ADT Failure - Within 6 months

[Hazard]

I am still in a state of shock as I write this but here goes -

After salvage radiation in 2016, I had reduction in PSA in my first test (from 0.1 to 0.07) but PSA rose with each subsequent test, peaking at 7.5 in April 2017 immediately before I started ADT.

Specialist told me that ADT would get PSA down to 0.1 within 3 months. He also said that it should hold things at bay for 2-3 years.

- after 3 months PSA was still 2.1

- after 6 months (got my test result this morning) PSA is now 15.9!!

I also had a testo result. it measured 0.4 nmol/L (about 12 ng/DL) so this is nice and low. I am waiting on results of a DHT test (blood sample was taken 31 Oct) - there are no labs here in Melbourne that test DHT and blood has gone to Sydney for analysis.

Before we start throwing more treatment at this, I really want to understand what is going on here. My PSA before RP was 7.8 (0.026 immediately afterwards) and this is now a record PSA. PSMA scam in April showed a single nodule in my pelvis, I don't have any other mets (well I guess this is now an incorrect statement). What other tests should I be looking at or is it best just to throw the kitchen sink at this now?

I know that many men here have extensive mets and much higher PSA but I also see that most people do respond to ADT for some period. I seem to have become carstrate-resistant almost immediately. Anyone else have this experience?

[YostConner]

I’m sorry ADT did not do more for you. Is chemo available early for you? One of our brothers in Brisbane found success with that approach. If not either Zytiga or Xtandi may be next for you.

[Hidden]

First of all, don't panic. You still have a lot of treatment choices at your disposal. You might want to discuss chemo with your mo. It took my psa from 850 to 0.07. I know, I know it freaks you out, but hey you have a long way to go. Regroup and plan your next attack with a level headed attitude. The shock will wear off and you will be rationalizing the situation in no time. It's roll up your sleeves time and get to work at kicking this stuff down.

[Hidden]

Sorry you didn't have a good response to ADT. You are right for wanting to know why before just throwing treatments at it. It's important to find out a spoon as possible.

I'm not a doctor, but I know there are reasons why that can happen. One possible reason is that the prostate cancer has neuroendocrine differentiation. That's a type of cancer cell that has no androgen receptor and will not respond to androgen receptor based treatments such as Lupron, Zolodex, etc. If that's the case, it also won't respond to secondary ADT agents such as Xtandi or Zytiga.

According to an article I read, this type of cancer most commonly evolves from preexisting prostate adenocarcinoma .... And while it rarely arises de novo, the amount of neuroendocrine differentiation of prostate adenocarcinoma increases with disease progression and in response to androgen-deprivation therapy.

“Neuroendocrine prostate cancer does not express the androgen receptor and it's considered clinically hormone refractory. With the introduction of new highly potent androgen receptor-targeted agents into the clinic, such as abiraterone acetate, treatment-related neuroendocrine prostate cancer is becoming an even more important disease to recognize.”

Beltran and colleagues have written that treatment-related neuroendocrine prostate cancer should be suspected in patients with castration-resistant prostate cancer who experience rapid progression with a low serum PSA, especially in the setting of potent androgen deprivation therapies.

Have you had a biopsy? With a biopsy of the cancer, these cells can be seen with a microscope. There is also a substance called Chromogranin A that is produced by these cells and can be measured in a blood test.

The target of these cells when they metastasize is often organs and/or soft tissue (EX. lungs, liver), not the typical bone metastases. So if it were me, I would want to look at those areas specifically.

There is also the possibility of mutations where the cancer cells are no longer sensitive to androgen-based treatments. A common mutation is the ARV-7 splice variant. These can often be detected with genetic testing (blood test).

In either of those cases, the likely direction for treatment is chemotherapy, probably Docetaxel and/or Carboplatin.

You should run everything by your doctor and discuss it with him/her.

Let us know the outcome and we all wish the best for your treatment. We'll be here to support you.

[Hazard]

Thanks everyone for kind responses.

I saw my onco today. He is as surprised as I am by my result. He is re-staging my disease - more PSA tests next week to confirm the level, plus CT scan and bone scan. After this he will discuss treatment - he didn't want to give too much away at this time but said that treatment will depend on whether any mets are found.

Oh and he filled me up with more Zolodex. I said that Zolodex is having zero impact, PSA double time was 1 mth before ADT and its still one month. But he would not be swayed

[Chubby42]

Hi Hazard your figures are similar to mine if been offered chemo and ADT first up treatment if just had my 6th chemo & PSA is down from 8.7 to 2.5 my ADT is Zoladex now 3 monthly.

My Gleeson score was 4+3 PSA doubling time of 4 weeks. Im also worried about my ADT failing early but hoping for 18+ months.

Good luck m8

[vandy69]

Good Morning Hazard,

If last scan was April, it appears that you need the full complement of new scans before beginning this next battle.

PSMA scan and Axumin scan are the latest, greatest for soft tissue mets, but not sure if they pickup bone mets. Sodium Fluoride F-18 PET/CT was the gold standard for bone involvement.

Your team needs to find the source of this rapid jump in PSA to plan the right combination of drugs and/or chemo. The good news is that you have many weapons left to fight this war!

Best wishes. Never Give In.

[Hazard in reply to vandy69]

Thanks Chubby and Vandy. Interesting times ahead for all of us.