There's 1-10 Circulating Tumor Cells (CTC) per mL of whole blood. So why liquid biopsies are not common?

[DarkEnergy]

The website link below is a good starter for understanding CTC.

- technologynetworks.com/diag...

A Google search reveals there's about 4500 to 5700 ml of blood in the average (150-180 lb) human body - so, do the easy math. Prognosis correlates with CTCs, according from a talk by Daniel Sabath, MD, PhD, University of Washington (Circulating Tumor Cells Circa 2020): "Cutoff of 5 cells per 7.5 mL blood for breast and prostate cancer" - are considered at a higher risk. The talk also shows CTC count as a better predictor of progression vs PSA.

Well, I've correlated this with other researchers' perspectives, always include my favorite, Dr Tanya B Dorff.

Dr Dorff's take, CTC count has not been proven (no clinical trials) for a progression indicator.

My point, as an PCa patient, physicians cannot be proactive, they will apply Standard of Care (SOC) treatment protocols and react to results.

To answer my question: "So why liquid biopsies are not common? ", because the results are not actionable!

[Hidden]

Great 👍 post. The best is I don't need to provide an answer to the question.

[Tall_Allen]

Exactly. What does one do with that info? What does it mean? Is it prognostic for anything?

[Gemlin_ in reply to Tall_Allen]

Couldn't one possible future clinical relevance be to identify surgery patients in risk/need of further treatment (before rise in PSA detected)?

[Tall_Allen in reply to Gemlin_]

CTCs don't show up until there are significant metastases.

[Gemlin_ in reply to Tall_Allen]

I saw this in Urology Times about a study in Korea. Doesn't it indicate that there could be a future potential for including CTC when giving post surgery prognosis? Can't be significant metastases if undetectable PSA?

“Circulating tumor cells in the blood were frequently detected in patients with undetectable prostate specific antigen levels after radical prostatectomy for localized prostate cancer. Furthermore, circulating tumor cell detection was associated with an increased risk of biochemical recurrence, suggesting that circulating tumor cell detection precedes prostate specific antigen rise after surgery in cases of prostate cancer recurrence. Large-scale validation is needed in the future,” the investigators wrote.

[Tall_Allen in reply to Gemlin_]

IDK - I wouldn't count on it. The data are equivocal. "Large-scale validation is needed in the future.” Currently, consistent correlations are lacking.

pubmed.ncbi.nlm.nih.gov/225...

pubmed.ncbi.nlm.nih.gov/250...

medscape.com/viewarticle/89...

"This means that one third of patients with mCRPC being treated with first-line therapy will not be assessable for the CTC0 end point...In the nonmetastatic CRPC setting, the proportion of evaluable men for the CTC0 intermediate end point will likely be even less, probably in the 50% range. Second, it is unclear whether this response marker is equally predictive of overall survival in men with low baseline CTC counts compared with those with higher counts. For example, a patient with a baseline CTC count of 1 dropping after 12 weeks to zero would be counted equally as a patient with a CTC count of 1,000 that drops to zero. Notably, the reproducibility of the CTC result in men with low baseline counts (eg, in those with < 5 CTCs) would be expected to be unreliable. Third, the EpCAM-based CTC capture method used by CellSearch has some disadvantages. For example, it is unknown whether all cells captured by this assay truly represent viable CTCs shed by the tumor versus other epithelial or necrotic cells, and, conversely, this assay will miss EpCAM-negative CTCs, which may be undergoing mesenchymal transition. A provocative approach that could theoretically overcome this limitation in the future would be to use presence or absence of tumor-specific cell-free DNA as an alternative efficacy response marker,13 although many questions about the analytical and test characteristics of these assays still exist at this time (and clinical qualification has not begun). Finally, because CTC0 is a response indicator rather than a time-to-event end point, it would have been comforting to see an analysis of the discriminatory power of the CTC0 end point in terms of its ability to predict objective response rates in those with measurable disease. A high discrimination for both radiographic response and survival would go further in supporting the biologic and clinical plausibility of this intermediate biomarker."

ascopubs.org/doi/10.1200/JC...

[tom67inMA]

To be fair, my liquid biopsy from Foundation One did recommend a couple of classes of off-label drugs, and about a dozen phase 1 trials that would be applicable to me based on my genetics, but nothing that seemed like a better idea for the time being than chemo.

Also, it just noted a very small number of mutations, whereas an experimental genetic panel at Dana Farber listed probably over a hundred "copy number variants". It turns out I'm entirely missing some rather important genes for stopping cell growth that weren't mentioned in the liquid biopsy. Again, no actionable results although my amateur opinion is that my cancer is best attacked by inflicting DNA damage, but DNA testing tends to promote newer treatments. There probably haven't been any studies as to what genetic changes imply whether docetaxel will be more or less effective, for example.

Oh, and if I had my genetic results earlier I might have saved the expense (to my insurance company) and side effects of atezolizumab which was unlikely to work based on lack of mutational burden.

[DarkEnergy in reply to tom67inMA]

When I was diagnosed with PSA 1000+, and told I had extensive "metastasis" based on the scan results. I was stunned, my only clinical issue prior was snapping my knee ACL when skiing in Utah.

Well, hit the web and learned CTC is the mechanism for metastasis and became fascinated. As you, invoked my amateur opinion machine and questioned why CTC count per whole blood mL makes a difference. Because I was diagnosed with tumors all over my pelvic and some in ribs, but with just ADT+, became PSA undetectable in short order. Then others have a few tumors, but cannot reach PSA undetectable.

So, while continuing my CTC amateur investigation, discovered some researchers use "Circulating Tumor DNA", this made much more sense. Hey, I'm just an inquisitive PCa patient like you...

By the way, I've had some pre-med student friends taking CS minor course struggling with C++ doubly linked list copy constructor assignment.

[tom67inMA in reply to DarkEnergy]

DNA has a lot to do with cancer behavior. As an example, my cancer is missing several genes that cause cells to stick to each other, thus circulating tumor cells and lots of metastases.

Cancer aggressiveness and susceptibility to treatment are separate issues. We both seem to have aggressive cancers that respond to treatment. Others have slow growing cancers that resist a number of treatments. Does anybody remember Whatsinaname? Basically nothing worked for him. He was a nice guy, I miss him.

[Hidden in reply to tom67inMA]

I'm not missing..I've been here the whole time.😁

[MateoBeach]

Two reasons I can see fir liquid biopsy. 1) to obtain genetic profile when there are no biopsy accessible mets. Foundation One results are 90% concordant from CTCs. 2) as a possible marker for progression with PC variants that produce little to no PSA such as neuroendocrine etc.

[DarkEnergy in reply to MateoBeach]

Do you have information regarding Foundation One's dataset accuracy for concluding actionable results? I'm not aware of a global Advance Prostate Cancer data registry.

[MateoBeach]

No not a global database. Just that 4 poster abstract presentation at this month’s ASCO GU meetings showed about a 90% correlation, both for positive and for negative gene findings between biopsies tested and CTCs in the same patients. That only suggests that CTC Foundation One results are comparable to solid biopsy results.

[6357axbz]

Findings from a Phase III Clincal Trial

“ So, we conclude from this study that baseline CTC counts were indeed highly prognostic of PSA response and progression in this cohort of men with metastatic castrate-sensitive prostate cancer who were just starting their therapy with hormonal treatment”

medpagetoday.com/meetingcov...