Game changer in diagnosis?: ajmc.com... - Advanced Prostate...

Advanced Prostate Cancer

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Game changer in diagnosis?

Don_1213 profile image
14 Replies

ajmc.com/view/novel-assay-d...

Sounds like it.. a blood test that can find micro-cancer: "The test was able to differentiate between localized prostate cancer and metastatic prostate cancer, even detecting micro-metastases that advanced imaging would not detect."

More: eurekalert.org/news-release...

Hmmm... probably wouldn't even have to travel to LA for this. Exciting actually. No radioactive tracers, just a blood sample. It wouldn't provide targeting like PSMA-PET, but it would tell the patient if a PSMA-PET scan was called for.

I think it's something that could replace PSA as a diagnostic for PCa.

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Don_1213 profile image
Don_1213
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dockam profile image
dockam

Just saw that news also💙:

news-medical.net/news/20230...

Don_1213 profile image
Don_1213

The original paper: sciencedirect.com/science/a...

Cooolone profile image
Cooolone

Interesting... But we are aware the presence of CTC is more prominent with PCa that has spread. Would this test also fall victim to needing that transition in cellular aggressiveness to be present, therefore be useful, but only later in staging? I'll read it again a few times, just spitballing ;)

MateoBeach profile image
MateoBeach in reply to Cooolone

Agree Cooolone. I would not consider passing up definitive local and regional treatment if PSMA scan was negative and this scoring research tool was positive. And CTC counts and cfDNA liquid biopsy more established and can also provide genetic analysis.

Don_1213 profile image
Don_1213 in reply to Cooolone

I think you should read it again. This isn't looking for CTC's. From the writeup on the paper: "The assay analyzes extracellular vesicles (EV), which are microscopic particles released by cells throughout the body."

There is a fundamental difference between this test and a test looking for CTC's. This test looks for the particles "released by cells throughout the body" - ie - the entire body. All the cells. And it is able to recognize particles specific to PCa, and even specific to localized tumors or metastasized cancer.

I would think this would probably be a first use diagnostics tool - even before an MRI and certainly before a biopsy. Are there any cancerous cells anywhere in the body? If no - why continue looking? I'm fairly certain that this test will eventually be less expensive than an MRT, PSMA-PET scan and certainly less expensive than a biopsy.

That's why I said "Game changer" - it stands a good chance of modifying PCa diagnosis, and in a good way, avoiding unnecessary testing, and determining if more testing is needed.

Cooolone profile image
Cooolone in reply to Don_1213

PotAto - PotatO ...

Still the same effect, circulating blood substances... Released by tumors at a cellular level. Existing tests like this are great too, but not for everyone and typically once the disease has progressed. How would tissue within the prostate release into the blood cells? That characteristic is not associated with low volume or grade tissue. As I've said, the test itself then may very well lend to under-diagnosis or false negative(s). And any staining for genomic markers via blood is and has not been as accurate as tissue sampling. Just saying. Remember, it's not a blood borne disease, but tissue. At a cellular level...

Don't mind me, I'm a cynic, and always a doubter until I see proof. A sample size of 40 patients isn't enough for me. And I don't believe in Unicorns. The tests also misses plenty of markers that are not being tested for, so it's not as much a game changer (for me) in my mind. But the tract they're venturing down is definitely Interesting, not taking anything away from that. I believe the genomic side of things will eventually taylor into individualized treatment for patients some day, as opposed to today's convenient "group" risk stratification and therapy application.

But until then ;)

Don_1213 profile image
Don_1213 in reply to Cooolone

I think you REALLY should read both of the references above and THEN read the original paper. What they're analyzing is "extracellular vesicles" I'd suggest taking that to Dr. Google and read up on it. ALL cells in the body produce these. And they travel through the body in the blood (and all cells in the body pretty much depend on blood circulating to deliver oxygen to them - when that stops the cells die.) They can be found in the blood and in urine. They are specific to the type of cell that makes them including PCa cells.

Direct from Dr. Google: "Do all cells secrete extracellular vesicles?

They carry various components of the cytoplasm and cell membrane that are selectively loaded into these vesicles. They are secreted by all forms of living cells and play essential roles in different physiological functions and pathological processes." - "all forms of living cells" includes cells making up the prostate gland.

Can you clarify where you found "staining for genomic markers via blood" ? That isn't what's being done.

I doubt if the authors of the articles above would have published what they did if they didn't see the value of the research and the findings of the original paper's authors.

I'm not a cynic - there's no gain to that nor is it applicable to the scientific method. I am skeptical which to me is a more useful trait. In this case - the skeptical me says there appears to be real value for diagnostics in these findings.

Oxford dictionary:

Cynic: a person who believes that people are motivated purely by self-interest rather than acting for honorable or unselfish reasons. "some cynics thought that the controversy was all a publicity stunt"

Skeptic: a person inclined to question or doubt accepted opinions. "this argument failed to convince the skeptics"

Cooolone profile image
Cooolone in reply to Don_1213

Your diatribe has lost me, first Doctor Google reference, then ending with trying to give an English lesson...

Maybe some should check their ego...

So have a nice day!

Cooolone profile image
Cooolone in reply to Don_1213

.

2.2. Development and validation of a panel of 11 PCa-relevant genes

After the optimization of PCa-derived EV purification, a panel of mRNA markers reflecting the underlying malignancy was developed. The selection framework for these genes is shown in the Fig. 3a. First, to ensure the markers were highly specific to prostate rather than other tissues, 120 candidate genes were nominated on the basis of elevated expression in prostatic epithelium in contrast to 36 other tissues in The Tissue Atlas of The Human Protein Atlas. [27], [28] Eight genes specific to prostate tissue were selected by applying a threshold of a greater than 5-fold change when comparing prostate and non-prostate tissues. In parallel, to incorporate markers associated with metastatic PCa, the gene set from Miyamoto et al. [29] was considered given its use in a PCa liquid biopsy setting as blood-based biomarkers for detection of disseminated PCa. The six top expressed genes in their dataset (GEO GSE67980) were incorporated into the final panel. As 3 genes overlapped between the above gene sets, this process yielded 11 PCa-relevant genes, including ACP3, FOLH1, HOXB13, KLK2, KLK3, KLK4, MSMB, RLN1, SLC45A3, STEAP2, and TMPRSS2 (Supplementary Table 2). Since the majority of the background EVs circulating in cancer patient’s blood originated from immune cells, [30] it was crucial to ensure the selected genes are expressed at low levels in immune cells to minimize background noise. The expression level of these 11 genes was further evaluated in PCa tissues (from The Cancer Genome Atlas [TCGA]), [8] PCa cell lines (from Cancer Cell Line Encyclopedia [CCLE]), [31] and immune cells (from Differentiation MAP [DMAP]), [32] As shown in Fig. 3b, these 11 genes were highly expressed in PCa tissues and PCa cell lines, while lowly expressed in immune cells (P < 0.001, respectively), making them potential PCa markers for a blood-based assay.

Cooolone profile image
Cooolone in reply to Cooolone

And in closing...

We do recognize that there are limitations to the study as presented. First, due to the lack of comprehensive PCa EV-derived mRNA data in the current scientific literature or publicly available databases, the genes selected for the initial assay were selected from tissue-based datasets. These may not provide the most suitable candidates for an EV-based study. Thus, we conducted a PCa cell line-derived EV interrogation to confirm the applicability of this gene panel in EVs.

Don_1213 profile image
Don_1213 in reply to Cooolone

I don't understand your point.

witantric profile image
witantric

Is the test available or just in trials?

Don_1213 profile image
Don_1213 in reply to witantric

I suspect it's not even close to being an available test. The paper reports on the use of a novel technique for identifying different types of cancer cells being in the body. Taking the techniques they described into a machine for production use is going to require some monetary and engineering commitments from an analytics instrument company, then certifying it with the FDA (to get insurance coverage) then finally putting it into production and training lab technicians in it's use. All of these will take time, and will be driven by the finances involved.

BruceSF profile image
BruceSF

Hi, sorry to jump into this interesting conversation kind of late, but I was intrigued by the possibility of testing for micro-metastases so I took some time and read the paper. One thing i noticed was that they didn’t really run a test on 40 people. Rather, they used 20 localized and 20 metastatic patients to create a score that could discriminate between the two groups based on the 11 genes they were detecting in the mRNA. Then, they actually tested it on 3 people and followed them for a while. The two who tested as localized didn’t progress but the one who tested positive for micro-Mets did progress. So the test appears to have been accurate on 3 people

So this is more of a proof of concept than a real test. It appears that they have developed an improved way to analyze circulating mRNA and have used it to develop a score that looks like it might be useful, but I suspect someone will find a better set of genes and derive a better score on more patients and then test it on several hundred more before it finds its way into your local oncology clinic.

On the other hand, if your PSA is rising after RP and you can grab a slot in the trial at Mt Sinai, you could probably ask for 6 months of ADT + ABI, ENZA or APPA if it shows positive for micro-Mets

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