Why would a metastasis “disappear”

[lokibear0803]

I’m wondering why one of my rather small mets, near right seminal vesicle (RSV), could be detected in three consecutive PSMA scans over the course of almost four years, but then would seem to have gone away six months after stopping my most recent on-cycle of lupron.

Here’s the chronological sequence:

———————————————————————-

January 2018: PSMA PET calls out a “small focus of uptake within the right seminal vesicle, suspicious for recurrent disease”

October 2018: whole-pelvic EBRT is done. The January scan was used as a “general” guide for targeting, though like I say, it was whole pelvic.

December 2018-August 2021: ADT vacation, until PSA rises to about 7.5

August 2021: 18F-DCFPyL scan calls out “Interval increased focus of PyL uptake in a 7mm soft tissue nodule in the right seminal vesicle”

August 2021-February 2022: on-cycle of lupron + zytiga. In February, I received a 1-month lupron, and T has gradually recovered since then to a normal level by late May 2022.

January 2022: Ga-68 PSMA scan calls out “Focus of increased activity posterior to the bladder and just lateral to the right seminal vesicle, SUVmax 3.3, which is significantly decreased since the prior examination.” So, by this point the ADT has done what we expected, i.e. the RSV met shrank in size.

February 2022-present: ADT vacation. By now, the PSA has risen to 1.94, which has been a surprisingly sharp uptick — it rose from 0.05 in early May, after staying around 0.05 for March and April PSA levels.

July 2022: Ga-68 PSMA scan calls out “The tiny focus of uptake described lateral to right seminal vesicle on the prior exam is no longer present”. The scan report indicated no other metastates via PSMA uptake.

———————————————————————-

In short I am PSMA-negative.

However, given the approximately 4-week PSADT currently underway, that is not what I’d expected.

Nor would I have thought that the RSV met would have gone from detectable in January 2022 at SUV 3.3 (still on ADT at that point) to “no longer present” (no ADT since February, and testosterone is back to normal).

It is my hope that this indicates “mitotic catastrophe” from the October 2018 EBRT.

I’m sure there are dozens of other possible causes, including PSMA-negative disease. It’s not clear to me just when we’d expect PSMA-negative disease to emerge — ??

I welcome anyone’s speculations here. I’d say that buzzkill is not allowed, but my buzz is pretty much dead by now anyway.

Many thanks in advance.

[Tall_Allen]

The current PSMA PET scans are urinarily excreted, which means there are lots of false positives in exactly the place you mentioned. The low SUVmax reinforces that. I'd be suspicious of anything below 10 in that area.

[LearnAll]

Physiological uptake of Ga68 is in kidneys, ureters, bladder and salivary glands. Besides those sites which light up bright orange...some orangish hue may be noted in colon and rectal area. It needs a very skilled nuclear medicine doctor to read these scan accurately and not suspects mets where there is physiological, normal uptake of Ga68.90% men have PSMA positive mets and only less than 10% men have PSMA negative disease. Also, PET-CT used in Ga68 scan, PSMA negative disease can be seem as the CT part needs to be read and not just the Ga68 uptake part. SuvMax of below 9 or 10 are likely to be false positive.

[lokibear0803]

Tall_Allen and LearnAll — thank you for your replies.

I believe you are both suggesting that the RSV met did not so much disappear, as it was never really there to begin with.

So we’re ruling out mitotic catastrophe — agreed?

If so, do you have thoughts around why the PSA would be rising so quickly? I can come up with these possibilities:

-- prostatitis (would PSA continue to rise with this? or would it plateau?)

-- normal PSA from what's left of healthy prostate (mine was 0.5 nadir after 2006 EBRT)

-- radiation bounce involving micro-mets, i.e. not visible on PSMA PET

-- PSA too low for effective Ga-68 (PSA was around 1.8 at time of scan)

-- micro-mets that make a lot of PSA, very quickly

-- misinterpretation of scan from radiologist (i.e. some PSMA-positive cancer was missed)

-- PSMA negative disease (e.g. discordant FDG-positive)

If the explanation is micro-mets that quickly make a lot of PSA, I have to wonder “why now?” — I was on ADT vacation for almost 3 years without this kind of thing — i.e. PSADT was around 5.5 months when I restarted a lupron/zytiga on-cycle for 7 months. Could such an on-cycle trigger this kind of change in behavior?

LearnAll — I believe you’re saying that PSMA-negative cancer is found in only one out of 10 men with PC, but that if I have this, then we’d see it on the CT portion — am I understanding correctly? Is it possible there are PSMA-negative lesions that are below minimum size for CT to detect this?

Is PSMA-negative disease found primarily in castrate resistant PC, or even in mHSPC? Would we think it unlikely in nmHSPC?

Thanks very much for continuing to indulge my questions.

[addicted2cycling in reply to lokibear0803]

Why not have a PSMA PYLARIFY Scan ????

[lokibear0803 in reply to addicted2cycling]

Yes, in fact I have one scheduled. I’d assume you suggest this b/c F-18 is more sensitive at lower PSA values…but as it turns out, with a 4-week DT, by the time I get the F-18, my PSA will be high enough for Ga-68 to also be effective.

My radiologist has suggested getting Ga-68 since it’s the same one done in January, and this makes it easier to compare apples to apples.

But that still leaves the question of PSMA-negative disease. I’m looking into a 64Cu scan, and perhaps an FDG, to cover this piece of things.

[LearnAll in reply to lokibear0803]

If you are truly concerned with bone met growing your best bet is to closely monitor Bone resorption and bone formation bio markers.In Pca, if bone mets are growing..it will show increase in bone resorption and bone formation biomarkers. There are many biomarkers but I will tell you about 2 which are most important.

For Bone Formation (Osteoblastic activity) Bone Alkaline Phosphatase is most accurate and for Bone resorption(damage) Serum NTX should be used.

Because Bone mets cause bone damage and therefore body respond with emergency bone repair to keep bone from getting damaged...it releases Bone Alkaline Phosphatase which is an enzyme reflecting how fast the bone repair is going on (indirectly how much bone damage is happening)

Why Oncos do not recommend these biomarkers? Because Insurance companies deny it as these tests are expensive.

There is another way to know about PSMA negative bone mets and that is our good, old fashioned NM Bone scan (costs $150 -200 ) This is most sensitive scan so if there is lesion due to any cause..PSMA+, PSMA-, Scar tissue, Inflammation or old .injury...Everything will show .And you can focus on area which you suspect PSMA- met...and if nothing shows in Bone Scan at that place.. you Do Not have PSMA- met.

[lokibear0803 in reply to LearnAll]

Thanks, I’ll talk to MO about a repeat bone scan (last was 2017). However, I thought a PSMA scan already covers that base? Although, as you suggest, perhaps that’s only if bone mets are PSMA+.

MO says to do B-ALP when regular ALP is elevated, since they are correlated. My ALP has recently trended upward, though still within normal range. I’ll revisit this with her also.

In either event, I’m not necessarily concerned with bone met per se at this point — but it wouldn’t hurt to do bone scan and B-ALP.

Meanwhile, could I get you to comment on how likely PSMA- disease would be for someone in my situation — clinically BCR, mets never seen on conventional imaging, but with lymph node mets found via surgery and PSMA scans — technically nmHSPC? Is it still the 10% number you mentioned, or is it less likely for someone in earlier stage of progression?

Thanks!

[LearnAll in reply to lokibear0803]

If I was in your situation I will only do two tests (1) Multiparametric MRI to see primary tumor and (2) A Bone scan. If both are clear I won't worry.

[lokibear0803 in reply to LearnAll]

Thanks, LearnAll — I’d think you suggest mpMRI since it’s not dependent on PSMA uptake, right? Are there some other advantages of mpMRI over PET scan?

Is there some minimum recommended size of mets, and level of PSA, before mpMRI is effective?

[LearnAll in reply to lokibear0803]

multiparametric MRI of prostate does not depend on PSA or PSMa etc. This scan takes hundreds of slices (less than 1 mm each) of prostate gland and analyses each slice to see if there are any changes in the architecture of prostate cells..and if yes..then to what extent these cells are cancerous. This is done thru what is called "PIRADS System" If shape and type of cells fall into 2 or less, it is certainly Not Cancer. If pirades score comes 3 its "iffy" more likely non cancerous. If above 4or 5,it. is cancerous .Besides this scan can also diagnose BPH by the way prostate cells look. And to some extent it can also tell if prostatitis is there by finding out degree of inflammation.

But, the information obtained by mpMRI is limited to prostate gland pathology ONLY.

Any bone mets have to seen with Bone Scan and/or Ga68 PSMA scan. Any visceral mets can be located by MRI with and without contrast.

Let me repeat, PSA is not a factor in mpMRI as this scan just determines cancer cells by their morphology (shape,size etc).

[Justfor_ in reply to LearnAll]

LearnAll you wrote: "This scan takes hundreds of slices (less than 1 mm each)..."

Have you, or anybody else reading this, run across such a super-fine axial resolution? The two 3T mpMRIs I have had so far used a 3mm axial step, which I believe is an established value:

radiopaedia.org/articles/pr...

[LearnAll in reply to Justfor_]

A few months ago, I got mpMRI and asked the radiology tech while he was doing it. He said he will be taking 1 mm wide slices on this 3 Tesla machine. He may or may not be fully correct.

[Justfor_ in reply to LearnAll]

How long did it take for the full sequence? It took me about half an hour at 3mm slicing. Within this was the waiting time for the contrast to defuse around the body. So, let's subtract 15 minutes to also count in the initial placing on the table. This leads to about 15 min of net scanning time at 3 mm increments. If we now triple this for 1 mm increments and also add 15 min of idle time we get it to one hour.

[LearnAll in reply to Justfor_]

I do not remember exact time but it was like 45 to 50 minutes.

[lokibear0803 in reply to LearnAll]

Thanks! Great information —

[LearnAll]

lokibear, your list of things which causes increase in PSA should include BPH (Benign Prostatic Hypertrophy) In many PCa men, PCa and BPH coexist. So even if PCa is well under control, BPH cells keep releasing excessive PSA. BPH is treated with meds like Finasteride, Tamsulosin and Tadafinil (cialis). Sometimes, a combination of all three is needed if BPH is significant and causing LUTS like nocturia,frequency etc.

[j-o-h-n]

Radiologist finally cleaned that corner smudge off of his eyeglasses.....

Good Luck, Good Health and Good Humor.

j-o-h-n Sunday 07/10/2022 3:39 PM DST