Around 9,100 people are diagnosed with oesophageal cancer each year in the UK. 

A big challenge with this type of cancer is that many people don’t realise there’s a problem until they start to have trouble swallowing. Often, these symptoms aren’t recognisable until a later stage in the disease.  

But there may be an opportunity to detect the disease earlier. Some people develop a condition – called Barrett’s oesophagus – prior to developing into cancer. 

Barrett’s oesophagus is much more common than oesophageal cancer, and although it will only become cancer in a handful of cases, it presents an opportunity for doctors to spot a problem early and intervene before cancer develops. But the typical test for Barrett’s oesophagus, endoscopy, is both invasive and expensive. 

Enter the Cytosponge.  

Cytosponge-TFF3 test is a ‘sponge on a string’ device coupled with a laboratory test called TFF3 developed by scientists funded by the Medical Research Council (MRC) and Cancer Research UK – a simple, quick and affordable test for Barrett’s oesophagus that can be done in a GP surgery.  

And the latest results, published in The Lancet, suggest this Cytosponge-TFF3 test can identify ten times more people with Barrett’s oesophagus than current GP care. 

We caught up with Professor Rebecca Fitzgerald, based at the University of Cambridge, whose team studies oesophageal cancer and has worked hard over the last decade to develop this innovative test.

How does it work?

Cytosponge is a small coated pill-on-a-string that contains the sponge. It’s easy for people to swallow, and when the pill reaches the stomach, the coating dissolves and the sponge expands.  

When the sponge is pulled back up, it collects some of the cells lining the oesophagus on its way. The sponge is sent off for analysis in the lab, “where we have developed a simple antibody test called TFF3 so that pathologists can easily spot the signs precancerous condition”.  

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Planting the seeds 

A seed was planted for the idea for the Cytosponge in around 2000, whilst Fitzgerald was still in London.  

“I was talking with my boss, Professor Mike Farthing, about how an endoscopy isn’t ideal for patients and for sampling, and how what you really need is some kind of bottle brush for easy collection of cells.”  

But it was when Fitzgerald moved her research to Cambridge in 2002 that she began a prototype for this ‘bottle-brush’ idea. Over the years, the prototype evolved into what’s now recognised as the Cytosponge, which has been tested on thousands of people across the country.  

The first real test for Cytosponge was to see if people were willing to try the sponge-on-a-string, and whether the process was feasible in a GP surgery.  

And once that hurdle was cleared, it was time to test the accuracy of Cytosponge in clinical trials.

The latest results  

The latest Cytosponge trial compared Cytosponge to the current model for managing people with heartburn symptoms, the main risk factor for Barrett’s and cancer of the oesophagus.  

“What GPs ordinarily do if you’ve got reflux symptoms is to give you medication to get rid of the heartburn. So, most patients that see their GP with heartburn won’t get an endoscopy test,” Fitzgerald explains.  

“Because the Cytosponge is such a simple test that you can do, basically in 10 minutes in a GP surgery, we wanted to compare what GP’s ordinarily do, with offering all patients who usually receive medication for heartburn the Cytosponge test.” 

13,000 patients were enrolled in the study from GP surgeries across England. Half of these patients were offered the standard clinical care, while the other half were offered the Cytosponge.  

At the end of the trial, the team analysed how many cases of Barrett’s oesophagus were picked up in each of the two arms of the trial, and the results were quite remarkable.  

“We found 10 times more cases of Barrett’s oesophagus in the people that were offered a Cytosponge compared with what GP’s ordinarily do,” says Fitzgerald.  

What’s more, the trial picked up a number of early stage cancers too.  

“If the cancer is detected early you can cure the disease. You can remove it completely at endoscopy and the patient may not need to have chemotherapy and surgery to remove the oesophagus,” Fitzgerald explains.  

The results will not only change the way Barrett’s oesophagus and oesophageal cancer is detected in the future, the success of the BEST3 trial has meant that cancers have been successfully detected and treated in those who took part.  

Liz is one of those cases.

Liz’s story 

Liz took part in the BEST3 trial in 2017.

Liz had suffered with acid reflux for many years. When she received a letter from her GP about the BEST3 trial, she signed up out of pure curiosity.  

“I was curious about the trial because I’d never heard of Barrett’s oesophagus and so I just took part out of interest,” Liz explains.   

A fortnight after having the Cytosponge test at her local GP surgery, Liz received a letter saying that the test indicated she did have Barrett’s oesophagus. Next, Liz required an endoscopy to clarify the results.  

“I went and had an endoscopy and even I could see that things were not very good in my oesophagus. It was extremely inflamed and bleeding and not healthy looking at all.”  

The endoscopy also revealed that she had early stage oesophageal cancer, “that was the moment when you suddenly think, oh, this is bad”.  

Thankfully, the cancer had been caught early by the Cytosponge. “I didn’t have to have any harmful treatments at all. They could remove it by doing an endoscopic resection,” says Liz.  

Liz is a retired scientist, who has experience of working in research labs. “I understood about a lot of the processes,” she explains, “there’s a huge amount of science behind it, but the procedure itself is so simple. It is, to my mind, a perfect test that could easily be carried out widely in the community.” 

This was in 2017, at the beginning of the BEST3 trial. Since then, Liz has been busy enjoying life to the full. “Last year, as well as enjoying a 90-mile walk along the Ridgeway, I was able to put my hobby of pottery to good use by making a hundred coasters bearing an image of the Cytosponge. These were sent as a small thank you gift to the research nurses involved in the BEST3 trial.”  

A COVID-response Cytosponge clinic 

The team recently received a grant to begin implementing the Cytosponge test, both in GPs and in secondary care across England in the coming years.  

But the onset of the coronavirus pandemic meant that plans were quickly adjusted. 

“COVID-19 means that endoscopy services were pretty much shut down,” Fitzgerald explains, “it means that there are people out there who just weren’t being referred, or who had been referred and were being stalled and not getting access to diagnostic tests.” 

The team received permission to begin procedures immediately, setting up a ‘COVID Cytosponge clinic’ at the Addenbrooke’s hospital in Cambridge.  

“We were taking patients referred by the two week wait from their GP,” says Fitzgerald. “These are people who can still swallow capsules, who don’t sound quite so poorly, but otherwise would have had a delay in getting the endoscopy, who got the Cytosponge test.” 

Cytosponge than had been tested in the previous trials, but analysing the data collected in this Addenbrooke’s pilot will help to find out if Cytosponge can play a useful role in working out who would benefit from an endoscopy the soonest.  

The Cytosponge test has reaffirmed the need to continue searching for innovative diagnostic tools, that detect pre-cancerous conditions quickly and non-invasively. One that can help save lives in today’s uncertain circumstances and into the future.   

Lilly

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