Another case of Rising ALP

[cbgjr]

Hello all,

I read with a lot of interest the two recent posts about increasing ALP numbers. Such is the case with me.

Dx in late 2011, Had RP in 2012, then SRT, then Lupro+Exgiva, and then Provenge this past spring. I showed the BRCA2 gene mutation in samples of the prostate tumor. I have many bone mets and in some lymph nodes

This summer had 6X Taxotere infusions, and PSA dropped from 78 to 15 in the process, however towards the end of the chemo treatment it had gone back up to 22.

Started Zytiga around Oct 10, and the PSA dropped to 4.8 but looks like it's levelling there.

The most worrisome part for me is that the ALP (which used to be steady around 80 about 5 months ago) has been recently increasing since about the time the chemo started (May), and now it is rising almost vertically if you plotted a graph. The other liver function tests showed normal, so that's not it. Had biopsy of LN to rule out NEC.

Bone aches are gradually increasing, but not enough for pain meds.

My MO doesn't appear overly concerned, said that the PSA is the thing to track. I have recently met with two doctors from MSK who also do not appear to be as concerned about the ALP as I am. the advice was to do another bonescan in 3 months (or sooner if pain increases), to look for NEW mets. I guess the old ones always keep showing up. However, one of the MSK docs, who isa PCa specialist, said that I would qualify for PARP-inhibitor trials when and if Zytiga stops working. My question is, is it really working if the PSA is far from <1 and the ALP is now going >400 and rising fast?

Has anyone gone thru a similar situation and what was the outcome?

Thanks in advance!

CG

[cbgjr]

thank you Nalakrats, I'll read up on Check Point inhibitors so I can bring up that topic... not sure they did Chromogranin A blood test for NEC, I thought just the LN biopsy was done to rule that out, but I'll ask that too. thanks again

[Tall_Allen in reply to cbgjr]

yes - you are right - if you'd had neuroendocrine disease it would have been picked up when they biopsied your lymph node, which is the best test there is. Neuroendocrine is a rare condition - I don't know why some people always seem to bring it up- it only causes anxiety. Checkpoint inhibitors have so far been unsuccessful against prostate cancer. A PARP inhibitor is a better hope for you.

[cbgjr in reply to Tall_Allen]

thank you. I'll be meeting with MO next week. I'll ask him what the criteria should be for determining if Zytiga is working or no. If it my PCa not NEC, then what's the explanation for the ALP rising so fast, and how long to wait before doing something different.

[Tall_Allen in reply to cbgjr]

You have been misinformed. Bone ALP does NOT rise rapidly with neuroendocrine PC. It is an indicator of osteoBLASTIC activity, whereas NE cancer is osteoCLASTIC. Those who are alarming you about this do not know what they're talking about.

[podsart in reply to Tall_Allen]

I think the osteoblasts (add bone cells) and osteoclasts ( remove bone cells) ,which I think, in normal bone tissue the osteoblasts replace the cells the osteoclasts remove in a balanced action.

It would be really helpful if you could provide any links regarding the osteoclasts action you refer to for NE Pca specific activity.

Then in PSA sensitive Pca bone mets, the osteoblasts dominates, so bone mets are formed by PSA sensitive Pca , which leads to rising ALP levels?

[Tall_Allen in reply to podsart]

Acinar adenocarcinoma prostate cancer is a better term than PSA sensitive (some kinds of acinar PC don't put out much PSA.)

There are 2 types of bone mets - lytic or blastic (or a combination of the two). "Lytic" means that the bone is eaten away by the cancer. It is characteristic of neuroendocrine cancers and many other kinds of cancer (e.g., many lung cancers). "Blastic" means that the cancer causes the bone to get overgrown. It is characteristic of normal acinar adenocarcinoma prostate cancer and most breast cancer. Whether the bone is eaten away or overgrown can be detected on a CT. Certain biomarkers and other imaging, like bone alkaline phosphatase, bone scans and sodium fluoride PET scans also only detect bone overgrowth.

[podsart in reply to Tall_Allen]

Thanks

[tango65]

This is information about the incidence of small cell neuroendocrine prostate cancer. It is more frequent than expected.

cancer.gov/news-events/canc...

ncbi.nlm.nih.gov/pubmed?ter...

[cbgjr in reply to tango65]

thank you

[Hidden in reply to tango65]

Thanks, here is more from one of the researchers in this:

Neuroendocrine prostate cancer is a high-risk, lethal subset of disease, often referred to as representing only two percent of all diagnosed prostate cancer. In fact, though, it probably occurs far more often because the disease is not recognized as different from metastatic castration-resistant prostate cancer.

That was the word from Himisha Beltran, M.D., assistant professor of Medicine in the Division of Hematology and Medical Oncology at Weill Cornell Medical College, speaking at the Chemotherapy Foundation Symposium, as reported in Oncology Times.

Men rarely undergo biopsy of their tumors once those tumors have spread to bone or soft tissue regions of the body, Beltran noted. So while only a few prostate cancers are diagnosed originally as neuroendocrine prostate cancer, many cases that develop after adenocarcinoma has evolved into neuroendocrine prostate cancer go undetected. She estimated that as many as one quarter of patients who are dying of prostate cancer are dying from treatment-related neuroendocrine prostate cancer.

The clinical features of the disease include frequent visceral and bulky soft-tissue metastases and limited duration of response to both hormonal therapy and cytotoxic chemotherapy.

Source: meyercancer.weill.cornell.e...

There is a debate about the terminology for this kind of cancer. While it does share morphology with Neuroendocrine Prostate Cancer, there are also differences. It's a complicated subject and so far what to call this has not been resolved.

More on that subject:

“Neuroendocrine prostate cancer” is also debated as an appropriate term to describe this clinical phenotype, as the term is currently not well defined and implies that small cell carcinoma or a predominantly neuroendocrine histology must be seen on biopsy, when it is clear that many cases with this clinical phenotype do not demonstrate classical morphology or immunohistochemical profiles (ie., chromogranin, synaptophysin, neuron specific enolase). Additionally, neuroendocrine features or immunohistochemical expression can be seen in prostate cancer that does not show such aggressive behavior (i.e. prostatic adenocarcinoma with paneth-cell like differentiation).

clincancerres.aacrjournals....

[cbgjr]

Thanks everyone for all your suggestions and valuable insight.

Upon further researching, I came across this article:

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

this is the gist of it:

"Results

Thirty-nine pre- and 45 post-chemotherapy patients with a median follow up of 14.0 months were analyzed. ALP-Bouncing can be observed very early during therapy with Abiraterone. ALP-Bouncing is defined as rapidly rising ALP-levels independent of baseline ALP during the first 2–4 weeks of Abiraterone-therapy with subsequent equally marked decline to pretreatment levels or better within 8 weeks of therapy, preceding potentially delayed PSA-decline. In univariate analysis failure of PSA-reduction ≥50 % and failure of ALP-Bouncing were the strongest predictors of progressive disease (p = 0.003 and 0.021). Rising ALP at 12 weeks, no PSA-reduction ≥50 % and no ALP-Bouncing were strongest predictors of poor OS, (all p < 0.001). Kaplan-Meier-analysis showed worse OS for rising ALP at 12 weeks, no PSA-reduction ≥50 % and no ALP-Bouncing (p < 0.001)."

So I guess I have to wait until 8-12 weeks from start of Zytiga treatment to see which way it goes. But as I understand after reading the article, an initial sharp ALP bump together with a PSA drop of >50% could actually be a good sign.

I think that it is amazing that none of the health providers to whom I expressed my concerns offered this (probable) explanation to me. Oh well.

CG

[tupstar2000]

Hi,

My dad had a bone flare and alp rise from 300 to 1000 just after initiating the hormone injection, the alp then started to decrease.

His last blood test which is the first after finishing chemo shows another big drop in psa from 1.6 to 0.2, however a rise in alp from 91 to 139! I can’t find any articles on this! Just that alp rise after chemo and then stabilized for a couple men!

I’m just hoping it’s normal!

[DSEE]

I agree that oncologists are never concerned when that level increases.

All we were told is that the level is high because of bone disease.

Mine was 615 last visit from 74 at diagnosis.