Value of ADT in Post-Metastases Enviornment

[6357axbz]

If prostate has been successfully irradiated and all mets zapped so nothing is showing on a GA68 PET/CT scan, and PSA is undetectable, what is the benefit of continuing ADT?

[Tall_Allen]

Read this (it's as if it were written to address your question):

prostatecancer.news/2020/07...

[dac500 in reply to Tall_Allen]

I have always wondered how much PSA can radiation treated prostate produce. This article answers the question partly.

[6357axbz in reply to Tall_Allen]

I think I’m missing something. It seems we track success of ADT by its effect on detectable tumors, i.e., tumors long past the micro-metastatic state. This seems only natural because why would we initiate ADT if there are no detectable tumors present? Is ADT as effective on suppressing the micro-metastatic environment as it is on suppressing detectable tumors? I suppose this can be inferred from your article but it’s not immediately apparent to me.

[IrishDude in reply to 6357axbz]

I think the answer would have to be a hopeful yes. ADT is often given, as in my case, alongside radiation treatments in the belief that the radiation/ADT combo is more effective than the radiation alone.

[6357axbz in reply to IrishDude]

I get that but in your case we’re still dealing with the detectable mets the radiation is treating. The ADT shrinks and weakens the mets which assists the radiation.

[Tall_Allen in reply to 6357axbz]

As the article explains, you could usually track the success of systemic therapies, like ADT, based on systemic effects - serum PSA and detectable metastases. But you have tampered with serum PSA and detectable metastases, so they are no longer valid markers of success.

ADT is even more effective in killing off smaller metastases than it is at killing off larger metastases. That is why long-term ADT is used after radiation therapy for high-risk PC. It is also why stronger ADT (like Zytiga, Xtandi, and Erleada) is continued and slows progression and lengthens survival even after detectable metastases have been shrunk and PSA is undetectable after mHSPC. It is also why Nubeqa, Erleada, Xtandi and Zytiga slow progression and lengthen survival in men who are castration-resistant but have no detectable metastases.

[6357axbz in reply to Tall_Allen]

Thanks

[6357axbz in reply to Tall_Allen]

TA, what do you think about the study GP24 refers to below?

bjui-journals.onlinelibrary...

[Tall_Allen in reply to 6357axbz]

If you read my article, the ORIOLE trial is addressed.

[Break60]

If you have aggressive pca, you still have micromets so lifelong ADT is necessary. That's why I switched to estradiol patches. See my profile.

[6357axbz in reply to Break60]

Wow, you’ve had a lot of mets zapped. From what I remember reading most lifelong ADT patients are living with detectable mets. Are you or have they all been zapped?

[Break60 in reply to 6357axbz]

As you can see in my profile, based on undetectable psa for a long time, I HAVE NO DETECTABLE METS AND AM STILL CASTRATE SENSITIVE.

[6357axbz in reply to Break60]

It appears you’ve had some ADT holidays, correct?

[GP24]

Phuoc Tran at Johns Hopkins, who did the ORIOLE trial, suggests metastasis directed therapy to delay the use of ADT. Here is a citation from the introduction of a recent report:

redjournal.org/article/S036...

Introduction

The oligometastatic hypothesis postulates metastasis represents a continuum spanning a single lesion to widely metastatic disease. Along this continuum, and in between these two states, lies what is considered oligometastatic disease whereby individuals have a limited number of metastatic deposits [1]. The implication of the oligometastatic hypothesis is that those occupying this disease state might benefit from prolonged periods of recurrence free survival or even be cured with local therapies to the primary tumor and oligometastatic sites in conjunction with systemic agents [2].

Several studies have demonstrated improvements in progression free survival (PFS) and overall survival (OS) through aggressive treatment of oligometastatic disease, thus establishing a body of literature to provide support the use of metastasis directed therapy (MDT) [3-5]. Within the oligometastatic prostate cancer literature the STOMP and ORIOLE trials reported prolonged androgen deprivation therapy free survival and PFS with following MDT as compared to observation [6,7]. These findings are also supported by several retrospective studies showing sustained periods of PFS, ADT free survival, and time to next intervention with MDT [8-15]. Collectively these results have led to an increasing trend to treat oligometastatic lesions with MDT to improve OS and PFS, delay initiation of systemic therapies with unfavorable toxicity profiles, and offer treatment breaks for individuals amassing toxicity from systemic therapy.

With growing evidence to support the use of MDT in oligometastatic disease its use will continue to expand.

I just want to live the remaining years of my life with good quality and therefore do not want to have ADT for the rest of my life. To avoid the side effects of ADT I rather zap my mets as soon as they become visible with a PSMA PET/CT and thus delay ADT. Currently there is no proof that this will shorten my life.

Here is a slide illustrating the open question whether metastasis directed therapy makes sense:

up.picr.de/39359344mb.png

[6357axbz in reply to GP24]

Thanks for the informative post!

I have no problem continuing ADT after MDT. My QOL is relatively unaffected by ADT.

[GP24 in reply to 6357axbz]

I think one can assume that MDT plus ADT is a more aggressive therapy against the tumor. But you can probably make looong breaks then if you do intermittent ADT.

[6357axbz in reply to GP24]

Why do you think that GP?

[GP24 in reply to 6357axbz]

Why do I expect long breaks? If you make a break, it takes quite a long time for the testosterone to recover. After that period it depends how much tumor there is to increase the PSA value and make it reach the threshold you have agreed on with your doctor. When there is just very little tumor present because of MDT, it takes longer to reach this threshold. That is what I think.

[6357axbz in reply to GP24]

Do you believe that IADT is comparable with CADT as far as OS goes?

[GP24 in reply to 6357axbz]

It is the result of this study:

In this study of only metastatic patients, no statistical difference in either overall survival or progression‐free survival was shown between intermittent and continuous ADT and suggests that intermittent might be as safe as continuous castration.

bjui-journals.onlinelibrary...