Triplet therapy question

[Papa1]

I had 8 weeks of radiation and two years trelstar in 2016. PSA undetectable thru spring 2021. Rising PSA. Bone scan and AXUMIN found three bone Mets in sternum. Treated with spot radiation. PSA still on the rise after treatment. PSMA scan found numerous other small bone mets in spine and ribs. Started Lupron, Abiraterone and prednisone Nov. 1, 2021. Due for second 6- month Lupron shot on Monday.

Was I ever a candidate for triplet therapy? The term “newly diagnosed” has me confused.

If yes, have I missed the boat? I have appointment with MO on Monday.

Treating now with Arif Hussain at U of Md. I have ready access to Sam Denmeade at Hopkins if I decide to switch.

Advice welcome.

[tango65]

Newly diagnosed means that when the cancer was diagnosed metastases were already present. The triple therapy is the first therapy in that situation. My understanding is that the data on triple therapy does not apply to pretreated cancers.

[Papa1 in reply to tango65]

Thanks.

[tango65 in reply to Papa1]

I wish you the best of luck.!!

[Papa1 in reply to tango65]

Thanks. I’m doing well. Light side effects. Waiting for labs on Monday, No reason to think they won’t be good. Life is generally good.

[Tall_Allen]

No, you were never a candidate for triplet therapy. It is only for patients who were metastatic when they were first diagnosed.

[Papa1 in reply to Tall_Allen]

Thanks.

[Schwah in reply to Tall_Allen]

But wouldn’t it be logical that it would also be helpful to men with BCR when they are first diagnosed with metastasis ? I mean why no would it work for one and not the other?

Schwah

[Bethpage in reply to Schwah]

I would like to understand this as well.

[MateoBeach in reply to Schwah]

Agree. The next logical circumstance to test Triplet therapy would be at BCR with +mets but before any prior systemic therapy.

[Schwah in reply to MateoBeach]

My MO is very proactive. He did the triplet when I had BCR with mets and that was before the study. He was also using Zytega snd Lupron long before the latitude study proved its efficacy.

Schwah.

[Tall_Allen in reply to Schwah]

This is the kind of "logical" thinking we have to protect against. Medical science is based on empirical observation, not "logic" (no matter how convinced you are of your "logic"). The biology of BCR is very different from the biology of de novo metastases. We know they are very different states. Recurrent men with "metachronous" metastases have a very long expected survival. De novo with "synchronous" metastases have a much shorter expected survival. Biologically, they are very different diseases ("phenotypes"). There is a movement among researchers to make such distinctions based on individual cancer biology.

Deek et al. conducted a retrospective analysis. They categorized metastatic men into groups according to metastatic burden as follows:

(1) Biochemically recurrent, but metastases too small to detect/micrometastatic (n=45)

(2) Oligometastatic (1-5) at time of recurrence (n=102)

(3) Polymetastatic (6+) at time of recurrence (n=22)

(4) Newly diagnosed (de novo) as metastatic (n=125)

These groups are ranked in increasing aggressiveness with radiographic progression increasing, time to castration resistance decreasing, and overall survival decreasing going down the list. Number of metastases detected were also associated with increased progression, less time to castration resistance, and lower overall survival.

They biopsied prostate cancer from 294 patients, mostly (91%) from prostate tissue and (9%) from metastases. They genomically characterized the tissue according to whether there were the following mutations:

• tp53

• WNT pathway genes

• cell cycle genes

• DNA double strand break repair genes

• PI3K/AKT/mTOR pathway genes

They found that the incidence of tp53, and DNA-double strand break gene mutations were associated with number of lesions. TP53 had the strongest association with radiographic progression, shorter time to castration resistance, and shorter survival. WNT gene mutations also seemed to differentiate between oligo and polymetastatic recurrence.

This suggests that the biology of recurrent PCa is very different from the biology of of de novo PCa and requires different therapies.

europeanurology.com/article...

[NickJoy in reply to Tall_Allen]

Thank you for this - it explains a lot.

[Papa1 in reply to Tall_Allen]

Allen- thanks for this enlightening exposition. You have not only answered the “what” but also the “why.” My initial question was the result of a bit of lawyer overthink; did “newly diagnosed” apply to mets or pc with mets? Most helpful. You are a treasure to this group.

[j-o-h-n]

Like winning the Trifecta...........

Good Luck, Good Health and Good Humor.

j-o-h-n Wednesday 04/27/2022 7:17 PM DST