“Now this is not the end. It is not even the beginning of the end. but it is, perhaps, the end of the beginning.”

So said Winston Churchill in November 1942. He was of course talking about the Second World War. Today I am thinking about cancer. The launch of the NHS-Galleri trial does not mark the end of cancer as an important public health problem. It does not even mark the beginning of the end. But it is certainly a turning point in our ability to control cancer and reduce its devastating impact on society.

We don’t yet know that the Galleri test will have a role in cancer screening, but its potential to dramatically cut the numbers of people who die from cancer is enormous. Modelling suggests that annual screening with the Galleri test could prevent about 10% of all cancer deaths. That is why we are running the NHS-Galleri trial to find out whether an NHS screening programme using the Galleri test would live up to its potential.  We have seen with COVID-19 that randomised controlled clinical trials are essential. Many people, including world leaders and senior clinicians, thought that hydroxychloroquine would be a wonder drug in the treatment of COVID-19. The demand was so great as to cause a global shortage of the drug. But well controlled clinical trials showed that it was useless. By contrast, the RECOVERY trial showed that dexamethasone reduces the risk of dying from COVID-19 among hospitalised patients receiving respiratory support and over the last year this one drug has saved an estimated one million lives.

The Galleri test builds on numerous advances in molecular biology, genomics, biotechnology, and artificial intelligence. The test is looking at cell-free DNA in the blood. When cells die small fragments of their DNA can enter the blood stream. The same technology is now used in antenatal screening. Here one is looking for small fragments of DNA from a cancer that make their way into the blood. In antenatal screening, it is cell-free DNA from the foetus that is of interest. These DNA fragments don’t last long in the blood because they are cleaned up by macrophages.  Only a tiny proportion of blood is cell-free DNA and only a tiny proportion of that DNA will come from the cancer. What is more, since we are only talking about small fragments of DNA, most fragments from a cancer will be identical to fragments from a healthy cell. The challenge of identifying cancer from a blood sample is a little like trying to see if someone in your house is ill by sifting through your dustbins or taking a sample from the sewage. The Galleri test isn’t looking at the DNA directly. It looks at DNA methylation – that is the pattern of methyl groups attached to the DNA. There are so many different possibilities for DNA methylation that it requires sophisticated machine learning to identify and recognise the patterns caused by cancer.

Studies have already shown that the Galleri test can identify over 50 different types of cancer from a blood sample.  We know that it is only very rarely (about 1 in 150 or 1 in 300) positive in people who don’t have cancer. It is more likely to be positive for more advanced cancers; and it better at detecting some types than others. Overall, the test seems to find about half of all cancers, and it is positive in over 80% of advanced cancers.

In most of the clinical studies of the Galleri test to date, patients were known to have cancer before they were tested. So, we know the test “works” but we don’t know if it’s really useful – we don’t know for certain that the test will enable us to pick up cancers sufficiently early so as to make a difference to patients within the NHS. Mathematical modelling of tumour growth and progression suggests that annual screening with Galleri will make a big difference but the only way to be certain is to conduct a randomised controlled trial.

I have studied cancer screening my whole career. I was very lucky to have been involved in HPV testing research from very early on. Together with Jack Cuzick, I published a paper in 1997 suggesting that HPV testing could be introduced into cervical screening in a cost-effective manner; and in 2002 we suggested that it could replace cytology. But it was only in 2019 that HPV testing became the primary cervical screening test in England. I don’t want us to have to wait so long to find out whether the Galleri test could save lives and to see it introduced into the NHS.

Screening is expensive and it is not risk-free. Some people will be made anxious by positive tests when they don’t have cancer. Some people will have invasive testing for cancer that they might not have needed and suffer complications because of that testing. It is also possible that the test will find cancers that might never have been diagnosed or caused problems without screening. On the other hand, it is possible that annual screening with the Galleri test will prevent about half of all advanced cancers, avoiding toxic and expensive treatments and in many cases premature and painful deaths. That is why it is so important to find out if screening with the Galleri test really improves people’s health and, importantly, whether it can work within the NHS.

I, and many within the Cancer Prevention Trials Unit, are extremely excited to be playing a leading role in this revolutionary clinical trial. Many members of the team have worked incredibly hard over the last year to ensure that the trial is well run and delivers a definitive answer to this hugely important question. Preparing to invite around a million people and to take blood and randomise 140,000 is not a small task. We also want to ensure that the trial is welcoming and includes people from across the country and with a wide range of backgrounds. The team have planned to have the mobile clinics in rural, urban, and inner-city areas and have made arrangements for wheel-chair access and translators. It is important that participants have the best experience possible. Those who test positive will be referred promptly to an appropriate NHS clinic. The team have been working hard to make sure that participants find it easy to make appointments and to speak to someone who can answer any questions they may have.

As we launch the NHS-Galleri trial, and perhaps reach the end of the beginning in our quest to dramatically reduce the numbers of cancers diagnosed at advanced stage, I want to give a huge thank you to the team who have worked so hard to make sure the trial will be a success.

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