Castrate Resistant

[dhccpa]

I know that patients who were started at beginning with combo of, say, Lupron plus abiraterone acetate are declared castrate resistant when PSA rises in certain ways and/or progression is shown on scans.

However, for someone like me, who's been on Lupron only since diagnosis, am I not castrate resistant when Lupron fails? Without having had a second line hormone therapy?

My oncologist seemed a little shaky on his use of the term, and it could be impactful since castrate resistance allows a range of treatments that I'm asking about (in my mind without having to do Zytiga or Xtandi first).

Thanks.

[JohnInTheMiddle]

We'll look for any comment by Tall Allen. However I'm interested in what you mean by "without having to do Zytiga / Abiraterone" 😃

[dhccpa in reply to JohnInTheMiddle]

Without having to do them before (the key word) Provenge, Xofigo, chemo, (even Pluvicto if it is approved for use before chemo, or even if chemo fails). I didn't mean do without them forever; they can still be valuable after those treatments

[fireandice123]

That’s a good question. I was on Lupron only. Earlier this year my PSA started to rise even though my T level remained below castrate level. I’ve now added Abiraterone to the Lupron which seems to be working. I pronounced myself castrate resistant but I’m not sure my MO ever made that distinction. Now I’m not sure if I’m officially CR or not.

[dhccpa in reply to fireandice123]

ChatGPT answer seems to indicate after first line hormone therapy fails, which then makes you eligible for other treatments, including abiraterone or Enzalutamide.

[Mascouche in reply to dhccpa]

Abiraterone was initially given only to castration resistant men. I think it is only as of 2018 that it began to be used on castration sensitive men so maybe that muddies the line as to whether it is now considered first line or second line? Similar with Enzalutamide that was initially launched as only for castration sensitive men at around 2012 and also began to be used on castration sensitive men around 2018 too.

[dhccpa in reply to Mascouche]

Yes, that's what is prompting my question. I was diagnosed in 2018 and not put on doublet therapy. Most definitions I find SEEM to say castrate resistance occured when ADT (first line treatment) fails.

[vintage42 in reply to dhccpa]

"... after first line hormone therapy fails, which then makes you eligible for other treatments, including abiraterone..."

I don't think hormone therapy has to fail to be eligable for abiraterone. When I experienced biochemical recurrence, I started hormone therapy and abiraterone together as a doublet therapy.

[dhccpa in reply to vintage42]

True, but starting abiraterone may interfere with doing chemo next.

[vintage42 in reply to dhccpa]

Yes, I read that starting with ADT or ARPI makes the cancer cells senescent, which protects them from being killed by chemo later. Chemo apparently needs healthy growing "de novo" cells to work on. And yes, I missed the window for chemo because at almost 82, I was afraid of it.

Still, I don't see any eligibility requirements for Abiraterone. I started first line ADT about the same time as Abiraterone.

[Tall_Allen]

Castration resistance is defined as rising PSA above 0.2 in spite of ADT chemically (like Lupron) or orchiectomy. ADT never stops preventing testosterone production. Some men (for example, recurrent men) start taking second-line drugs (like abiraterone) when castration resistance sets in.

[dhccpa in reply to Tall_Allen]

Thanks. In my own case, my PSA low was 0.5. I've never had RP or radiation. I was wondering if, once Lupron fails partially, if immediately going to AA or Xtandi might interfere with also doing Provenge, Xofigo, or chemo. I just don't want to miss or delay a possible opportunity by starting 2nd line hormone therapy if that would conflict.

Also, some sites seem to define CR as happening when hormone therapy falters, without further clarification.

[Tall_Allen in reply to dhccpa]

When you become castration-resistant, all of those are possible, and Pluvicto after chemo. Lots to decide about sequencing and combining.

[Psahigher in reply to Tall_Allen]

what are your thoughts on any treatments after Pluvicto fails?

[Mw921000000 in reply to Psahigher]

I have this same question.

[billyboy3 in reply to Tall_Allen]

Will you please get back to me ASAP thanks

[Tall_Allen in reply to billyboy3]

Here's what I know:

prostatecancer.news/2019/12...

[billyboy3 in reply to Tall_Allen]

Thanks, I think I finally was listened to today but I lost seven months which I will not get back now!

[MJCA]

I read your bio. If your PSA is 0.97 there’s nothing to worry about being hormone resistant. I am surprised that your doctor has not recommended radiation to your bone mets. If you feel this is beyond the scope of your urologist, look for a competent MO to address your issues and concerns.

[dhccpa in reply to MJCA]

I need to update. PSA is now 1.92. I had at least 5-6 or more bone Mets prior to beginning Lupron in 2018. I didn't get into these latest changes because I was just asking a definition.

What is your understanding of when a person becomes castrate resistance? I gather there are differing impressions.

I'll update profile with latest PSA.

[MJCA]

I have been castrate-resistant for 6 years. What it means is that the usage of Lupron or orgovyx has no affect on the PSA. In other words, on ADT, your PSA continues to rise. One metric that is taken into account is the “doubling factor” or how fast is your PSA doubling. Normally nothing will be addressed until the PSA rises above the ceiling of 4.0. At that point in time SOC is to place you on a second generation hormone therapy such as Enzalutamide, Erleada, Nubeqa, Xtandi or Zytiga in combination with Lupron. I asked my MO “If I am castrate resistant, why am I still on Lupron?” The response was that even though Lupron has no effect on the PSA, it is still keeping testosterone levels low. This is important since testosterone is what feeds PCa. I hope this addresses your questions.

[dhccpa in reply to MJCA]

Thanks. Apparently, though, once ADT fails, there are choices besides adding second line hormone therapy. But that seems to be the majority course, perhaps because patients like it better than the thought of chemo, immunotherapy, etc.

You mentioned PSA rising to 4.0. I have understood that once it rises 2 full points above nadir (my nadir was 0.5), it's time to do something else, unless scans totally contradict progression. But I'm sure different docs tell patients different things, even within large medical institutions.

[MJCA in reply to dhccpa]

Read my bio. I have had this disease going on 19 years. I have been on most everything but Orgovyx, Xtandi, Jevtana and Keytruda. I feel like a walking encyclopedia of PCa treatments!

[mdiaz76 in reply to MJCA]

question for you, we just finished second go at Docetaxel (first was in 2017 -dx stage 4) Psa slowly rising. Dont want to exhaust all treatments, but Pluvicto seems to be on the horizon - how have you sustain post Pluvicto or are you still going through it? I believe it’s every 6 weeks for 6 cycles - my concern is having him have to stay away from grandbaby that lives with us for an entire week. That’s torturous for her.

[MJCA in reply to mdiaz76]

I am still on Pluvicto. I have two more infusions left. Yes, infusions are every six weeks. You are correct about your grandchild. Either you isolate your husband or harm your grandchild. Advanced cancer treatment is not easy. Personally, I just roll with the punches. Not more I can do.

[Mascouche in reply to dhccpa]

If you have had a curative intent treatment, and still have a prostate, then when the PSA rises 2 full points above nadir it indicates a recurrence. Maybe that is where you got that from?

[dhccpa in reply to Mascouche]

No, I was never curable. But the definition of castrate resistance seems to be slippery. ChatGPT seems to say when ADT stop working fully. However, one must still determine that has happened, and sometimes scans conflict with rising PSA.

I've never had RP or radiation.

[Stoneartist]

From my experience I find it useful to look upon the onset of castrate resistance as the onset of a tumour mutation which is not sensitive to ADT. I believe the original tumours which are castrate sensitive) and respond to ADT are all still there - though tiny and more or less dormant. Its the new type of tumour which is CR and can grow in an ADT environment - and we zap that with Xtandi or equivalent.

[Tacho in reply to Stoneartist]

Hello stoneartist

I started on Lupron, one shot then did Eligard (had my 2nd shot this past Monday) along with XTandi. My PSA levels in Deecmeber were 163 and now dropped to 1.22

No chemo or radiation yet I want to feel confident that my metastases is being zapped by Xtandi. Low back tail bone and pelvic lymph nodes. Oh yes, side effects of joint aches and uper and low back pain along with shoulder pain.

[Cenerus]

my MO told me that castration resistant used to mean rising PSA while taking a testosterone inhibitor like lupron, or after an orchiectomy. But in recent years it’s evolved to include rising PSA while taking both Lurpron and a second generation androgen suppressor like Zytiga. He said that you need to look carefully at how long ago stuff you read online was written. Things have been changing over the last 5 years in terms of the SOC and common practice among oncologists, and some online information is getting out of date. He thinks it’s a little misleading to call it castration resistant anymore. He thought that “hormone resistant” or “androgen blockade resistant “ are more accurate today because most MO’s prescribe two androgen inhibitors at once instead of in sequence.

[dhccpa in reply to Cenerus]

I hear you. I still see the term in current literature referencing ADT failure, so it's confusing. But I may want to do Provenge or chemo before I add another hormone therapy, so at this point I'm assuming failure of Lupron qualifies me.

[MateoBeach in reply to dhccpa]

You can declare castrate resistance if two rises in PSA and above 0.20 while on ADT, including Lupron or similar alone. Can be verified by total testosterone below 50 ng/dL. Does not require abiraterone progression. Go get the Provenge if you have at least one metastasis on scan. And any other treatment for mCRPC.

[dhccpa in reply to MateoBeach]

Thanks. My PSA never got below 0.5 over the last six years, so the 0.2 figure wouldn't apply to my case. Yes, I'm exploring Provenge as we speak. Not widely used, though, and seemingly used mostly by urologists, which seems unusual.

[Grandpa4]

why aren’t you on abiraterone already. Though SOC was both drugs early now.

[dhccpa in reply to Grandpa4]

I was diagnosed in 2018 and was started only on Lupron. Not sure when the doublet therapy reached this area.

[treedown in reply to dhccpa]

It happened around 2019 when I was dx. My MO was going to start me on Lupron only and after my 2nd opinion at SCCA they added zytiga. After recurrence on 2021 they restated me on both again, which is where I am now.

I agree there have been quite a few changes to SOC and imaging in last 5 years. Not all doctors stay up to date.

[NanoMRI]

Interesting discussion! Interesting read from two years ago suggesting definition may be outdated. Also interesting is reference to PSMA imaging. Over six years ago at 0.11 l traveled to Europe for Ga 68 and 'even better' Ferrotran nanoparticle MRI trial. Although Ga 68 was clear the nanoMRI identified five suspicious sites - correctly.

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

[jackwfrench]

Yes the SOC now is at least doublet therapy, commonly Lup and abi even if castrate sensitive. I am, and was started on both when PSA rose to 2.2 last year. My MO plans chemo if and when needed, no obvious deterent with the abi/Zytiga. Just my case.

[kiteND]

Considering that some treatments are only available if the patient is castrate resistant, one would think that there must exist a standard definition for "castrate resistant."

I am one of those stage 4 guys whose PSA has always been low or non-detectable. I was declared castrate-resistant when scans showed new tumors. PSA was and is still undetectable.

[JWPMP in reply to kiteND]

So am I to understand that you developed new tumors while undetectable? And they ordered scans while you were undetectable? My husband hasn't had a scan since 2021 and has been < .02 since then also. Thank you

[kiteND in reply to JWPMP]

Yes, it has happened more than once. Because of my history, I get a PSMA or Choline 11 scan every three months.

[JWPMP in reply to kiteND]

Wow, interesting. My husband is being treated at UCSF and they have not even suggested it. He even told them no treatment vacaction because he's hoping to avoid scans for as long as possible. I may have to ask his MO next month. Thank you again.

[Mgtd in reply to kiteND]

Boy that is a bummer. Do you know why that is?

[Professorgary]

I think you may be getting castrate resistant and hormone insensitive confused. Castrate resistant is when while on lupron your Psa rose and your T level was considered below castrate level which is 50. You can still be hormone sensitive so a drug like Abi which will lower T further could benefit. God bless.

[dhccpa in reply to Professorgary]

Thanks. Yes, CR may be here, and I'm having my first PSMA scan on 7/17 (that scan, however, should not change treatment whatever it shows).

Yes, I can start on AA at any time. I can do chemo anytime. But I'm exploring Provenge and is best to do it before chemo. By using AA, it could conflict with chemo by putting cells to rest. At least that's my understanding of the possibility. So I want to leave options open. My general take is that most references still indicate that once Lupron begins to partially fail, I will be considered CR.

[joedancer in reply to dhccpa]

Hey dhccpa. Yes, as Professorgary mentioned, my understanding is there is a difference between "castration resistant" and being no longer sensitive to all hormonal treatment. My feeling is that if I'm on leuprolide alone and my PSA begins rising significantly (and my testosterone is at castration level), I have become "castration resistant". It's the same idea as if had an orchiectonomy and my PSA then begins rising significantly. I happen to be in the situation where I have recently become "castration resistant". My PSA & alkaline phosphatase (I have bone metastasis) rose very high on leuprolide alone. Staying on leouprolide, I completed 6 treatments of docetaxel in May. My PSA remains very high. To date, I have not taken any of the more recently developed hormonal medications (abiraterone, enzalutamide, etc.). My oncologist & I have been discussing adding one of these medications and this will most likely be the next step for me when I see him next. Good luck with whatever further treatment you decide to go with.

[dhccpa in reply to joedancer]

Thank you. Interestingly, my alkaline phosphatase is below the low end of normal range and has been for over 3 years. Just the PSA slow rise is the issue so far.

[joedancer in reply to dhccpa]

That's good news about your A.P. Your A.P. being normal is an indication that the cancer, at least the bone metastasis aspect of it, is being held in check. Any rise in A.P. may be an indication of increased cancer activity in the bone. There are other reasons A.P. can rise (e.g. kidney issue), however, if you have bone metastasis, I would recommend keeping a close eye on A.P.

[dhccpa in reply to joedancer]

Thanks. Yes, I have been. I guess the PSA rise could be due to something else. Maybe the PSMA on 7/17 will reveal something.

[joedancer in reply to dhccpa]

Keep us posted.

[dhccpa in reply to joedancer]

Will do

[AlmostnoHope]

Yes you definitely are. The resistance means the Cancer cells are now making their own Castration resistant androgen.

[dhccpa in reply to AlmostnoHope]

I've had PSA jumps before that reversed, but not yet on this one. Perhaps my first PSMA will tell the tale on 7/17.

[Hidden]

I started Lupron and casodex for the initial testosterone flair and 37.5 mil of Effexor for the hot flashes... then went on to starting chemotherapy within weeks of the Lupron.

Did my Six Taxotere treatments and then Abiraterone Acetate and prednisone treatments about six weeks thereafter.

So far so good < 0.1 PSA

.

[dhccpa in reply to Hidden]

That's great