BCR but Neg PSMA scan, ? appropriate ... - Advanced Prostate...

Advanced Prostate Cancer

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BCR but Neg PSMA scan, ? appropriate next step

FlyJ profile image

Review of my clinical Hx: 68 y.o. good health. Pre-op PSA 31. Robotic RP and pelvic lymph node dissection 7/2019 (only two lymph nodes removed). Gleason 9 (4+5) Mixed acinar with extensive ductal features. T3a N0MO with 2 ECE no SV involvement. Margins negative. Color genetic testing + for NBN gene mutation only. Decipher score .82 (high risk)

Post Op PSA

9/19/19 <.1ng/ml

12/10/19 <.1ng/ml

3/16/20 .1ng/ml

6/15/20 <.1ng/ml

9/21/20 .1ng/ml

12/8/20 .1ng/ml

4/14/21 .1ng/mi

12/3/21 .21ng/ml

2/2/22 .21ng/ml

3/28/22 .18ng/ml

5/18/22 .15ng/ml

By definition BCR 2/2/22. PSMA Gallium PET ordered. Insurance denial and after appeal/time approved and done 5/18/22. PET scan without ANY areas of abnormal uptake. I had anticipated need for salvage radiation with ADT. However, my last two PSA values are falling....... I am following healthy diet, reached BMI of 22, exercising, taking a number of "repurposed" medications and "complementary supplements". I will be seeing radiation oncologist for primary consultation in one week.

Looking for advise/input from this group prior to consultation. I appreciate the deep knowledge/experience of the members.

45 Replies

It is wishful thinking that your PSA is falling due to variations in the second decimal place. Your repurposed and complementary supplements may be interfering with the PSA test.

You don't need a PSMA PET scan, you need whole pelvic salvage radiation.

FlyJ profile image
FlyJ in reply to Tall_Allen

Thanks T.A. I am familiar with 3-Year Freedom from Progression After 68Ga-PSMAPET/CT–Triaged Management in Men with Biochemical

Recurrence After Radical Prostatectomy article and Results of

a Prospective Multicenter Trial and the NRG Oncology/RTOG 0534 SPPORT trial. It does seem like early Salvage Radiation/ADT is helpful in BCR with even with Negative PSMA Pet scans especially with low PSAs. Addition of pelvic nodal radiation to the pelvic bed radiation reports better outcome in a the five years reported especially in higher risk pts. (At a cost of higher SE) My decrease in PSA may "not be significant" but certainly shouldn't portend rapid progression either.

Tall_Allen profile image
Tall_Allen in reply to FlyJ

Many patients rely on PSMA PET to detect recurrence. It's good, but not that good - especially not at low PSA. You have to treat what you can't see, as SPPORT showed.

FlyJ profile image
FlyJ in reply to Tall_Allen

It would seem that way. I did see Dr. Eugene Kwon in his presentation on recurrence say DON'T treat unless you have a target (i.e. don't do radiation blindly) . Later he seems to be concerned about "in field failures" which might be more likely with "carpet bombing PET negative areas". He may be in a minority opinion in that approach from what I understand.

Tall_Allen profile image
Tall_Allen in reply to FlyJ

Yes, he is infamous for expressing opinions without evidence. He is not an RO, or even an oncologist - just a genomics researcher who likes to express his opinions on videos to patient groups, but not to peers.

Tumors smaller than 5 mm are invisible on even the most sensitive PET scans. SPPORT showed that salvage whole pelvic RT+short-term ADT could cure patients who are recurrent:

thelancet.com/journals/lanc...

Incidentally, this approach is also standard of care in high risk patients. Waiting until you can see metastases is a self-fulfilling prophecy.

prostatecancer.news/2021/06...

FlyJ profile image
FlyJ in reply to Tall_Allen

Thanks T.A. Can I get your opinion on the following article: Nasser, N.J. Androgen Flare

after LHRH Initiation Is the Side

Effect That Makes Most of the

Beneficial Effect When It Coincides

with Radiation Therapy for Prostate

Cancer. Cancers 2022, 14, 1959.

doi.org/10.3390/

cancers14081959

Seems to make biological sense.

Tall_Allen profile image
Tall_Allen in reply to FlyJ

Thanks. It is true that radiation kills rapidly replicating cells most effectively. Also see this:

prostatecancer.news/2016/08...

I don't know how true their hypothesis is. Androgen deprivation alone using an LHRH antagonist (which has no testosterone surge) when combined with radiation is as effective as an LHRH agonist.

sciencedirect.com/science/a...

Casodex is often used to block the surge

Nusch profile image
Nusch in reply to Tall_Allen

Dear TA, agree with everything you say, just a comment based on my personal experience:m. The statement in your second link „We know that the time to be able to see the first few cancerous pelvic lymph nodes is often several years, so 2.5 years of follow-up tells us little. The newly approved PSMA PET scans will be able to rule out the larger metastases (>5 mm), but will never be able to find metastases smaller than that.“ as at least not true for me. In my PSMA PET in 01/2022 we found three PLN mets, all with a size of 2-3 mm. As assumed none of these showed up on the CT scan with we did for planning purpose on start of CBCT/VMAT radiation.

Tall_Allen profile image
Tall_Allen in reply to Nusch

PET is always done with a CT. They look for a CT correlate to the PET scan - CTs are unreliable below 5 mm. Unless the metastasis is highly PSMA-avid, there will be no CT correlate. Otherwise, it may be a false negative.

Nusch profile image
Nusch in reply to Tall_Allen

SUV max was 12.

Tall_Allen profile image
Tall_Allen in reply to Nusch

That's avid enough, but many patients with small lymph nodes have equivocal or no avidity. The sensitivity of PSMA/CT for finding cancer is only about 50%.

FlyJ profile image
FlyJ in reply to Tall_Allen

My PET/CT 5/18/22 results:

FINDINGS:

Overall PET and CT image quality and inter-modality registration are

satisfactory.

Mediastinal blood pool SUVavg: 0.9

Hepatic parenchyma SUVavg: 2.9

Physiological radiotracer uptake in salivary glands, lacrimal glands,

liver, spleen, duodenum, proximal small bowel, kidneys, and urinary

activity.

A. Prostate bed:

PSMA-RADS: 1A. Status post prostatectomy. No abnormal PSMA radiotracer

uptake is noted in the prostate bed.

B. Pelvic lymph nodes (N+ disease):

PSMA-RADS: 1A. Within pelvic lymph nodes, the PSMA radiotracer uptake is

within normal range.

C. Soft tissue involvement (M+ disease):

PSMA-RADS: 1A. Within the soft tissue, the PSMA radiotracer uptake is

within normal range.

D. Bone involvement (M+ disease):

PSMA-RADS: 1A. The osseous PSMA radiotracer uptake is physiologic and

unremarkable.

E. Incidental findings:

No other significant (anatomic) findings are noted in the head, neck,

thorax, abdomen, pelvis, and proximal lower extremities.

INTERPRETATION:

1. No abnormal PSMA expression to suggest presence of prostate cancer.

Note that a small percentage of prostate cancers do not express the

FOHL1/GCP-II enzymes targeted by PSMA tracers.

What are the supplements, and re-purposed drugs you are taking? Also, how do they[Biopsy] exactly describe the Ductal portion of your Pca? If most of your Pca is Ductal Type--then PSA will not be a great way to monitor your disease. It could be an indicator--but scans are best as well as making an assumption that whatever is left is in the Pelvic Region--and as someone else said Salvage Radiation might be best. And then again Ductal Cancers sometimes react well to radiation, and sometimes they do not. Depends on the population of Stem Cells, which no one can tell at this time.

Nalakrats

FlyJ profile image
FlyJ in reply to Nalakrats

My path report on Histologic type: Mixed acinar and ductal with extensive ductal features- U. of Mi. path department. My current "repurposed medications" Metformin, atorvastatin, loratadine, celecoxib, vitamin D, and melatonin primarily. I believe a variety of "whole plant based foods" are the best supplements. I do take a number of oral supplements which I have switched to nano or liposomal versions for better absorption and bioavailability. I try to include those that affect multiple pathways and still cycle these to prevent adaptation.

I understand that in vitro (cellular) and in vivo (mouse) studies are not directly applicable to us. I also understand that we will probably never see phase 3 studies using generic medications and certainly not non-patentable supplements. I do believe that synergy with different treatments types/medications/supplements are most likely very important to producing lasting results- this makes research/trials very difficult to do. Current SOC: one step- fail, next step- fail, and so on has had some good success but has not been curative. This does seem to be changing now but it will be too slow for many of us.

Nalakrats profile image
Nalakrats in reply to FlyJ

Good Basic List you have--I favor Liposomals and Super Critical CO2 Extracts, myself.Were the 2 lymph Nodes Clean or Dirty?

Nal

FlyJ profile image
FlyJ in reply to Nalakrats

Lymph nodes. One on left and one on right pelvis removed and both negative

At a PSA value that low it is unlikely that a PSMA PET/CT detects anything. This chart shows the probabilities that you will detect mets.

Fendler 2019
Positive22 profile image
Positive22 in reply to GP24

Interesting chart. Thanks for sharing.

Justfor_ profile image
Justfor_ in reply to Positive22

Yes, it is interesting as it explains the low success rate of sRT, which is roughly 35-65%. Those that have distant metastases, or a mix of local + distant, will only get the late toxicities out of sRT. Failure is guarantied. Your negative PSMA places you in a better league. Hope that you understand this because most people fail to do.

healthunlocked.com/prostate...

FlyJ profile image
FlyJ in reply to Justfor_

Thanks. Yes no guarantees of success in this journey. But no Rx at this point does guarantee progression of disease.

Justfor_ profile image
Justfor_ in reply to FlyJ

A very common mistake, that I have repeatedly tried to rectify, is that they correlate PSMA detection rate ONLY to the pre-test PSA value. PSADT, a more significant parameter, is systematically overlooked.

"The positivity rate of 68Gallium-PSMA-11 ligand PET/CT depends

on the serum PSA-value in patients with biochemical recurrence

of prostate cancer" (2019)

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6817454/pdf/oncotarget-10-6124.pdf

According to the "classic" definition you are NOT BCR. It requires 2 to 3 ascending PSAs above 0.2. You have two stagnant 0.21.

Now lets get more serious:

1) The negative PSMA is great news. Means that whatever is there is in low concentration, bellow the detection threshold of the PSMA imaging. A corollary to this is that it is easier to kill.

2) It is also known that there is a bumpy region in the PSA trajectory. Mine was between 0.1 and 0.15. Others have witnessed it around 0.15. Yours seems higher. From my own experience I can tell that, eventually, it will resume its ascent in the future.

3) Comparing the time you had your RP with mine (23 May 2019) my best guess is that your PSADT is somewhere around 9-10 months. It is the gray range in terms of aggressiveness.

Taking all those into consideration, I would continued monitoring PSA on a monthly basis until a clear BCR indication gets registered.

PSA
FlyJ profile image
FlyJ in reply to Justfor_

When I use the Sloan Kettering nomogram for PSADT, I get a wide range of results depending on what PSA dates I pick but generally in the 19- 23 month range.

FlyJ profile image
FlyJ in reply to Justfor_

Thanks for sharing your chart Justfor_. I have not heard of men who have had a relatively steady or rising PSA then have several decreases. I am wondering if anyone else on this site has had or heard of similar experience.

Justfor_ profile image
Justfor_ in reply to FlyJ

I don't think you will find anyone, because your question is not depicting what I pointed out. Decline after "steady or rising PSA" is not what YOU and I have witnessed.

Rapid succession and consequent correction is what I actually brought about.

I for one, had a jump from 0.08 to 0.15 in a very short time. My PSADT up to 0.08 was 9 month-ish and then plummeted to 5 months or so. Yours, went from 0.1 to 0.21 in ~7.5 months*. So, at least in my case, after the fast PSA speed-up a slow-down followed to bring things back to normal rates. Check how my latest 6 samples align with the first 12 or so. At that point there was conclusive evidence I was recurrent and started the Bicalutamide maneuvers.

(*)If you had a better time series I could had run your numbers. With what you posted there is no meaning doing that.

I would start Lupron and plan on salvage radiation. Chances are there is a LN involvement, but PSA is too low to pickup on PSMA scan. If PSA drops to zero on Lupron, it means there is hormone-sensitive PCa there, and secondly, Lupron would sensitize the PCa to radiation. I would also test for CR-P to get an indication of possible NEPC, which doesn't emit much PSA.

FlyJ profile image
FlyJ in reply to timotur

Thanks timotur. Is NEPC seen this early even before any ADT Rx?

timotur profile image
timotur in reply to FlyJ

Usually not (1%), but what is concerning is ductal + G9.... I would baseline CR-P now and look for a trend. One of our former members, Tom67inMA, developed NEPC rather quickly with very low PSA. Ductal and NEPC are characterized by some of the same markers.

"Using a well controlled, single-cell RNA-sequencing (RNA-seq) data set23 generated from mouse CTCs and their matched GFP-labeled parental tumor cells, we assessed neuroendocrine gene expression utilizing a gene signature distinguishing neuroendocrine prostate cancer (NEPC) from prostate adenocarcinoma (PCA) (hereafter referred to as NEPC gene signature)11. We detected a > 2-fold enrichment in NEPC up genes vs. PCA up genes in 66% (12 out of 18) of the CTCs analyzed compared to 20% (5 out of 20) of single-cell counterparts from the parental tumor (Fig. 1g). Taken together, these data suggest that the presence of tumors cells with neuroendocrine differentiation features is correlated with poorer survival and a shortened time to recurrence in PDA, consistent with the presence of neuroendocrine markers and expressed genes in CTCs and the idea that ductal-neuroendocrine lineage plasticity may contribute to aggressive disease."

nature.com/articles/s41467-...

FlyJ profile image
FlyJ in reply to timotur

is this CR-P the C reactive Protein blood test?

timotur profile image
timotur in reply to FlyJ

Yes, CRP should be < 1.0, others are Serum LDH, CEA and Chromogranin A.

healthunlocked.com/advanced....

Anomalous profile image
Anomalous in reply to FlyJ

There are a number of tests you can take that would tend to show that; or eliminate that from consideration.

FlyJ profile image
FlyJ in reply to Anomalous

Google comes up with : Neuroendocrine proteins including CgA, S-100B protein, synaptophysin, GFAP protein, and neurofilaments, typically located in neural tissues, are commonly used as markers for neuroendocrine carcinomas. Does that sound right? Are there "standard ones" ordered to evaluate prostate cancer for neuroendocrine transformation?

Anomalous profile image
Anomalous in reply to FlyJ

Having similar fears as yours, I came up with this list: fibrinogen, c-reactive protein, full hepatic function panel, LDH, alkaline phosphatase (bone specific) sed rate, Chromogranin-A. Its hard to get doctors to ask for all these tests. Cost me $533 at Ultalabs. I think CT scans and regular imaging also are helpful.

FlyJ profile image
FlyJ in reply to Anomalous

Thanks for letting me know your path.

I have been where you are. After RP, was >0.01 for one year, then started HRP (history of low T that affects life) with approval of URO. 6 months later 0.10, then .16, .19, .21, .36. As my PSA rising, I did talk to RO and URO who suggested SRT. Was during covid and needed an infected hip replacement replaced before anything else. As PSA was rising, I started on alternative treatments including Tippens and Artimisian, and others. PSA dropped to .29 over next 6 months. You are correct. You never see PSA drop on its own so I was hopeful of avoiding radiation. Since I knew RO sees things as radiation needed, I did a second opinion with a MO at Northwestern (Dr Morgans-now at Vanderbilt). Told her everything and her response was very straight forward. She basically said, yes your alternative activity is working now, but cancer is smart (as we all know) and will eventually figure out a way around it. She didnt understand why I wouldnt go for the kill shot now when burden low, especially since SRT has very few side effects. Again, I was not going to be treated at Northwestern if I chose SRT so she really had no skin in the game and I felt was just being honest. I did the SRT at U Chicago, without ADT. Both she and my RO said it does not give much better results when SRT started when below 0.50. PSA right after SRT was 0.15, then 0.06 at 6 months out, 0.02 9 months out and will be doing 1 year next month. I still take MCP, Pom juice, etc, etc, and pulse those 5 months on, 1 month off, eat 90% plant based, have always exercised and lifted. If I were you, I would test PSA every 3 months and as soon as the fall reverses, if it ever does, I would do SRT. Have no side effects 9 months out. Good luck brother.

FlyJ profile image
FlyJ in reply to Teufelshunde

Yes our paths seem to be similar brother. I took the Curt Michael Graydon protocol version of artmenisinin and fenbendazole prior to each drop in my PSA. Used them back to back (3 wks each) then PSA dropped from .21 to .18. Next used them concurrently and PSA dropped from .18 to .15. So very soon must make the decision on eSRT your "kill shot" or perhaps see if I can make more progress with complementary Rx before starting SRT

Teufelshunde profile image
Teufelshunde in reply to FlyJ

I did them separately and I had a doubt about one of the artemisinin products that I used since it had no effect. I see no need to rush in SRT. Remember that the ultimate upper limit for action is 0.50. The SRT results over that go downhill fast. My PSAs were around the 0.30 mark (.36, .30, .32, .30, .30, .32, .29). I tested every month. If you are more around the 0.20 mark you have a little more leeway. I guess I just got tired of testing and worry after a while. We will see if the "kill shot" worked. Looks pretty good now at 0.02 (again, no ADT) but we will see. You should also look at sulforaphane, MCP, licopene, and Nalakrats stuff on senolytics between your kill cycles. Here is the study on sulforaphane. I take the exact product (BROQ) and dose they used.

pubmed.ncbi.nlm.nih.gov/259...

Did they happen to do a Decipher Score? All the information I've read is that Very Early Salvage Radiation is nearly as effective as adjuvant radiation and the cure rate is higher the earlier you start, so I would not wait around...especially since you did have some Gleason 5 and that does not always give you the higher PSA's.

FlyJ profile image
FlyJ in reply to RJAMSG

Decipher score .82 (high risk) I had that checked because it was needed to help with the decision about whether to add ADT to SRT starting with low psa.

Blackpatch profile image
Blackpatch in reply to FlyJ

What about the PORTOS reading in your GRID? I was Decipher 0.91 but extremely good PORTOS, and went for eSRT at PSA of 0.12 plus 8 months zytiga and 12 months ADT - T recovery started about 7 months post ADT and was complete a few months later. I have now been undetectable for ca. 22 months post-full T recovery, and am pretty happy with the outcome, particularly as I had bilateral SV invasion. The high PORTOS was what tipped me over the edge of doing the very early SRT and high intensity ADT.

I corresponded with Spratt and others in the US and they confirmed the local view, that the high Decipher meant go early and go hard on the eSRT/ADT. It has taken while to get back to the "old me", but I think the addition of ADT is critical - and you can make it easier by remaining active, which I did not.

FlyJ profile image
FlyJ in reply to Blackpatch

I was not aware of the PORTOS gene signature until reading your post- thank you. I checked the site : prostatecancerinfolink.net/... They say they offer it to everyone who had a decipher score (which I did) but have not heard about it. Looks like U. of Mi. participated in this study, which is where my surgery and decipher score was done. Will ask my R.O. about it when we meet this week.

Blackpatch profile image
Blackpatch in reply to FlyJ

if you had Decipher run on a prostate pathology specimen (as opposed to a pre-RP biopsy specimen), you get the full GRID print out that includes PORTOS and a number of other gene signature information. It's hard to interpret it all and it's provided on a "don't use this to determine therapy" basis, but that could alter as further large sets of patient biopsies are investigated.

The only gene signatures that stood out for me were two related to high rates of replication - and since radiation is particularly effective where there is fast turnover, I assume that's why my PORTOS was high, but I can't be sure. There's a further paper on PORTOS due out in the next year or so, I believe.

The literature shows that for PSA <0.5 there is not much of payoff for including hormones, check Daniel Spratt's infomration on that.

Well you have done the good research and have a good plan whole pelvic SRT. Question about adjuvant ADT remains. What I recall is that when stratified (subgrouped) by PSA levels, those with low PSA (<0.5) like yourself may not need more than six months ADT. But you can decide as you go along whether to stop or continue depending on your tolerance of it.

I would just like to point out this one interesting view and evidence that having an “androgen flare” right at the time of starting the SRT might be of maximum benefit. That would mean starting a LHRH agonist such as Lupron at the same time and NOT using bicalutamide with it. You are not at risk for adverse effects from the brief androgen surge anyway (no Mets and low PSA).

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

BTW: your combination of anti-inflammatory and genome protecting supplements can decrease PSA and prolong PSADT. So I am not surprised to see your PSA fall back some. I treated myself with a very similar regimen (except with curcumin and quercetin added), and my PSADT increased from 3 months to 18 months with no ADT added. Still using those as part of my regimen, which has since expanded.

Good to have you here FlyJ.

FlyJ profile image
FlyJ in reply to MateoBeach

Great to have company of fine men like yourself as we support each other. I appreciate your experience with the conditions of my situation. I do "read" the literature as questioning the use of ADT with very low PSA's and eSRT. Looks like my G9 and high decipher score may favor ADT for 4-6 mos. as a wingman to SRT. Interesting you have read about the use of the testosterone flare with a LHRH agonist at start of SRT making the radiation more effective. T.A. discussed this with me and I sent the article: Androgen Flare after LHRH Initiation Is the Side Effect That Makes Most of the Beneficial Effect When It Coincides with Radiation Therapy for Prostate Cancer to the R.O. who I will be seeing this Friday.

Happy to see you had a significant apparent benefit with the supplements you are taking. My lingering internal question is whether to delay eSRT as long as my PSA is decreasing. I don't want to lose the advantages of eSRT with a very low PSA level. Close monitoring of my PSA should mitigate the risks.

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