If ADT can "hide" mets on PSMA PET CT, lesions can still be seen on MRI, no?

That's my question. How to know if mets are growing or maybe have disappeared on ADT (if this is really possible) or if on ADT + radiation ? PSMA CET CT best scan could not give a good result on ADT, what about MRI? Other options (would (bone) alkaline phosphatase still be a marker?)?

[LearnAll]

In pCA related bone mets, the type of bone activity which happens is called "osteoblastic" means bone is being destroyed but at the same time bone is being rebuilt.

Alkaline phosphatage is needed to rebuild bone. So, if alk phos is very high, it means bone is being rebuilt at a hgher rate....by logic..the bone is being destroyed at higher rate creating need to rebuild the bone....its the turnover in bone destruction and bone formation which determines level of alk phos enzyme.

[Tall_Allen]

ADT ± radiation shrinks mets if it can, so they may become undetectable on MRI or CT. ADT temporarily increases PSMA avidity, but decreases it over time. Bone ALP is a biomarker for actively growing blastic bone mets.

[Hidden in reply to Tall_Allen]

ok, but can ADT alone shrink mets?

[Advo__cate in reply to Hidden]

Yes, it did for my husband, also on zytiga.

[ctarleton in reply to Hidden]

I would say, Yes, ADT alone can shrink mets, in certain circumstances.

From my anecdotal personal experience starting from almost 6 years ago, I had very many bone mets and lymph node mets, visible on CT scan, NM Bone Scan, and standard MRI scan. Back then, I was on Lupron ADT alone (along with Zometa for bones) to start. At that time, PSA went from over 5,000 to 1.0. Appearance of quantity and extent of bone mets on "Christmas Tree" NM Bone Scan reduced by approximately 1/2 during the first year, due to standard ADT alone. Many lymph nodes reduced in linear dimensions by 50% or more, including one that was the size of a golf ball. ALP readings went from 400 something to the 70-80 range.

About 3 years ago I had Provenge and a Ga-68 PSMA PET scan and MRI as castrate resistance developed. The general appearance of reduced extent of bone/lymph disease had remained about the same; however, there were about 10 "hot spots" that did show up on the PSMA PET in several bones and lymph nodes. Subsequent Xtandi took PSA from 95.0 back down to 1.2. ALP went down further below 50. After 2 years 8 months on added Xtandi, PSA has slowly drifted back up to a little over 3.0.

Charles

[Tall_Allen in reply to Hidden]

Yes, of course

[Bjry in reply to Hidden]

I don't understand the meaning of "shrinking mets". Are they shrinking because some are killed? made dormant? some unknown damage to the tumour microenvironment?

[GP24]

If you start a Lu177 therapy, e.g. if you got into the VISION trial, you will be on lifelong ADT. They still will make a PSMA PET/CT to determine the extend of the disease and after two Lu177 cycles they will make another one to compare the two and see if the Lu177 worked. So the PSMA PET/CT is still sufficiently sensitive while on ADT.

The MRI will get the same results with and without ADT. But I do not think you will see more with an MRI than with a PSMA PET/CT while on ADT. Never heard of a trial that compared a PSMA PET/CT while on ADT with an MRI to answer that question.

[timotur]

If ALP decreases after a few months on ADT, is that an indication of bone Mets?

[Hidden in reply to timotur]

good question!

[timotur in reply to Hidden]

Well maybe not, it looks like ADT causes BSAP (bone-specific alk phos) to go up with mCRPC.

"In summary, serum levels of both BSAP and NTX are significantly increased by ADT in men with nonmetastatic prostate cancer. In contrast, BSAP but not NTX increases further in the presence of bone metastases. These findings have important implications in our understanding of bone metabolism, and may affect the manner in which bone-targeted therapy is studied and used in men with prostate cancer."

clincancerres.aacrjournals....

[EdBar in reply to timotur]

All of my docs including Meyers and Sartor have used Alka Phos as one of the key indicators for PCa activity. When I was dx it was 500, and PSA was 37. After ADT PSA dropped to undetectable, Alka Phos is in mid 50’s and scans show no active disease. This included a drop in BSAP.

Ed

[Fanger1 in reply to EdBar]

Hi Ed

My Alk Phos has ticked up to 89 after my PC was diagnosed. This is still wnl but before my diagnosis and unexplained back pain it was testing lower by 20 or more units.

[Shanti1 in reply to timotur]

This is because the loss of testosterone causes bone loss, but you should not see this if someone is given a bisphosphonate or xgiva while on ADT, which is hopefully true in most cases. My husbands alkphos was in the 20s on xgiva because of supressed bone turnover. If alkphos increases while somone is on ADT and bone medication, it is an indication to investigate for an active bone met.

[tango65]

In my personal experience, the treatment with Lu 177 PSMA made all the lymph nodes become PSMA negative, however the lymph node sizes remained the same. The radiologists considered that these nodes are not metastatic.

[Hidden in reply to tango65]

ok, but Lu 177 PSMA is equivalent to radiation and ADT not.

[tango65 in reply to Hidden]

Could you please post some references to data showing that ADT can "hide" metastases in PSMA PET/CTs?

My lymph node metastases were diagnosed with a Ga68 PSMA PET/CT. The PSA was 10. I started ADT immediately.

I got treatment in Germany 2 months later. My PSA was 0.6. The doctors in Munich ordered a Ga68 PSMA PET/CT before the Lu 177 PSMA treatment. The new Ga68 PSMA, showed exactly the same metastases as the initial scan. Same locations , sam SUVs even when ADT was able to reduce the PSA more than 90%.

[Hidden in reply to tango65]

The detection rate depends on PSA :

auajournals.org/doi/abs/10....

And you can have a PSMA-flare after ADT initiation or not, and this is being studied:

clinicaltrials.gov/ct2/show...

In your case, you started treatment after 2 months ADT, so, as Allen stated: "ADT temporarily increases PSMA avidity, but decreases it over time", in addition with PSA 0,6 you had 50%+ detection rate with PSMA PET CT according to the study above.

My was more a question than a statement: I wanted to know how to control progression on ADT and if ADT can really shrink metastasis, or just doesn't show on exams...

[Hidden in reply to tango65]

Here a case of almost undetectabel PSA and even non-PSA secreting PCA where PSMA PET CT still detects mets:

sci-hub.tw/https://link.spr...

[Fanger1 in reply to Hidden]

Thank you for posting this paper. I'm considering getting a Ga-PSMA Pet/CT scan and have a low PSA.

[cajeffrey in reply to tango65]

Your experience is very similar to my husbands. At diagnosis, Feb 2017 PSA 275, CT scan showed several enlarged lymph nodes, including the Para aorta lymph nodes.(no bone mets) He had radiation and started ADT, After four months on ADT his PSA was .08. In April 2018 he had an MRI to diagnose increasing lower back pain. The MRI showed the same lymph nodes which had "very slightly decreased in size". The same lymph nodes were enlarged in a non detectable PSA environment. Would like to get a Ga68 PET/CT but unfortunately this test is not available here in Canada. He is due for another PSA test.

[jedgar1]

After radiation failed I had a pet that shoed my lymph nodes had cancer and I had a met in my rib. 3T mri showed lymphs were clean

[Shanti1]

Hi Myriammole-

This thread brings up some great questions! Other PET (axumin, acetate) rely on prostate cancer metabolism to show a positive, so naturally, if ADT works, those will no longer show a lesion while the cancer is supressed. But PSMA is not metabolism related, it is a membrane recptor. I found a couple of studies that help to answer the question:

ncbi.nlm.nih.gov/pubmed/305... - This one shows that in the first 28 days after androgen blockade the PSMA can increase, but does so more in castrate resistant men.

ncbi.nlm.nih.gov/pmc/articl... - this one looked at long-term expression of PSMA in castration-sensitive men. Here are the results:

Results

Overall, 31 PC lesions were visible in all ten patients before initiation of ADT. However, during ongoing ADT (duration 42–369 days, median 230 days), only 14 lesions were visible in eight of the ten patients. The average tracer uptake values decreased in 71% and increased in 12.9% of the PC lesions. Of all lesions, 33.3% were still visible in six patients with a complete PSA response (≤0.1 ng/ml).

[MateoBeach in reply to Shanti1]

Yes, thank you Shanti1. This has important implications for those (like me) who are planning to have 68 Ga-PSMA PET scan and then possible 177 Lu-PSMA treatment.

It is favorable in both to have the maximum expression of PSMA: To "light up" the scan (formally measured as SUVmax); And then to present the maximum binding target for the Lu radioligand. The situation is different for castrate-sensitive and castrate resistant.

IN the castrate sensitive there is variable response: If bicalutamide is started, then PSMA expression (on scan) is increased in only about 38% but is decreased in 62%. So if one could have a baseline scan this could be tested on subsequent scan after a short term (21 to 28 days) course of bicalutamide, or possibly degarelix. Dr. Nat Lenzo of Australia Theranostics told me that he may employ this strategy for me with subsequent scans and treatment cycles. (His Ga-PSMA scans there are "only" about $900 US. I'm getting my baseline scan at UCLA.

For the castrate resistant, my reading is that long-term ADT (LHRHa) may suppress PSMA expression. But that short term it can enhance it. In the first cited paper all were enhanced with short term course of enzalutamide or abiraterone addition for up to 28 days.

[Shanti1]

These articles answer the question as to if ADT can kill prostate cancer. It can cause tumors to stop growing or even shrink as some of the cells die, but some cells in the tumor are likely already castrate resistant and can begin to grow. Other cells are not killed, just put in to a dormant state.

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

"it has been reported that prostate cancers contain both androgen dependent and independent tumor cells. The selective pressure of ADT causes clonal expansion of the androgen insensitive cells altering their relative frequency and leads to the development of castrate resistance"

journals.plos.org/plosone/a...

"Androgen deprivation therapy (ADT) commonly leads to incomplete cell death and the fate of persistent cells involves, in part, a senescent phenotype. Senescence is terminal growth arrest in response to cell stress"

ncbi.nlm.nih.gov/pubmed/240... - Early human prostate adenocarcinomas harbor androgen-independent cancer cells.

[jholmq]

I started Lupron and Zytiga in Jan of 2018. PSA at dx was 34, approximately 12 Mets to bones. PSA started rising and I had scans (bone and CT) and 9 Mets showed as healed, no activity. Had 3 remaining Mets with greatly reduced activity, all 3 were lytic, not plastic. Had a bone density scan and bones show as normal density. PSA is still rising and was 6.7 as of last Wednesday. I have scans set for tomorrow. My ALK has been solidly in the normal range throughout. The only thing different for me than many my age (64) is I was a gym rat, so started in better condition than most.