A cancer can spread through the body in a number of ways. The earliest spread is by direct extension. As the tumour grows it invades nearby tissues and organs causing damage and dysfunction. However, the most dangerous mode of spread is through the vascular system including the lymphatic system.

Here the cancer cells find a network of roads and means of transportation that can carry them throughout the body. They literally go with the flow.

To do this, they first have to detach themselves from the primary tumour and enter the circulatory system. This is not just a question of pushing themselves forward. Every property or function of a cell is determined by its genetic programme, pretty much like a computer programme determines the functioning of a computer.

To enter the circulatory system, a cancer cell first has to acquire the biological properties that allow it to do so. This it does by acquiring the right genetic programme. Without the right “invasion” programme it cannot do this. Genetic programmes develop and change through mutation.

So far so bad, but once inside the circulatory system it then must get out to reach its final destination and give rise to a secondary tumour, the dreaded metastasis.

Most people who die of cancer do so because of metastases. Virtually nobody dies of a breast lump unless this is so badly neglected that it causes complications like severe bleeding or infection by which time it would probably have spread anyway.

Much less commonly death can be caused without metastases by the local growth of a cancer. A brain tumour typically does this without generating metastases and a laryngeal cancer can cause asphyxia without significant spread.

This however does not mean that these cancers are not discharging cells into the circulation.

The new technology that has gone into the development of multi cancer early detection tests gives a new insight into the behaviour of cancer cells.

A random blood test can pick up and diagnose cancer cells in the blood from a wide variety of cancers even when they are undetectable by any other screening investigation.

 The first thing this tells us is that the quantity of cancer cells that enter the blood stream is truly mind boggling. The second thing it tells us is that this process goes on even with cancers that very rarely metastasise. The third thing it tells us is that happily very few cancer cells that enter the circulation actually give rise to secondary cancers ie successful metastases.

We would say that someone with a hundred identifiable metastases has very advanced cancer and is pretty much in an extreme situation. And yet this would represent a very small fraction of the number of cancer cells released into the circulation.

So, what’s happened to the rest of them? On average these cells have a life span of between 1 and 2.5 hours in the circulation. Then they are destroyed apart from those deadly few that get out. Even then the proportion of those that do get out and manage to grow into dangerous secondary tumours, remains very small. The very large majority of cancer cells that get into the circulation are destroyed. They either commit suicide ie they self-destruct a process called apoptosis, or else they are destroyed by the immune system. Both processes are not only highly complex but also tightly regulated.

What then allows a cancer cell to survive when most do not? The answer lies in its genetic programme and I suspect as with everything in life an element of luck. The successful cancer cell must have a few properties. First it must find a (genetic) way to escape the normal growth control mechanisms. Secondly it must acquire properties that block the natural self-destructive programme of an abnormal cell ie be resistant to Apoptosis. Third, it must avoid destruction by the immune system.

There are others like its ability to enter the circulatory system and its ability to exit it, but for the purposes of this article I will stop here and return to the second point, namely its resistance to apoptosis.

One must bear in mind that for any one of the commoner cancers to reach a readily detectable size of 1cm, it would have been growing for ten years or more- Stephen Brincat

This property has been used in at least one multi cancer early detection test. A random blood sample is used to detect the presence of cancer cells in the circulation. The cells in the blood sample taken are treated with an agent that would normally cause apoptosis even in normal cells. The apoptotic resistant cancer cells survive and can be selected out to make a diagnosis not only of cancer, but in a high percentage of cases, where that cancer originated eg breast or colon or cervix etc. What is even more amazing is that these tests can diagnose tumours like brain gliomas that do not usually metastasise.

A negative test has a sensitivity of around 88 per cent and a positive test a specificity of around 96 per cent. This means that a positive test tells us that there is almost certainly a cancer in the body and a negative test is slightly less certain that there is not, though still highly accurate especially when compared to other screening tests. This does not mean that these tests should replace the standard screening tests like mammography or cervical smear tests, at least certainly not just yet. They are a new weapon in our armamentarium.

The very high level of detection may in fact be a problem. The fact that most cancer cells in the circulation are destined to die and therefore not cause any problems raises the issue of whether a positive test that identifies cancer necessitates treatment. One may think that if there is a cancer in the body then it can hardly be ignored. This is true. It would necessitate further investigation to locate the primary cancer. In about three per cent of cases who are asymptomatic, and negative for all other screening tests, no cancer will be found. This creates a quandary. Not finding a cancer does not mean it does not exist but equally finding cancer cells in the blood does not automatically mean that that person will need treatment.

In most cases when a positive test leads to identification of a cancer the decision whether to treat or not will probably be more straight forward.

But one must bear in mind that for any one of the commoner cancers to reach a readily detectable size of 1cm, it would have been growing for ten years or more. During this time, it would be shedding cells into the circulation and paradoxically it is more likely to do so early in its life history rather than late. What this means is that we can have a positive test many years before we can detect a cancer by other means even if the test tells us where the primary is likely to be. This is not necessarily a good thing.

These tests exist and are locally available, but we still need to gain the experience and increased knowledge to know where they will fit in our management of this common and dreaded disease.

What we can say for sure is that when it comes to outcomes, we have made more progress in prevention and early diagnosis than we have in treatment and the increasing understanding of the biology of cancer tells us why this is so. Cancer has an evolutionary head start on us of several hundred millions of years but we are catching up.

Dr Stephen Brincat is director of oncology services, Saint James Hospital.