Radiographic Progression vs. Biochemi... - Advanced Prostate...

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Radiographic Progression vs. Biochemical Progression (Pluvicto)

noahware profile image
17 Replies

Some recent posts have talked about the possibility of seeing a "bounce" effect, of rising PSA or ALP, as a by-product of treatments such as radiation, BAT, Pluvicto, etc. Rather than indicating disease progression and ineffectiveness of treatment, such upward jumps in the numbers may indicate the death of cancer cells. Counter-intuitively, the bump up may be a sign of EFFECTIVE treatments. (I got such a bump in my ALP when I first began Zytiga: a sharp rise in ALP, to around 1000, a month after beginning Zytiga, was followed by sustained drops that leveled off in the 200s.)

I recently quoted Sam Denmeade saying of BAT that "when prostate cancer cells are exposed to T they are stimulated to make PSA, even if their growth is blocked by T. Thus, we cannot rely on PSA response alone to assess the effectiveness... BAT can [also] induce an initial flare response on the bone scan, as do many other effective prostate cancer therapies. Spots on the bone scan can appear darker, and sometimes new spots that weren't seen before can appear. Patients who appear to be benefiting [can] show an initial worse bone scan..."

So initial signals of progression, both biochemical and radiographic, may be deceiving. But is there anyway of knowing this until future scans, months down the road, actually confirm that progression is not occurring? My worry is, it seems like there is often going to be quite a lag time between the messages one gets (and tries to interpret) from blood work and the messages one later gets from scans, especially if the scans being used are not the most refined in picking up new mets (bone scan, CT).

To put this in the context of my own case, the series of CT and bone scans I have had over recent months reveal my disease to be "stable." Under the protocols being used to define "progression" within the Lu-177 arm of the Pluvicto trial I am in, my disease is not progressing. The lumbar CT I just had on Friday, due to some lower back pain, for example, said this: "Alignment is normal. Vertebral bodies and posterior elements are intact. Normal disc heights and endplates. No prevertebral soft tissue thickening. No significant change in multifocal predominantly sclerotic osseous metastases."

That last line seems to be the story of my treatment. But here is how the PSA and ALP numbers have progressed on Pluvicto (which I began on 4/5, and had a fifth infusion of on 10/21):

4/5, PSA 21

5/11, PSA 2.5 (Nice!)

6/2, PSA 14

7/29, PSA 33

9/6, PSA 40

10/21, PSA 50

ALP

4/5, ALP 355

6/2, ALP 243

7/29, ALP 335

9/6, ALP 298

10/21, ALP 644

I wasn't overly concerned about the rising PSA, because my stable (and even dropping!) ALP numbers seemed to confirm my disease maybe still could be relatively stable. I have yet to experience any significant bone pain that can be directly attributed to mets. But this last ALP number, from Friday, is truly alarming. Yet the PA I met with on Friday did not seem overly concerned by it, and implied that my MO would not be, either. (I have yet to speak with him but will obviously be addressing my worries.)

How would I not suppose this doubling of ALP might represent progression of bone mets that aren't yet being picked up on bone or CT scans? It seems almost impossible that this ALP number could reflect the "good news" that my Pluvicto treatments are a success. Yet by the trial definition of radiographically-determined progression, I am NOT progressing on Pluvicto!

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noahware
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17 Replies
cesanon profile image
cesanon

Well then how can you know if BAT is working or not?

Does anyone have an answer to this question?

If you can't tell if it is working in the first few cycles, BAT starts to become a dangerous treatment to try?

leebeth profile image
leebeth

No PSMA PET scan to monitor progression? Only CT and bone scans?

That is puzzling to me. My husband has PSMA scan and Guardant 360 test after every 2 cycles of Pluvicto. So baseline, prior to 3rd treatment, prior to 5th, and 6 weeks after 6th. This is protocol at his institution.

noahware profile image
noahware in reply toleebeth

I am assuming he is not in a clinical trial. Where is he receiving treatment?

leebeth profile image
leebeth in reply tonoahware

Correct, he is not in a clinical trial. That is standard protocol at Mayo, along with CBC with diff, CMP, and PSA prior to each treatment, and at home mid cycle at 3 weeks. He also has a bio distribution scan the day after each Pluvicto treatment to make sure it’s going to all the right spots. So he feels well scrutinized along his journey!

noahware profile image
noahware in reply toleebeth

A quick question regarding Mayo protocol: when first using a PSMA-PET to see if PSMA-directed therapy even makes sense for a patient to try, do they make additional efforts (like comparing to FDG scan) to see how much cancer will not be prone to cell-death via Pluvicto? In other words, prior to treatment initiation exactly what efforts are there to gauge relative likelihoods of how successful Pluvicto might might rather than just say "this has some chance of success?"

It is great that they are using PSMA-PET to help with real-time assessment of efficacy, but just wondering details about efforts at predicting degree of efficacy prior to beginning treatment. Clearly, Mayo seems to do more than just give a thumbs up to anyone who has PSMA-avid cancer. Thanks for any input!

[I am about to post a new thread with link to a lecture by Dr. G. Johnson of Mayo titled "PSMA Scans & Pluvicto (lutetium-177) in 2022" and my above question is related to something he says at 46:55 of the video.]

leebeth profile image
leebeth in reply tonoahware

My husband had a choline PET and the PSMA PET showed so much more activity that they were sure there was not discordance in the wrong direction. They would have happily ordered the FDG but felt it was not necessary

noahware profile image
noahware in reply toleebeth

Thanks!

MateoBeach profile image
MateoBeach in reply toleebeth

You are right to be puzzled by that: Not using regular PSMA scans to monitor progression in PSMA specific radioligand trial. Perhaps using older less-sensitive scans to bias results towards showing more progression free survivals.

leebeth profile image
leebeth in reply toMateoBeach

It truly makes no sense to me, if you want to actually know what’s going on! Skewing results is not a winning proposition long term.

noahware profile image
noahware in reply toMateoBeach

I didn't want to be the first to be so blunt, so thanks for doing it for me. It seems that ignoring possible signs of biochemical progression as well as foregoing the most-sensitive scans, in favor of a sole use of LESS-sensitive radiographic evidence, makes a lot of sense for those looking for preferred study outcomes.

EdBacon profile image
EdBacon

Thanks for sharing all the details of your treatment.

Have you had a PSMA PET scan recently? ALP has other sources such as the liver. I'd do the assay to see where the high ALP is coming from.

noahware profile image
noahware in reply toEdBacon

I am in a Pluvicto trial, and the only PSMA-PET done was the initial one to see if I could qualify. I do need to discuss the ALP with my MO, but other than becoming even slightly more "slightly anemic" my blood work looks pretty good. I am assuming the high ALP is largely from the mets, because my original spike in PSA (prior to Zytiga) was accompanied by a big spike in ALP. It just seems like the most likely cause.

EdBacon profile image
EdBacon in reply tonoahware

I also had a spike in ALP when I started Zytiga (PSA was coming down), but I think >600 is a bit beyond that. ALP can also go up if the bone is healing. My ALP was up there in the 600s at diagnosis and I had mets all over my skeleton and serious levels of pain.

I agree, the most likely source is the bone, but wouldn't hurt to verify. That's just my opinion though and what your doctor says is what matters.

noahware profile image
noahware in reply toEdBacon

Agreed. My ALP actually got as high as around 1300 before ADT and Zytiga (when I failed my attempt at ADT via high-dose estrogen), but never had any pain... I'd look at that number and think, gee, pain must be in the cards SOON. Symptom-wise, I've been extremely lucky given how some of my numbers and scans have looked.

noahware profile image
noahware

At this point, starting to wish I had sprung for the FDG scan right out of the gate! But the trial itself, along with my docs, have been relying on bone/CT scans alone, with no suggestion of either FDG scans OR additional PSMA scans.

noahware profile image
noahware

Thanks, good discusssion. (You gotta love how it begins with " Let’s assume cost isn’t an issue." Uh... let's assume that it IS.)

Purple-Bike profile image
Purple-Bike

If you are not certain, a test for bone specific ALP will give a better idea of possible metastatic activity, with liver activity not clouding the data.

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