Possible castrate resistance already?

[Stumpgirl]

My newly diagnosed father just has his first follow up appointment. He started Lupron and casodex in May. His bone pain has persisted. The ro seemed to think there might be explanations for this but the mo was less hopeful. He said my dad's symptoms should be alleviated and that if the Lupron isn't working, this changes things dramatically. They drew blood today and will retest his psa. We get the answers tomorrow. Four months ago, we didn't even know he had cancer. I feel so hopeless right now

[Hidden]

Sorry you have to be here, but glad you found this group. In order to see if your father is castrate resistant, you have to make sure he is a castrate by checking his testosterone level. It should be 20 or less. It takes around 3 weeks to reach that on Lupron so he should be there. If not, he may need to try something else.

I'm assuming they already know through a biopsy that his cancer is the hormone sensitive variety. If not, Lupron will not work, only chemo. Luckily most prostate cancers are hormone sensitive.

Also should have his Alkaline Phosphatase level checked (blood test). His Alkaline Phosphatase level should be going down down if his bone mets are improving.

Did he already have any CT, T99 bone scan or PET scans done? If so, he could get more imaging and see what's going on there. Those are few things I can think of, but there are a lot more knowledgeable people here who can probably add more.

Keep us posted and remember we are here to help and support our prostate cancer brothers and sisters in this fight.

[Stumpgirl in reply to Hidden]

They did a full blood panel today and will call us with that information tomorrow, apparently. When we first met with the mo, he said that my dad was "hormone naive" because they did not know what his response would be. His cancer was found stage 4 and its aggressive. He got his first Lupron shot in May. The mo said he should be alleviated of his symptoms and he is having ongoing pain. Our concern is that he loses time with not being responsive to the Lupron. My father seems very confused. He can't identify where the pain is- just that it's all over or one day it is in one area and the next, somewhere else. I don't know if he's scared and trying to tell them what he thinks they want to hear or if the medications he is on is making his brain foggy. We just need to catch some sort of break.. the news consistently gets worse

[Hidden in reply to Stumpgirl]

Where are you located?

[Hidden in reply to Stumpgirl]

My bone pain was exactly the same way, it seemed to be moving around my body although the lower back pain was constant. But it got better after a month on Lupron. Have they done any imaging and if so what kind?

[Stumpgirl in reply to Hidden]

We are in cleveland and he's at the clinic. Depending on the results of the psa tomorrow, they'll order further imaging. We just hoped so badly he could get a few years out of the Lupron

[Hidden in reply to Stumpgirl]

The Cleveland Clinic has an excellent reputation as far as I know so I think you are good hands.

It doesn't make any sense to me that his cancer is hormone sensitive, yet Lupron is not having any effect on the cancer from the beginning. Did they do a biopsy?

When you get his testosterone levels you'll know whether Lupron is working. I think there have been cases where it didn't work and something else had to be used.

I'm doing early chemo in addition to Lupron in accordance with recent trials that showed an increase in life expectancy for hormone therapy + chemo. I would recommend considering that too.

[Stumpgirl in reply to Hidden]

I'm not sure. My parents were relaying the biopsy results to me in layman terms but never were we told whether or not the cancer was hormone sensitive . I know he has a very high Gleason score and multiple mets- lumbar spine, femurs, a couple of spots on his ribs. We were told first line of therapy was the casodex and Lupron. We would be adding zytiga or chemo soon after. The doctor seemed very concerned that my dad's pain has persisted and this is why he thinks the Lupron may not be working. If the numbers are reported to have gone down tomorrow, he is adding zytiga and doing more scans to see if there are fractures. If it has not gone down or has risen, they will move to chemo right away and do more imaging to check for disease progression. I wasn't aware that a biopsy could show if he was hormone sensitive. We will know more tomorrow

[Hidden in reply to Stumpgirl]

Just want to clarify, there is no test to definitively prove that the prostate cancer is hormone sensitive. But the biopsy shows whether the cancer is neuroendocrine which has no androgren receptors and is therefore not sensitive to ADT (androgen derivation therapy). That's the standard term for treatments that either lower testosterone levels (Lupron and others) or block the cancer's androgen receptors in one way or another (Zytiga and Xtandi). Only around 2 or 3 percent of prostate cancer is neuroendocrine from the beginning so it's unlikely, but possible. But I'd say it's very unlikely they didn't check that before starting him on ADT.

My doctor explained this to me and told me they needed a biopsy before they started treatment. That way they could make sure they were giving me a treatment that at least had the possibility of working.

Sometimes there are gene mutations in the cancer such as BRCA2 which make the cancer quickly become resistant to ADT. You can find this out with genetic testing. Gene mutations can often be exploited in what's called "targeted treatment."

[AlanMeyer in reply to Hidden]

Minor correction.

If I understand it correctly, Zytiga's main mechanism of action is to lower testosterone levels. It works entirely differently from Lupron and reduces T far more than Lupron or than physical castration. The Wikipedia has a technical explanation in the article for "abiraterone acetate".

[Hidden in reply to AlanMeyer]

You are correct. Thanks for sharing that information, I wasn't aware of it. I just read Zytiga can reduce T levels to around 1 which is amazing. I thought it blocked the receptors only.

[Hidden in reply to AlanMeyer]

Yes, our ONC said it reduces hormones coming from adrenal glands

[anya6 in reply to Stumpgirl]

I feel you. My dad found out he was Gleason 10 in November. They started casodex Lupron and chemo. It was a tough few months but his numbers were getting better. Then after the last chemo they went up and we were trying to figure out whether to do xtandi or zytiga bc the doctor thinks he is casodex resistant when they found something in his liver. Liver trumps so now paused everything to biopsy and see if prostate has spread or it appeared on its own.

The hardest part is the up and down. Every little piece of good news seems to be overshadowed by bad news. Goal at the moment is to eat well and move around. Tough since he is nauseous and exhausted. i think keeping him occupied and staying healthy is the best you can do while waiting for results. And also doing scans often and really paying attention to how the pain is changing. He started to have a few new pains and lose his appetite. This combined w a Slight change in some of his test scores, signaled other issues.

Best of luck!

[Stumpgirl in reply to anya6]

Thank you and best of luck to you and your father as well. You're right about the ups and downs. It's hard to remain hopeful and it's so hard to see my father unable to live the life he was accustomed to just a few short months ago. I'm thankful for this forum. I'm able to access so much information I otherwise wouldn't. I'll be praying for your family

[rococo in reply to Stumpgirl]

If their is extensive bone mets and pain firmigon would be the drug of . positive effects are immediate as castration is complete with no flair. Cleve clin? Pray to god you find a doc thats sensitive your dads needs. Rocco

[Stumpgirl]

I know he had a biopsy but was not aware of this. I'm feeling genetic testing is probably important though it's not being recommended. They're saying chemo would be next

[Hidden in reply to Stumpgirl]

This is just my opinion, I'm not a doctor. But it seems to me that if you are not responding to the treatment, there's a reason why and you need to find that out if possible so you can determine the best course of action. Different types of prostate cancer need different types of treatment. Otherwise it's a trial and error process and as you said earlier, time is not to be wasted. I think in these cases where the response is out of the ordinary, it makes sense to look more closely at the cancer and see what the genetic makeup is.

[Sisira]

This is stage iv most aggressive PCa. Still hormone sensitive. But remember PCa is heterogeneous meaning there are hormone insensitive cancer cells - most dangerous when they take the upper hand, non stoppable. My advice is, this type of cancer should be given a hard punch as early as possible taking into consideration all types of cancer cells. Hormone therapy alone can't do that job. Early chemo therapy combined with ADT ( Lupron ) is what I am talking about. The recently concluded SAMPEDE Trial too has confirmed this and gone to the extent the combination can be even early chemotherapy combined with Zytiga ( Arbirateron ). You can discuss this protocol - systemic ( full body ) and cytotoxic ( killing cells ) with your Oncologist.

Wish you and your dad all the strength to fight against this beast.

Sisira

[Stumpgirl in reply to Sisira]

Thank you very much. If they see that his psa is reduced, they will be adding zytiga. If it has stayed the same or increased, they will go straight to chemo. He seemed to have a very very short window of pain reduction after beginning the casodex and Lupron.. he has to take oxy and patches to deal with the bone pain currently which is what has everyone concerned. We were just very hopeful he would have responded well and that he could take the zytiga and skip chemo but it doesn't sound like that is going to be the case.

[DFZ4835 in reply to Stumpgirl]

Don't skip the chemo. It's one of the best, if not the best, cancer killer available. The chemo is recommended with ADT early on in treatment. This gives you the best long term results and extends life expectancy by several months. Chemotherapy has a bum rap. It is not as bad as reported by the press. I am on my second round of chemo. The first was shortly after I was diagnosed with stage 4 prostate cancer with bone mets to numerous to count. That was 6 years ago. Chemotherapy wasn't bad then and isn't now. Everyone has there own reactions to any meds including chemo.

I will pray for your dad and he's daughter.

Dennis

[Hidden in reply to DFZ4835]

I'm going to second this. I would really recommend early chemo based on the results of the CHAARTED and STAMPEDE trials. Early chemo showed a 13 month average survival benefit and 17 month survival benefit for those with higher tumor burdens. The reasons why I would recommend doing it now are:

1. It goes after any cells that are not responding to ADT

2. It's only an 18 week treatment and you can go on Zytiga after

3. Chemo is far less useful if done later when the cancer has evolved and there is more of it to kill.

I completely agree that chemo is getting a bad rap. The side effects are not that bad for what you are potentially getting back. I had to ask myself: If chemo was the only option available, would I do it? My answer was yes. But waiting until the end you only get 3-5 months benefit, so I decided I might as well do it now and get the most potential.

And now after 4 months of treatment with ADT and chemo, my PSA is .2 Of course there are no guarantees of future response, but why not give yourself the best possible odds?

[Sisira in reply to Stumpgirl]

Listen to Dennis one more time. Sequencing approach, that is you finish with one drug when it fails and start with another and start with a third one when the second one fails and so on... is an old paradigm. The modern more effective approach is the Multi-modal Approach of using strong combinations at the earliest instance to treat HSPC, CRPC and mCRPC to get the maximum survival benefit.

Look at all available options objectively.

All the best

Sisira

[Stumpgirl]

Finally some wonderful news.. my dad's psa has gone from 145 to 3.5 in just under 3 months.. now to figure out where the bone pain is coming from. Thank you all for your responses and encouragement

[Hidden in reply to Stumpgirl]

Fantastic! I'm so glad to hear! I know the bone pain can sometimes take a while to go down even with successful treatment. Did he get his Alkaline Phosphatase tested? If that's going down its a really good sign that the bone mets are subsiding.

[Stumpgirl in reply to Hidden]

Thanks.. we needed good news so badly . I hope the bone pain will be subsiding soon. They'll be starting him on zytiga asap. I just asked my mom to look at the bloodwork for those levels. We were not aware those were relevant.

[Hidden in reply to Stumpgirl]

Alkaline Phosphatase is one that's relevant if you have bone mets. Mine went from 600 at diagnosis to 72 now. 117 is the maximum of the normal range so 72 is well within the normal range. It's a very valuable indication because not all prostate cancer produces the PSA, but Alk phos is a fairly reliable indication when it comes to bone mets.