urologist however is pragmatic and after a solid discussion of pluses and minuses including risk of tNEPC he supports my choice because “it’s you not me that has to live with the outcome”. So even though now I have a Nubeqa Rx at my disposal I don't take any drug lightly. And I just received my prostate tissue Decipher score of .36 (.45 is the high cutoff for low risk). So given all this if there is any similar experience out there:

- Does adding an ARi (Nubeqa) on the treatment plan have merit or is it now a waste of a good future weapon? 

- Is the plan to stop ADT after 6mos a good one or is the 2yr ADT SoC still preferable? Getting my "woody" back sooner rather than later would be a plus.

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FinnO
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tango65 profile image
tango65

Having a nodal relapse without distant mets, I will go with the Stampede trial and do 2 years of ADT and abiraterone plus the radiation.

thelancet.com/article/S0140...

FinnO profile image
FinnO in reply totango65

Tango thanks for the reply. I presented STAMPEDE as well as ARCHES as at least partial justifications for adding abiraterone (or other ARi) to my treatment plan. Unanimous conclusion was that they weren’t specific enough studies to my case to warrant usage given potential side effects. I am on board with the radiation but given post-Covid reality of a medical community that advocates en-masse taking drugs with ZERO clinical trials I’m not inclined to blindly follow this advice.  Having said that, I have cardiac disease in the family (although I lead a much more heart-friendly life than my ancestors) and tried to research the various ARi options as best I could. Darolutamide appears to be more effective with a better SE profile than abiraterone or others.  Do you know of any data out there suggesting I am wrong about this conclusion to choose darolutamide over one of the others? I have time to change course.

tango65 profile image
tango65 in reply toFinnO

I understand you had previous radiotherapy to PF and that your situatio may be different.

However, having lymph nodes affected it is a high risk situation and it should be treated as such.

I would request 24 months of ADT plus Abiraterone or darolutamide (there are not data with darolutamide) with the whole pelvis radiation going as high as possible.

At least consider to discuss 24 months of ADT. The Radicals HD just published some results indicating that 24 months of ADT offer an advantage over 6 months of ADT.

ascopost.com/issues/october....

Many things to discuss with your doctors. Classic situation to get a second opinion in a center of excellence.

Nobody in this forum have clinical experience in treating PC we just give some info and beliefs but the doctors have to decide.

FinnO profile image
FinnO in reply totango65

Thanks I had not discovered that link yet. Here is one I found regarding a current study of short term HT + radiation:

urologytimes.com/view/dr-ta...

I agree with your assessment (e.g. high risk). All my Onc opinions come from two CoE which is not lost on me for sure. Your "disclaimer" at the end is always good to note and rest assured that I am a data driven guy that is typically not satisfied with just one perspective. Aside from actual feedback from everyone on this forum of which most have spent more time in the trenches than I, the relevant study links that people like yourself and T_A provide are invaluable for researching and discussing the decisions we all need to make as our own treatment advocates. There is not much time to loose when it comes to that.

tango65 profile image
tango65 in reply toFinnO

The study you mention is for oligometastatic prostate cancer.

You have a recurrence with a node in the pelvis which may not be considered a metastasis if it is below the bifurcation of the iliac arteries.

Whole pelvis radiation, as far as the bifurcation of the aorta and 2 years of ADT plus an anti androgen may be very effective, even cure you if the node is in the territory of the internal iliac artery (N1 M0 cancer)..

FinnO profile image
FinnO in reply totango65

Thanks. T_A pointed out my lack of PSMA details in my profile which I updated. It is a 5 mm rounded met in the proximal right obturator lymph node.

tango65 profile image
tango65 in reply toFinnO

The obturador muscle is irrigated by a branch of the internal iliac. My understanding is that nodes in the territory of the internal iliac artery are considered N1.

N1 is when the cancer has spread to nodes in the pelvis.

tango65 profile image
tango65 in reply toFinnO

This link shows the proximity of of the obturator muscle to the prostate.(FIG 1).

Tall_Allen profile image
Tall_Allen

There is a clinical trial now for this situation. It gives 2 years of ADT randomized with or without Erleada for patients with pelvic LN metastases.

clinicaltrials.gov/ct2/show...

2 years of ADT+abiraterone is SOC for men newly diagnosed with pelvic LN metastases (stage N1). This was proved by the STAMPEDE trial:

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

There is only this retrospective study that shows the value of long-term ADT with positive nodes in the salvage situation:

prostatecancer.news/2017/12...

Decipher shows the risk of metastases in the next 5 or 10 years. It is irrelevant to your situation because you already know you have metastases. That ship has sailed.

Also irrelevant is tNEPC because you are considering adjuvant ARSi while hormone sensitive, which is entirely different from ARSi given to men who are castration resistant.

Also irrelevant is worrying about saving Nubeqa for later. You are taking it for a limited amount of time (2 years) after which you will hopefully be cured.

Also, you cannot stop and restart ADT and still be cured. That selects for ADT-resistant phenotypes.

FinnO profile image
FinnO in reply toTall_Allen

Tall_Allen thanks for these links. Good to see that trial underway. It’s not an option for me to participate due to logistics and having to change ROs. For that aspect of my next level of treatment (IMRT) I believe I am in the hands of one of the best. I do agree on the primary Decipher value but it doesn't seem all or nothing to me (or my oncs) as a useful datapoint. I have seen analyses that suggest it also has value in next phase treatment planning (at least for me) if for none other than to help validate what I am about to go through. Peace of mind is important to therapy. An example link. 

cancer.gov/news-events/canc...

That retrospective study on length of ADT that you wrote is interesting and I plan to present and discuss with my RO and MO. Fortunately I have time to research and decide on that aspect in a few months. See the link I added above to tango regarding a 6mo ADT study. I don't want to completely ignore QoL and how ADT may affect that.

Tall_Allen profile image
Tall_Allen in reply toFinnO

You are right that Decipher predicts distant metastases. That would include all lymph node metastases at or above the common iliac level (stage M1a). You did not say where your pelvic LN metastasis is.

The EXTEND trial that you cited above, should not influence your decision. Dr Tang is making an error (I notified him of his error) that many patients make and even some doctors who should know better make. The problem is this: He is treating PSA (not the cancer), and then he is using an endpoint that is almost entirely PSA (PFS at 22 months f/u) to decide whether ADT should continue. It is circular reasoning. You may want to read this article:

prostatecancer.news/2020/07...

FinnO profile image
FinnO in reply toTall_Allen

T_A, good reading in that article. I have some questions for you (since you authored) and I apologize if the answers are already in the article. Still consider myself a newbie trying to comprehend all the nuances to this disease.

“Men who were oligometastatic benefited from early, intense hormone therapy”

- Does “intense hormone therapy” just mean adding an ARSi to ADT?

“So it is possible, when such phenotypes are present and they are mixed with "normal" prostate cancer, to provide treatments that kill off the "normal" prostate cancer cells, leaving the low-PSA subtypes behind. Such a situation has been identified in patients heavily treated with chemo and enzalutamide. It is called "treatment-emergent neuroendocrine prostate cancer" (see this link) and has been identified in 17% of heavily-treated patients.”

- Does this assume ADT is in the treatment plan as well? If so, add that to my next question.

- What defines “heavily-treated patients”, the combo of chemo + enzalutamide (+ ADT) or a subset?

“The TROG 03.04 RADAR trial examined the duration of hormone therapy in high-risk men treated with radiation.  They found that, after 10 years of follow-up, men treated with 18 months of ADT survived longer, and reached castration resistance later compared to men treated with 6 months of ADT.”

- I am curious how the term of 24mos of ADT as an SoC come to be? I see 18mos in TROG and then a jump to 24mos in STAMPEDE. How much "SWAG" or "Rounding up" is built into those end dates? 18 is reasonably close to 24.

In my situation where the current RO plan is to go off ADT after 6mos followed by measure/watch PSA for results, if I decide I want to stay on ADT longer and since I started with one detected LN met would another PSMA scan after 6+ mos be a better way to confirm treatment success of that met rather than stopping ADT early and watching the PSA?

Thanks!

Tall_Allen profile image
Tall_Allen in reply toFinnO

"Does “intense hormone therapy” just mean adding an ARSi to ADT?" Yes.

"- Does this assume ADT is in the treatment plan as well?" Yes, ADT is always the mainstay of all systemic therapies.

"What defines “heavily-treated patients”, the combo of chemo + enzalutamide (+ ADT) or a subset?" Chemo and ARSI -It can be sequential too. This has nothing to do with your situation.

"I am curious how the term of 24mos of ADT as an SoC come to be? " Based on the landmark DART 01/05 GICOR randomized clinical trial. Subsequent analysis found that 26 months is optimal with EBRT:

prostatecancer.news/2022/01...

However, this has nothing to do with your N1 situation. In fact, all patients with N1 were screened out of all those trials.

"would another PSMA scan after 6+ mos be a better way to confirm treatment success of that met rather than stopping ADT early and watching the PSA?"

No. hormone therapy kills stray cells that cannot show up on any scan or biopsy. You may like your RO and he may be a lovely person, but your RO is wrong, and has no evidence for doing such a potentially damaging strategy.

FinnO profile image
FinnO in reply toTall_Allen

T_A,

Thanks for the clarifications. "potentially damaging strategy" meaning proposing just 6mos of ADT?

Tall_Allen profile image
Tall_Allen in reply toFinnO

Yes. Stopping and restarting selects for resistant phenotypes.

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