Should/Can I take zytiga/xtandi et al without metastasis diagnosis

[Velohomme]

Background...

Diagnosed in 2016: Gleason 9, PSA 10.5

Prostatectemy 2016: positive margins, no other evidence of spread. Post-op PSA = .11

Adjuvant radiation (prostate fossa only, with Lupron) 2017: Post radiation PSA = undetectable.

Recurrence 2018 (PSA .2): 3 week doubling time. PSMA and choline scans...could not find anything. When PSA got to 4.5 started Lupron.

Lupron round 1: 2018-2019, undetectable PSA.

Lupron vacation in 2020: PSMA scan, ultrasound. Nothing found.

Lupron resumed when PSA at 2.5.

PSA test today (5 months after resuming Lupron): .245

(the rate of decline in PSA is definitely flattening out and looks like it won't get lower than .2 this time).

Questions:

It seems very likely that my PCa is micro-metastatic but without proof on scans I am technically non-metastatic.

Both of my doctors (Kwon from Mayo and Fong from UCSF) have discouraged adding zytida or xtandi (though I am going to ask again now).

Given that I am castrate-sensitive and "non-metastatic" can I get zytiga/xtandi or do I need to find a trial?

Is there data that supports taking zytiga or xtandi now vs. waiting for castrate resistance?

Thanks for any help you can offer.

[Hidden]

As far as I know, there is no evidence to support the use of ADT plus an additional anti-androgen for non-metastatic, hormone sensitive PCa.

You are likely to get quite a while out of ADT alone so just ride that out and then add something when you become castrate resistant. That could be a long time from now.

[Velohomme in reply to Hidden]

Thanks Gregg

[Longterm101 in reply to Velohomme]

Hope your staying well

Keep livin!!

[Tall_Allen]

Here's some evidence from trials:

urotoday.com/conference-hig...

meetinglibrary.asco.org/rec...

It's not yet standard of care, so you would need a trial to get the drugs. I know someone who did the following trial and is so far at undetectable PSA with no current hormonal treatment:

clinicaltrials.gov/ct2/show...

[Velohomme in reply to Tall_Allen]

Thanks TA. Perfect studies for my question. Clearly there is an advantage for PSA progression.

[Chris52981 in reply to Tall_Allen]

Is it more helpful if you are metastic but hormone sensitive to Add a second - like is their studies that show it keeps people hormone sensitive longer

[Tall_Allen in reply to Chris52981]

Yes. Zytiga, Xtandi and Erleada, when added to ADT, all keep metastatic men hormone sensitive longer. So does docetaxel.

[Jpl506]

My Dx is very similar to yours, G9, PSA 9. No detectable spread via standard imaging. I had SBRT in June but I have been on Lupron + Erleada since March. My MO and RO (Liu and Kishan at UCLA) both said said their studies show better long term control for high Gleason grades using advanced ADT. I’m expected to be on the combo for 18-24 months. I’m not on any trial.

[Velohomme in reply to Jpl506]

Thanks Jpl506. Did your insurance cover the Erleada?

[Jpl506 in reply to Velohomme]

Yes, and the drug company covered my co-pay so it’s $0 out of my pocket.

[GeorgeGlass in reply to Jpl506]

how has the erleada made you feel. Different than just Lupron alone?

[Magnus1964]

You do not have to be metastatic to receive xtandi or zytiga. If cost is your concern I can give you a reliable connection in India.

[Velohomme in reply to Magnus1964]

Thanks Magnus.

[Schwah]

If your doctor won’t approve it, you may want to try the prostate oncology Specialist in Marina Del Rey California. All three doctors there think out-of-the-box and are pretty aggressive. They were doing Zytega with Adt long before it was proven in clinical trials . Lots of the guys go there. It would be interesting to see what they thought of it for you. They do phone appointments if it’s too far to travel.

Schwah

[Velohomme in reply to Schwah]

Thanks Schwah. I visited that clinic (Mark Scholz) last year. Scholz didn't suggest an ADT add-on at that time. I might poke him again.

[StayingOptimistic in reply to Velohomme]

Please let us know what dr. Scholz Suggests at this time. Thanks

[Schwah]

Yes bring him up to speed and see what he suggests. I trust his judgement greatly.

Schwah

[Velohomme]

Great information guys. Thank you so much.

The studies that Tall Allen cited show clear evidence of improvement in PSA progression. I'm wondering about the bigger picture: survival.

If I take zytiga et al now I will likely get more time before resistance. But I think the implication is that zytiga would no longer be a weapon after I become resistant. Is the overall survival better?

Both Kwon and Fong preferred deferring zytiga until later. Fong "doesn't want to use all our bullets" and Kwon suggested it is harder control after resistance (which is probably the same point as Fong's).

Personally I would shoot all of my bullets at once if it gets me longer survival. I feel like "more bullets" makes the MO feel better but is not necessarily the patient's goal (definitely not mine).

Any thoughts?

[Longterm101 in reply to Velohomme]

I read the OS difference between ADT and zytiga or xandi is about 3-4 months

Not sure it’s that big of an advantage

[GeorgeGlass in reply to Velohomme]

Did you get a clear data picture of what the overall survival rates were comparing ADT first and then using a 2d line (xtandi, erleada, zytiga) following psa rise while on ADT alone VS. just using ADT with a 2nd line drug right from the start? I read all of those links that TA provided but it didnt seem to take into consideration the part about adding the 2nd line drug after the ADT alone started to get rising PSA. You know what I mean? What is the average time to OS/death?

[Velohomme in reply to GeorgeGlass]

Hi George. I understand your question. No, I cannot find any studies directly comparing survival with the 2 strategies:

1. Start (while hormone-sensitive) ADT+2ndline

2. Start (while hormone-sensitive) on ADT only until castrate resistance, then add 2ndline

[GeorgeGlass in reply to Velohomme]

The stampede trial and some of the statistics cited on this post show results that show short life spans. I would like to see more results focused on low volume cancer. Looking at people who live closer to 8 years show similar outcomes whether they use adt alone or as the other stuff early. There is a bigger lifespan difference for people who live less than 4 years. In other words the chemo benefits or other AR drugs benefit early on but then revert back to the norm after a certain amount of time. It may not end up exactly even but it may be like 45% vs 35% OS after 8 years, so taking the extra stuff is, in a way, hoping that you will be part of that 10% grouping that keeps you alive a year longer. I realize that some of the ardent advisers on here that suggest aggressive treatment early, might take umbrage to my loose observations. I do have a chart that supports my comments. I’ll have to send it later when I unearth it.

[Hidden in reply to GeorgeGlass]

Who are you using as a loose observation? And given that, besides the stampede and latitude trials, who among us have been on these meds for 4+ years?

[GeorgeGlass in reply to Hidden]

maybe my words were too loose. I was referring to a specific study result comparing the early usage of chemo. It had increased OS but the two lines on the graph got closer together around 8 years. I cant remember when the data says about erleada, zytiga and xtandi exactly. You probably know better than me right now because I have too many other things going on in life to be as accurate as I want to be. What are your thoughts: prostatecancer.news/2017/06...

[Hidden in reply to GeorgeGlass]

My thoughts are this: I think it is accepted that pca is an older man's disease. Starting with this assertion, the os is hard to determine because it includes deaths from all causes.

It's the css that I'm more interested in and those numbers are still not very good because the newer 2nd line adt have extended css a good bit and I believe the css is still increasing albeit at a slower rate.

For me personally, and probably a good example for the OP, I'm HS NM and currently taking Eligard with Zytiga. My psa is currently < 0.01.

You can read my bio for more details on my treatments to date.

[Velohomme in reply to Hidden]

css = ?? time to metastisis? to psa progression?

[Hidden in reply to Velohomme]

Cancer Specific Survival

[GeorgeGlass in reply to Hidden]

Makes sense. What do the studies show for css advantage of adding 2d line to adt vs adt alone. Have they updated that recently based on extended data ?

[Hidden in reply to GeorgeGlass]

That I have not been able to answer...maybe TA would know. He does a great job translating studies so the average person can understand.

But being only 55, I'm more likely to die of PCA than anything else so that is why I'm interested in CSS and not OS.

A longer PFS should translate into a longer CSS.

[GeorgeGlass in reply to Hidden]

I agree. I’m in the same boat as you. If seen the days from stampede but I’d like to see the current days of the study is still ongoing. I’ve also never seen clear evidence that adt alone category men got on a2d line drug immediately after their adt started failing to spies the psa. If they didn’t do that, then the study comparison would be worthless.

[Hidden in reply to GeorgeGlass]

On a different topic.....lately I've been feeling great.....back in January (January 20th to be exact) I switch from 10mg to 5mg of daily prednisone. For several weeks I was very fatigued but I muddled through. But today I feel I'm back to normal again...I had a great workout and feeling zero fatigue.

Do you ever experience periods like this....I'm hoping it last for awhile.

[Hidden in reply to GeorgeGlass]

Check this out...I think is generally supports my preference for cssascopubs.org/doi/abs/10.120...

[magcali]

My husband's journey is somewhat similar to yours. After adjuvant radiation his PSA was undetectable for nearly two years, then a recurrence. Doctors recommended Lupron at that stage, but he decided to make many holistic changes, and decided to avoid ADT as long as possible for quality of life. When PSA started rising 2 years after that, it did so quickly and scan showed Ogliomets. He is now taking both Lupron and Xtandi and is tolerating both very well. We opted for Xtandi over Zytiga because we did not want to take the steroids required with Zytiga. According to everything we read and our oncologist, that is the most current standard of care for his stage. Luckily, he is working and insurance covers most of the outrageous $11,000 per month cost of Xtandi.

[Velohomme in reply to magcali]

Thanks for the info. 11K is truly amazing.

[Hidden]

Well...I was pt3bn1mo after my diagnosis and I'm on eligard and zytiga. G9 (4+5) and IMRT to pelvic areaand prostate bed.

Similar treatments as you but in a shorter period of time.

I think the adt +2nd line adt is not uniform for HS NM pca but is slowly being adopted.

[Velohomme]

I was successful in getting my doctor and insurance company to agree to Zytiga. It took some pressure on the insurance company but I think that is common: ins. co. says no, dr. challenges them, ins. co. says yes.

The cost per month is ~6.5k (I only pay $10 co-pay). (4) 250mg pills per day, 5 mg. of prednizone daily.

The effect on my PSA was dramatic. In 5 weeks it dropped from hovering at .24 to .027.

[Hidden in reply to Velohomme]

I'm assuming you meant 5mg prednisone. 50 mg is for people suffering allergic reactions

[Velohomme in reply to Hidden]

Yep. Edited. Thanks.