At what cancer stage do tumors release circulating tumor cells into the blood?

Question

And would a very accurate sensitive system for detecting circulating tumor cells (which detects 1 cell per 50 billion) be useful as a screening tool ?

Answer 1

Tumour cells can also metastasise using the lymphatic system. They first need to detach (produce enzymes that break down the extracellular matrix or any adherent molecules etc). Then they need to survive in the blood which is really hard with all the mechanical stress of being pushed around, the completely different nutrients, the different levels of blood gases, the immune cells in the blood and numerous filter mechanisms, then to truly metastasise they need to settle down somewhere and grow in their new environment. That's a lot of things right? So a sensitive assay like one you describe would need to have that tumour cell in the sample (unlikely, and only one cell is required to make a new tumour), is likely to be unable to tell that the cell is a tumour cell, wouldn't be able to differentiate between tumour cells that could or couldn't survive in the blood or differentiate those that could then go on to grow more in a tissue or not. And of course you're missing the entire lymphatic system. Following all of that, why does it matter? See a cancer, cut it out if you can and give chemotherapy to get rid of any possible cells outside of what you cut. If your assay came back negative or positive, treatment wouldn't change.

Answer 2

Screening programs are ruled out following sharp guidelines, like the so-called Wilson' criteria and subsequent ones provided by WHO. Specific documents regarding cancer screening have been published. A good primer on what a screening program in medicine is, can be found on wikipedia.

Conventionally, a tumor is considered non capable of metastasis (neither through blood, nor through lymphatic vessels), unless it doesn't invade the basement membrane, that is a thin layer of tissue that separates epithelias from the underlying tissues. In invasive neoplasiae, the surgeon have to cut it until the resection margins are free from tumour cells. This is achieved through real time microscopical examination by a pathologist during the procedure. If an ideal resection can't be performed, often medical therapy (e.g. chemotherapy) is suggested to the patient as neoadjuvant therapy. A neoadjuvant therapy is given in order to transform non optimal resectable tumors in good surgically treatable ones.

Commercial kits like this 1 , 2 , 3 , 4 are available on the market for this kind of test. Although there are this kit to find this cells, this method is not suitable for screening.