My husband and I are in shock after our visit to Mass General where my husband got bone and CT scans last week. (Due to pacemaker, he can’t get an MRI) From just a 4-5 mets last year, he now has many mets up and down his spine, in ribs, shoulders, pelvic bones.
As you can see from signature below, he resumed Lupron last year, and started Zytiga six months ago in February, 2019. His PSA dropped steadily. Throughout, Alkaline Phostophase (ALP) and calcium levels have remained well within normal range. The only abnormality has been a rise in liver enzymes in the last couple months but not outrageously off the charts. At first, our oncologist, Dr. Matthew Smith, said to stop the Zytiga entirely again then possibly resume it at a lower dose. (My husband had stopped it for two weeks a month ago, restarted, but liver enzymes were up again.) Dr. Smith said this late rise in enzymes four months in was a “head scratcher” since this kind of rise usually happens in the first months. (He was reviewing the blood test results and scans for the first time while we were there.)
Then he got to the scans. He studied them for a really long time—nothing ambiguous about them—new mets in many bones despite the current low PSA 0.64. He ordered the genetic test Guardant 360, which my husband had done after the appointment, results to come in a week. Dr. Smith then said it was time to forget the Zytiga plan and arrange to start chemo in October. All three of us were rattled. The subject of ALP and calcium didn’t come up. We only thought to recheck the numbers when we got back from Boston. They’re normal. How can this be?
My husband is going to ask some questions via the portal today. What about the normal ALP and calcium? Are any of the mets in viscera (liver possibly even though reports don't show anything?)? Continue Lupron? What else should my husband ask?
At dx my husband was high Gleason 9 with a low PSA of 3.38. But seeming “success,” after nearly three years of non-stop Lupron, then a resumption of it combined with Zytiga, was based on measuring PSA, not scans. The steady PSA decline since the Lupron restart then the Zytiga misled all of us into thinking the drug regime was effective. Has anyone out there experienced seemingly good numbers masking mets' progression? For what it’s worth, my husband has no unusual pains, just the typical ADT brain fog and fatigue. He’s been running, jogging, lifting weights, motorcycling, etc. thoughout.
SIGNATURE:
AS OF 8/21/19 Husband's prostate cancer history:
Husband 70 yrs (74 now)
pacemaker; Agent Orange 6-9/14: blood in urine; DRE suspicious
biopsy 11/14: G 9 (4+5), PSA: 3.32 high Gleason, low PSA, PNI involved
11/14: Lupron 33 mos
6/15: 9 wks IMRT
9/15: .14
1/16=.093
4/16=.079
11/16=.05
2/17-5/17=.05
11/17=.08
2/18 .20
4/18 0.98
6/18: 3-4 bone mets; 7/18 3.29
8/18 PSA 9.87 Lupron re-started
Zytiga/Prednisone started 2/9/19
2/28/19 PSA 4.02 (ALP=85; ALT-23; AST=30)
4/11/19 PSA 1.80 (ALP=68; ALT=22; AST=27)
5/28/19 PSA 0.92 (ALP=65; ALT=95; AST=67
6/14/19: PSA 1.26 (ALP=62; ALT=85; AST=50)
Zytiga 2-wk break
8/2/19: PSA 0.64 (ALP=57; ALT=159; AST=92 (told to resume Zytiga)
8/16/19: PSA 0.64 (ALP=62; ALT=173; AST=103)
Bone and CT scans done
8/20/19 VISIT: Scans indicate intensity of old mets but many new ones in spine, ribs, pelvis
"Kidney, bladder and soft tissue uptake within expected physiologice limits." Chemo recommended
to begin in Oct. Oh, 3-month Lupron shot given.
Thanks for slogging through. I hadn't posted new data for awhile, so it was time to
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spouse21
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It was one of these whirlwind visits where we and he were getting real-time information simultaneously. (Why don't some of these oncs read stuff ahead of time? This has happened here and elsewhere. We wasted time talking about a Zytiga plan due to elevated enzymes then it all went out the window after he--and we--saw the scans together. Then it was a whole other ballgame but the visit was over so fast, we couldn't think straight to ask the right questions.) The visit was a train wreck, frankly, but we wound up having a great lunch at a French restaurant and beaucoup wine despite the liver enzymes. We needed it
I agree. With low PSA and progression, I would get a biospy and check for Neuroendocrine since it doesn't produce PSA. With rising/high liver enzymes, I would also want to get imaging to see if there are liver mets since Neuroencodrine often goes to organs and soft tissue.
I would also agree with going to chemotherapy, possibly adding a platinum-based chemo if Neuroendocrine cells are found.
These are things you can discuss with your doctor. Wishing you the best with treatment.
Thanks, Gregg. Current scans say no mets in any soft tissue . . . yet. When you say biopsy, what gets biopsied? I think the Guardant360 gazillion-dollar blood test may have a lot of answers.
Anyone out there care to speculate why, with many bone mets, the Alkaline Phosphonate and Calcium numbers would be completely normal? I'll weigh in when our oncologist responds to that question, but it seems bizarre to us.
The type of testing you get depends on what you are looking for. The Circulating Tumor Cell (blood test) is good for genetic mutations such as BRCA1, BRCA2, ATM, and AR-V7 to name a few. Taking an actual tissue sample and looking at it under the microscope is needed to determine whether you have the neuroendocrine cells that don't produce PSA. I would want to do that so you can see whether adding a platinum-based chemo such as Cisplatin or Carboplatin would help. I'm guessing they will be prescribing Taxotere (Docetaxel) first line or Jevtana (Cabazitaxel) second line chemotherapy with the possibilty of adding the platinum chemo.
The good AlK Phos numbers indicate there is not a lot of activity in the mets, although they are still there like mine. I have very many mets and an Alk Phos that is currently 80.
Alkaline phosphatase is an insensitive indicator of bone metastases."
My *guess* is that slow growing metastases only raise ALP a little bit, less than what would be considered normal variation between people. Do you know what your husbands baseline ALP levels were years ago? (from a routine metabolic panel, for example).
For reference, years ago my ALP would be in the low 40s, shot up to near 1000 after diagnosis, and was last seen in the 30s. My last bone scan was much improved, but still showed some activity (the MO suggested that activity could be healing).
Not to nitpick, but the article linked is for renal cell carcinoma which forms osteolytic metastases primarily. ALP is more reliable as an indicator for the osteoblastic metastases most common in prostate cancer, although there are still some specificity issues. If you can rule out the liver, it becomes a lot more specific.
The bone-specific ALP is more specific since it doesn't include other places where it's made such as liver, intestines, etc.
This is a good topic of discussion and thanks to all for contributing.
Nitpick away! Just found it interesting that not all bone metastases result in super high ALP. The article you linked showed bone specific ALPs in the double digits with metastases, which may not get total ALP over 100, let alone above normal.
The article I linked has the same problem with including cancers that don't produce a lot of ALP. I'm trying to find articles specific to prostate cancer. I think that would be more useful for the discussion.
My thinking is if other cancers can cause bone mets without a large rise in ALP, then some prostate cancers can probably do it too (though this would be the exception, not the rule).
I agree, some prostate cancers don't produce as much but as you say it's the exception. The neuroendocrine types are more predominantly osteolytic although it's always mixed.
I think our ALP values will be useful as one marker, with limitations of course.
I get a little paranoid about it sometimes (along with all the other blood tests) At my last appointment, I pointed out to my doctor that my ALP had risen from 70 to 79. He said that's a normal amount of fluctuation between readings, could even be caused by what you happened to eat. It's easy to read too much into these tests.
It's very easy to be paranoid, especially since some of my lesions are lytic! The thing I'm trying to learn from my MO, and may also be worth pointing out to spouse21 , is that not everything that shows up on a scan has to be cancer.
A quick Google search shows that arthritis can cause lytic lesions that show up on a bone scan, and may even raise ALP as well. I'm not suggesting all my lesions are arthritis, but the lytic one around my sacroiliac joint that acts more like an over-use injury from running probably *is* (or at least started as) an over-use injury from running. Of course, the cancer could have opportunistically moved in as well, after everything was already damaged and inflamed.
The whole thing is really complicated. I think we are all looking over our shoulders constantly. It's hard not to think: Everything is cancer.
I have some pain in my neck (besides having cancer). My doctor ordered an x-ray and told me at the last appointment it was arthritis. I almost wanted to argue: Are you sure? Can you tell from just an x-ray? What if it's a new met?
He keeps telling me that with an undetectable PSA there is very little chance of progression, but still I can get paranoid.
This is a hard way to live, but we are alive and that's fantastic.
Not to scare or worry you, but because lytic mets are so rare in PCa, it's recommended to rule out other causes, particularly Multiple Myeloma. I suspect you already know this, but wanted to mention it just in case.
Actually, I didn't know that... >gulp< I've already had two cancer diagnoses this year, tell the Myeloma it will have to take a number and wait in line.
Wouldn't it be nice if there were a list of " absolutes" that one could rely on with this disease... Just when you think you are emerging from the woods you find another stand of trees...... So many times we get these unpleasant "surprises" when we thought things were progressing well. I , too, thought that ALP was a good indicator of bone mets.... one can never rest easy. Expect the worst and hope for the best sometimes seems the best course..
My husband is neuroendocrine, did 8 cycles of platinum based chemo, did well. Genome of tumor sequenced using Oncoplex, BRCA 2 gene found,somatic not Germaine. Started Lynparza last June, so far doing well. He has been on Lupron since July2017. He started on Zytiga but soon after dx he was discovered to be neuroendocrine. On top of that he developed Cushing’s Syndrome, extremely rare, now resolved thanks to his doctor who is a research scientist. Can’t say enough good things about him.
Great. Glad to hear he responded well to platinum chemo and now a PARP inhibitor. I think it's important that once our androgen-based treatments become ineffective, we get a biospy and CTC test to check for neuroendocrine PCa and somatic mutations. Your husband benefited from both.
I am not sure why they did not start Lupron on 4/18 after watching a PSADT of every 2-3 months for several cycles...11/17 to 4/18...that is water under the bridge...I am not convinced that Zytiga has failed him since he stayed at your new nadir of 0.64 despite taking a 2 week break...as for ALP and Zytiga--his ALP went from 85 to 62...ALP is a function of liver and bone function and despite LFT elevations--ALP wnl--I still think Zytiga is working--
If it were me, I would do the docetaxel and then retry the Zytiga with dexamethasone + Indomethacin, and Lupron, only because there are only so many drugs we have to choose from now, and if you can stretch out the time on Zytiga for another year or more, then go on to another drug, so much the better. We may have 2 new classes of drugs to add to Zytiga and the Lutamides in the next 5 years...Squeeze the time on these drugs to the maximum and wait for the Science... The Science is Coming !!!
Don Pescado
Bone-specific Alkaline Phosphatase has a higher senstivity and specificity for bone mets at .74
Thanks for all the comments, especially explanations about ALP. I'll have to dig back to see if my husband got some pre PCa ALP baselines. Husband did get biopsy for neoendocrine back when he got his first biopsy. Negative at that time. However, he's aware that unusual cancer cells can develop in neoendocrine later on. We'll bring up a resumption of Zytiga after the chemo with some of the add-ons. Right now, he's just on Lupron.
Unfortunately, there are some types of prostate cancer that don't put out much PSA or bone ALP. You were lucky to see the increase on a bone scan (they don't always show up there either. Only bone overgrowth shows up on a bone scan, not lytic tumors- which can be seen on CT). The Guardant360 analysis should tell you more and inform decision making.
Hi TA- Have you seen docs use Chromogranin A and/or Neuron Specific Endolase testing to determine neuroendocrine status or do you have any comments on their utility? Thank you.
Neuroendocrine status is easily determined by immunohistochemical analysis of a tumor. In fact, I just looked at a patient's IHC that was negative for CDX2, Chromogranin, Synaptophysin and Insulinoma Associated Protein. Sometimes they look for neuronal-specific enolase or CD56. None of the biomarkers are individually specific for NE cancer, so they have to be looked at collectively. Another hint is lytic bone mets seen only on CT, rather than the blastic kind that shows up on bone scans. It is a relatively rare occurrence, but increases (as a mixed type) over time. There are many very virulent types of prostate cancer that are not neuroendocrine.
Just want to pass on some information. I had a discussion with my doctor and he said markers such as CgA and NSE are not specific enough to detect neuroendocrine differentiation, but once neuroendocrine differentiation is confirmed, they can be useful as tumor markers in addition to or instead of PSA. Since neuroendocrine cells don't express PSA, it becomes less useful.
Some more general information on what is known as Treatment-Related Neuroendocrine Prostate Cancer:
An often under-recognized late manifestation of prostate cancer is the development of t-NEPC, which is considered a hormone refractory (AR-negative) subtype of prostate cancer.1 These tumors do not secrete PSA and should be suspected in a patient with progressive disease (especially visceral metastases) who has low or modestly elevated PSA. On the basis of autopsy series and other studies, t-NEPC may represent approximately 25% of late stage prostate cancer.9 Transformation from prostate adenocarcinoma to t-NEPC is believed to be promoted by androgen deprivation therapy and may arise as a mechanism of resistance....
Whereas biopsy is not always necessary or feasible in patients with late-stage CRPC to confirm the diagnosis, t-NEPC should be suspected in patients with CRPC who experience rapid progression with a low serum PSA, especially in the setting of potent androgen deprivation therapies. Patients with t-NEPC will likely not respond well to hormonal agents and may respond to platinum-based chemotherapy.
I t sounds like the most likely explanation is that there has been transformation to a neuroedocrine type clone.
This occurs in approximately 25% of patients with late stage castrate resistant prostate cancer and is an adaptation of the cancer to the treatment.(ADT plus abiraterone or enzalutamide)
My only query would be to check that the bone scan was the same radio isotope marker as the previous scans.
If the early scans were gallium scans and the most recent was a PSMA pet then that could explain the result differences.
I.E the mets have been there for ages but not showing bony changes.
If the mets are neuroendocrine but PSMA avid then maybe lutetium PSMA could be considered.
It is far less brutal than chemo.
Good luck sorting through the information quagmire.
I think you should pause and stand back to look at the big picture rather than get bogged down in complications. You have some time (all you need is a few weeks) to see if you can do some self-help before using sledge-hammers. Questions I would ask if face to face are:
Is the heart problem Potassium shortage related?
Is he over-weight in the gut area? This fat feeds the cancer.
Is he on a strict raw food diet and supplements to maximise his immune system? Low PSA can be from a poor immune system not doing many kills (PSA measures kills - you do not need exotic cancer cells to explain this).
Is he on ZERO sugar and wheat? A visit to the restaurant will grow a new crop of cancer cells in the few minutes of a sugar spike. NO treats! Nothing from a box, stove, or bottle!
What was his response to Vitamin C via IV? That could buy some more time and could be all the "chemo" he needs for a long time.
I’m so sorry you are going through this. You are going to a great hospital and obviously fighting this disease very hard. Have you asked about the LU177 trial or maybe look into going abroad for the treatment if you can not get into a study quickly in the US? Also, though it sounds like your doctor is thoughtful and cares, I think letting a different set of eyes may help. There’s so much being learned daily about the disease.
Another thought is an article one of the men posted on this site that I read when I get scared and down. “How Todd Seals Overcame Prostate Cancer Death”. I love this article. Never give up. Best wishes and hang in there!
Thank you all so much for the overwhelming responses, including from those speaking in the advanced PCa foreign language we may need down the road. We'll come back to this thread when we get the Guardant360 results in about fourteen days. We may need help interpreting our oncologist's recommendations. Stay tuned.
P.S. Oh, apologies for putting my title in bold caps--didn't mean to shout. I can't seem to undo it! I know that all of you respond whether something is in caps or all lower case.
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Slight uptick in PSA after 11 months of zytiga and lupron. 
FIRMAGON LUPRON NOW ZYTIGA PSA
Significant decrease in body odor if on Lupron and Zytiga?
Lupron and Zytiga working, PSA 1000+ to PSA 0.02
Welcoming good advice
