Good day to you wherever you may be. I'm seeking to get feedback on folks' experiences with lytic bone lesions specifically.
As background, although bone metastasis with APCa is very common, lytic bone tumors (i.e., destructive type) have been touted in the literature as being less common than sclerotic/osteoblastic tumors (i.e.,hardening or depositing type). In fact, lytic tumors have been labeled as being "rare" - and there is no better group to reach out to in order to get a real-time sampling (albeit qualitative) to test this apparent truism.
Bone tumors have been identified in my spine (C3 and L4), all over my rib cage (left, right, and center), margin of the right hip, distal left femur, and peppering my lower left and right legs and feet. Interestingly enough, my tumors appear to be primarily lytic in nature, a theory supported by the fact that my blood alkaline phosphatase (ALP) levels have NEVER been high since my diagnosis in September 2016 (PSA 134) - at that time, at the beginning of my ADT, chemo, and focused radiation for my spinal tumors, my ALP was 72 IU/L (with a "normal" reference range of 46 - 116 IU/L).
Since then, my ALP has been consistently lower than normal, in the high 30s or low 40s (possibly an indicator of some liver stress, although my liver numbers appear okay). I am currently on Lupron, Zytiga, and Xgeva. Each of my subsequent NaF PET scans since 9/17 (chosen because of increased affinity of NaF to lytic lesions) have shown "interval stable" results. Good news as long as it lasts!
Like so many here with bone metastases, I spend a good deal of time doing research and becoming educated. For those interested, here is a good reference:
I have a couple of basic questions: Am I missing a treatment opportunity associated with having a tumor burden that is primarily lytic in nature? And, in contrast, am I missing a potential threat indicated by this type of tumor burden?
I have some thoughts, but would like to hear from the group. Thanks in advance. - Joe M.
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And you win the first kewpie doll, Greg. I saw this exact article last summer and frankly it's been gnawing at me a bit as I mulled my ever-low ALP even as a steady PSA rise in the fall of 2018 led to me being put on Zytiga this time last year.
The marrow biopsy seems to be a logical step that I've been avoiding since reading that article; after all, I've been doing well....but if my bone tumor burden isn't associated with APCa (i.e., the PCa is still encapsulated), I'm possibly putting myself at risk with long-term ADT.
I think it unlikely to be something other than APCa....after all, the tumors are stable under ADT...but, then again, ADT affects many metabolic pathways... this is certainly curious.
CBC is all normal, although some components tend towards low normal or just a bit lower. This trend in CBC reads has been consistent since coming out of chemo 3 years ago.
Good that your CBC is in range or close to it. ADT tyically causes anemia so that might explain some of numbers that are low. I'd be concerned if the numbers keep going down but as long as they are stable, that's good.
I would probably get a biopsy and check for neuroendocrine cells or other possible causes of the lytic mets. A biopsy would also give you the opportunity to do molecular testing for somatic mutations. That might open up a treatment option for you down the road.
I've had a bone biopsy and it's wasn't bad.
What is you current PSA? How long have you been on ADT?
This week's PSA: 0.35. ADT since September 1, 2016... abiraterone to take the t-spike out of the first round of Lupron, then Lupron-only until February 2019, when a 6 month rise to PSA of 1.72 led to the decision to include Zytiga. PSA fairly consistent in the last year fluctuating up and down around 0.28...so while 0.35 does indicate a rise, I will have to wait to see if this is a true trend.
I thnk it's unlikely you have much if any neuroendocrine PCa with a PSA that low. Neuroendocrine PCa is a mix of PSA and non-PSA producing cells so you still have some PSA. Plus you have had long effective times on androgen-based treatments. You didn't mention visceral mets either so I'm guessing you don't have them.
I would still do a biopsy just to make sure and do the molecular testing.
Nope, no visceral mets of any extent...a couple of slight indications, but those completely disappeared with chemo, leaving only the bone mets for these last 3 years.
Agree...posting to the group now for biopsy referrals in the Denver, CO area. Thanks, Gregg.
I had a mixture of mets. I wouldn't say having lytic mets is rare, but usually even a lytic met will have some offsetting blastic activity and thus raise ALP and show up on a bone scan. It's your apparent lack of any blastic activity that I believe to be truly rare.
I can't comment on the treatment implications, but would opine that xgeva is very important in your case.
And you win the second kewpie....the continued low ALP is a puzzler...I would theorize that any mix of mets should at least put me into a high normal range for ALP even if there is some metabolic crash occurring elsewhere like my liver driving ALP down. But this liver crash doesn't seem to be occurring and numbers are fine, e.g., BUN is normal, albumin/globulin ratio is normal, etc.
And, yes, I am a supporter of Xgeva (btw, I have found nothing to indicate that Xgeva bombs ALP, but...?). In fact, I tested it out by slipping on the ice in my driveway and falling HARD on my wrist and arm....all intact but for a partial shoulder separation! I felt this was a clear victory but, alas, my wife did not see the clear value in this field test of my bone strength!
Thanks for the reply, Tom. And I read your post on your new challenge...good luck, brother. - Joe M.
Not a bad idea to have a biopsy. Lytic metastases are a common feature with neuroendocrine Pc, but not necessarily. I hope you are taking a bone strengthening agent.
Thanks for the reply, TA, although contemplation of neuroendocrine PCa is a nasty business indeed. It's a potential development that all of us with APCa should keep in mind.
Do you have any other insight into what appears to very low ALP other than a predominately lytic tumor profile?
Without intending any disrespect, I truly love that you are like the computer from Star Trek, TA! Fact without speculation.
I was fishing for a "In 2018, a Johns Hopkins study showed correlation of low ALP with....etc..." example. I have found nothing specific myself other than what gregg57 found.
Ha ha ha...ha....lets start calling Tall Allen "Commander Data" Just the facts..Man.
Lower levels of ALP indicate that not much healing/rebuilding of bone is happening.
Lytic lesions only corrode the bone tissue BUT does not cause rebuilding of bone and therefore the fracture risk is higher in lytic lesions. Bone builders infusions are needed in case like yours.
What was your initial PSA. Neuroendocrine cells do not churn out much PSA.
Also, If your AST, ALT. Albumin and LDH are are all within normal limits then, your liver is fine.
agreed....is Nalakrats then the Counselor Deanna Troi! Who here is Worf, I wonder....?
Intitial PSA 134...so, in hindsight, given the numerous mets, this reading may or may not be "low" in the context we are discussing... What gets me is the unrelenting nature of NE PCa - NE cells lack androgen receptors! How could I have been floating through traditional ADT without seeing something going astray?
It seems unthinkable that I would be so lucky. While I changed my diet and lost weight and limit meat and dairy, I still have those in moderation. I train routinely....and hard. I do not avoid weight training, strenuous hikes, mountain bike rides, etc.... and on the last two I've definitely taken a tumble or two. And all of this with a (technically) broken neck at C2 (found out on a roller coaster)... Oh, and I fell on my icy driveway - hard - a few weeks ago and nothing but soft-tissue damage. I am not brittle. QED.
Even as I write today, nothing has really changed. I think it was one of your recent responses, LearnAll, to someone's ALP level that got me thinking about this again... for so long, I was only looking at "Hey, great, ALP low..." then it became "Hey, um, great?, ALP low...", and now "Hey, WTF, ALP low!" ....
I was fortunate enough to get Provenge last summer, and that's the only other outside factor that I can think of that may bear on this mystery. I believe a biopsy is in my future to gain more data and rule in/out NE.
I'll have to run another post to get recommendations in the Denver, CO area. While I like my MO and cancer center, by design they are a Goodyear or Firestone and not a dealer mechanic, if you take my meaning.
An experienced Radiologist can recognize Osteolytic and Osteoblastic lesions on simple ,plain X rays. The characteristic of Osteoblastic lesions is cobblestone appearance with mixed white areas of sclerosis. Have you confirmed that your lesions are osteolytic ? Do they show clearly lytic type in imaging As for neuroendocrine tumor, I am still not convinced that it is in fact NE tumor...At least it did not start as NE tumor as PSA 134 is pretty high for that. Need more confirmation.
Agreed, and as I said...It's a Goodyear versus dealership analogy with respect to my MO facility. In those "early" days, my treatment was very straightforward and I didn't put a thought to NE or another pathological process in light of the 134 PSA...this is all poker game statistics and ADT + chemo + radiation was the hand I was going to play regardless of the provider. The addition of Zytiga last year was also a very straightforward play.
Now I'm looking at details in a different light, and the whole lytic v. blastic + low ALP issue needs to be resolved. Thanks for responding, LearnAll.
You should make post about that rollercoaster ride and the drive out west . What a way to find that you had pc . Dam I’m sorry I don’t have any answers . I just want to wish you well in this Hellish scenario .... keep doing good things.. that ice can be a killer . Take care brother.😎
I'm just glad I DID find it..I thank that roller coaster ride every...well, not every day...but frequently. It doesn't take but a few minutes reading the posts here of those dedicated men and women researching academic articles for all of us to know that APCa is one sneaky SOB....and I wouldn't have known until it was too late.
Now that I know that my cancer can run along without triggering an ALP response that I can use as early warning is an eye opener...and one I should have picked up on a couple of years ago. Oh well, live and learn.
Enjoy the desert, Brother. Even though winters are more mild here on Colorado's Front Range, I think I'm reaching the end of my tolerance of them!
My wife makes me gear up and take a phone to go to the mailbox now.... all 40 feet of the trip....
She’s just looking out for you....make the move to prescott . Mild winters and great the rest of the year....I’m glad that you found out also . You were one tuff cookie , still are .. I’m shocked as I log in each day and see the member numbers shooting upwards .. Apc is a sob that no one has figured out .. yet.. peace ✌️
"How could I have been floating through traditional ADT without seeing something going astray?"
Right. Long and deep responses to ADT are not likely with significant NE PC. Neuroendocrine Differentiation is usually a late stage development, generally after a long period of succesful treatment with androgen-based treatments. Typical symptoms are: short response to ADT, visceral mets, and often lytic bone mets.
My husband had normal ALP at diagnosis, but his mets were visceral with one very small blastic sacral bone met. Doc put him on Monthly Xgeva, Zytiga, Lupron, Prednisone. During the time he was on Xgeva, his ALP was below the reference range, in the teens. I could be wrong, but I attributed the low ALP to the decreased bone turnover caused by the Xgeva. Since Xgeva decreases osteoclast activity, the blasts don't have much to do! I couldn't find much on low ALP and Xgeva, esp in men, but I did find these two articles that indicate a relationship:
Your theory makes complete sense, Shanti. It's a wonder, though, that there is nothing in the official Xgeva "side effects" or some other academic paper with a note on this phenomenon.
Yes, I am perplexed by that as well. My theory certainly doesn't have enough evidence behind it to make any conclusions, but it seems like a possibility.
I shall heretofore refer to this as the Shanti Conjecture, with your permission of course. Based on all of my other personal information and data, this is still the most likely lead. But I will pursue a biopsy nonetheless, if only to rule out anything else.
I also had lytic Mets at diagnosis. All contained in my spine, but too many to count with the big daddy at T12. My PSA at diagnosis was only 11 (and 3.5 only 6 months before), so I also was perplexed and did a ton of research on the rarity of lytic Mets and possible neuroendocrine Pca, etc.
The MOs I talked to at the time said it’s not as rare as the internet claims, just that it’s not reported.
I did have my T12 directly biopsy. Not because it being lytic was a concern, but rather I had been hospitalized with pain and truly they didn’t know what kind of cancer yet. I never had a prostate biopsy because my PSA was 3.5 (to my belief at the time). So biopsy came back as Pca and it’s been a ride since.
Despite my lower range PSA (11 that day in the hospital) I do not seem to have neuroendocrine Pca. I did 10 rounds of chemo out of the gate. All visible Mets resolved. My PSA is still undetectable 2 years later. And my MRIs are still clean - although obviously not the most sensitive scan. But with PSA undetectable this is what insurance will approve for now.
Anyway, for me at least lytic lesions and low PSA were not an indicator of anything worse than usual. If anything, my results from chemo were well above average. Fingers crossed.
Thanks, BigM62...great story with a happy ending so far!.....this is exactly the type of information and history that I hoped to get from this post, and why this community is so important to all of us. We live on islands, but islands close enough to one another to communicate all of that important and relevant stuff that's otherwise "not reported."
The only way to beat fear and uncertainty is with information. Thanks for sharing.
Diagnosed 09/11/2019, PSA 1000+, with extensive pelvic, lymph nodes and vertebrae metastasis. Treatment, Lupron and Zytiga/Predisone, in 5 months PSA <0.02 and holding to date.
The lytic finding in my MRI was concerning, excerpt from result report:
"IMPRESSION: Extensive bony metastases as above. Although these can
represent prostate metastases by MRI, the lytic nature of these on CT
is atypical. As such, the differential diagnosis includes atypical
prostate metastases versus a second primary. Consider a bone biopsy
for further characterization."
So, did a biopsy from the largest vertebrae, T8, lesion coverage.
Biopsy impression:
"Immunohistochemical stains for pancytokeratin, CAM5.2, PSA, PSAP, racemase, and androgen receptor are negative."
So, no prostate cancer cells found.
At this point will inquire a bone specialist doctor, someone that can diagnose what's really there.
Orthopedic surgeons are tricky, most focus on the lucrative sports medicine track. Perhaps, a Rheumatologists, will look in the Boston area.
Funny, when posted a similar question here a while ago I got the same alarming advice to check for NE variant. I got all worked up and started harassing my doctors about it. I pissed off three independent MOs in different oncology clinics (two of them are excellence centers) so they ask me to calm the f@ck down (nicely).
Unless some retired oncologists and alike are lurking in here, we are all amateurs and don't know sh!t. Those in the field: researchers and clinicians do know, not all of it, but vastly more then we do. Plus each has set of own hindrances: field of interest, opinions, biases, blind spots etc. which doesn’t make understanding the big picture easier for everyone in the game.
The best is to take any advice from the Internet (including here) with a healthy grain of skepticism even if it sounds "authoritative". Do your own research and consult a qualified professional, and if you don’t like the answer, consult another one. It’s best to make informed decisions validated for your specific situation taking an account the entire context.
I found that having lytic mets is not an indication of NE disease. Typically, this form develops in the late stage and in PCa case after long continued advanced antiandrogen therapy. Inferring NE malignancy by the mere presence of osteolytic lesions in de-novo patient who hasn’t been on any androgen therapy yet is a non-scientific speculation.
I read that NE tumors are pretty rare (1-10 per 100,000) and even in NE cases bone lesions are predominantly osteoblastic and few are osteolytic. Lytic lesions development is not driven by tumor cells directly, it’s done by osteoclasts. Parathyroid hormone-related protein regulates plasma calcium and other critical cytokines that can kick osteoclasts into a lytic mode. It’s known that NE cells secrete pro-osteolytic factors and perhaps may nudge osteoclasts in the said cycle. But there’s no established causality link between having lytic lesion and inferring NE automatically. For patients like us, it’s most likely an individual’s genetics and other bio-physiological factors led to osteolytic events.
Did you do any genetic profiling for known mutations? I found a germline BRCA2 which explains early diagnosis. It’s known that most breast cancer metastases are osteolytic, can it be linked to BRCA mutation? Do you have any autoimmune conditions? I have ankylosing spondylitis since childhood. This led to systemic inflammation which as we know is a breeding ground for all kinds of cytokines as well as activation of pro-onco pathways. Plus, in my case this inflammation and a great deal of pain was in exactly the same spots where lytic lesions were detected later.
Nowadays, researchers are looking into tumor microenvironment and they see elevated levels of the same stuff I've been harboring there as a result of inflammation: TGF-b, interleukines (IL-11, IL-17 etc.), NF-kb, insulin-like growth factor etc. Anything from this list could switch osteoblastic process into osteolytic.
One of the interesting developments is how tumor microenvironment can provide clues for better targeted treatments. In our case research like this one can be beneficial:
Distinct tumor microenvironments of lytic and blastic bone metastases in prostate cancer patients
The authors of this research found that osteoblastic lesions had elevated pSTAT3 and JAK-STAT pathways while in lytic it was PI3K-AKT all jacked up. If this is not fascinating enough, in other literature PI3K/Akt has been implicated in regulating innate immune system so here goes another trace to check origins of autoimmunity.
Downregulation of miR-133a-3p promotes prostate cancer bone metastasis via activating PI3K/AKT signaling
Thanks for the complete reply, henukit. I did a lytic lesion search here before posting, but didn't find your original one...it would have helped - I hate reinventing the wheel. I am not overly fretting - no point to it - and your post in particular supports some of my standing theories - not hypothesis, mind, I didn't have any of this information.
As I discussed it with my wife, the continued unexpectedly low ALP simply means that I am operating in a slightly bigger data void than others with forms of APCa that may track with ALP levels. At the end of the day, I strongly believe that how I feel along with blood work showing the traditional markers associated with homeostasis (e.g., CBC, and liver workup) is always more important in any instant than my personal hobby of coming up with theories in my PCa biochemistry research.
With NE incredibly unlikely given my history, I was more interested in the possibility of having a history like that of Dark Energy (see above). Odd.
What started this was a question of why my ALP was normal. I still don't know why, but these post responses are a great point of consideration. I do lean heavily towards your argument that my etiology...our etiology... is rare enough to be some sort of subcategory of its own; as you say " For patients like us, it’s most likely an individual’s genetics and other bio-physiological factors led to osteolytic events."
Unfortunately, I have not pinpointed the genetics yet - and I say "yet" because there is a lot of family history. The BRCA mutations came up negative for me (when done in 2016), although both my mother and aunt (and an unknown number of other female relations) had early onset breast cancer in their mid-to-late 40s...just like me and my PCa.
Sorry to hear about your AS - you and your peers are my heroes; my favorite professor in undergrad engineering had AS and put all of us young people to shame moving about when we worked in the field. He was the first one that really taught me that we live through intent and not simply what we are given. His example was one I've drawn on repeatedly through this journey.
I do not have any diagnosed AI diseases, but again, there is some family history - my mother has Graves' hyperthyroidism.
Yes, the complexity behind our individual conditions is amazing...I've already started into the articles you've recommended. Thanks for the material!
I don't think I posted a dedicated post on lytic mets, it's somewhere in my other posts. I had three lesions that were completely resolved after chemo and radiation. I just finished the second chemo, a double blow one: cabazitaxel + carboplatin. I will do scans in a couple of weeks.
AS is a b!tch but you learn to live with it. Over the past 10 years was able to get it into a pretty stable remission using diet and healthy lifestyle. Still had occasional flares and pain. I'm grateful that still able to stand straight and can do most of the activities, I'm just not your youga man anymore Unfortunately, it was AS that played a major role in missing the onset of prostate cancer. At some point I started having strong back pains again with additional discomfort in the colon area. Since the spine pain was localized in the same old area and I didn't have any other PC specific symptoms I was never screened for PSA (too young according to guidelines). I also was doing regular blood tests (CBC, CMP, CSR) as a part of regular follow up with rheumatologist and nothing was alarming in those. I believe my ALP was always in the 70-90 range while elvated CRP and ESR are typical for AS. By the time we ruled out AS and everything else in that famous flare and did the PSA it was already 500. That's the extent of human ignorance.
Ignorance? Nah, it was your basic human hope that the universe wouldn't pile on more stuff, especially since you accepted and were working through AS. As I always told my children on the way out the door to school: "Be careful, the universe is trying to kill you.."...my daughter is in college now and she still finds that valuable.
Too bad I ignored my own advice. Yah...that part about "too young"....for a year before I found out I had what I called my "prostate pee" thinking it was BPH... I got the diagnosis for my 49th. Ignorance, indeed.
Funny, you mentioned "universe", that's what my wife likes to refer to. We just had a short vacation where she suffered serious injuries and is recovering from the surgery with a lot of pain. And I had to leave her in the hospital in another state, fly hometown to get my chemo, and then come back to bring her home. So, she is like "What the f#ck the Universe is trying to tell us, honey?". I just mumbled something about entropy.
So hey, I got DXed at 48, so we are two young ignorant bastards, yeah? And we are gonna beat the sh!t out of this s.o.b., mate!
Wow. An epic adventure of survival, indeed, henukit! You are a survival machine. And I absolutely love the "entropy" answer...I'm gonna start using working into more of my conversation...it sounds like something I'd say anyway - I love thermodynamics in school. Q: "How's it going?" A: "Well, you know, same old same old. Entropy and stuff. "
I hope your wife is home and on the mend!
BTW - What was your trigger point to start up cabazitaxel + carboplatin? Increase in PSA or....?
Thanks, she is home and recovering. Not a fun injuries (ribs and pelvis), lots of pain but luckily all mend able.
Few things:
1) Spike of CEA and PSA shortly after the first chemo and overall aggresiveness of the disease
2) BRCA2 positive and it's known that those who have it respond very well to carboplatin which is given to PCa patients in combo with cabazitaxel.
3) Extend survival by putting max pressure on the s.o.b.
And btw, thanks for that moniker "survival machine", I loved that too. I may use it as a title for guitar album (which I'm planning to record) or perhaps a book about crossing North Pacific I did just before the diagnosis.
North Pacific, eh? If you are familiar with Alaska, a possible meaning of "henukit" springs to mind. There is also the indication of the likely extreme sport nature of the henukit family. As an EMT for 20 years, I know all too well that it takes a lot of energy to injure the pelvis. I wish her speedy and full recovery!
Was CEA testing always a part of your regimen, or a decision based on the BRCA2+? I am a year into Zytiga and PSA is low, but there are indications of slow rise and I concur with putting max pressure on the beast. This means chemo again before going back to a biochemo like Xtandi.
You should indeed write that book, henukit. An amazing journey in any vessel! If you tell me it was in a kayak, I will...well, I dunno what I'd do. Hit the floor with my jaw, maybe....
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Who here is Worf, I wonder....? 
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