New oesophageal cancer screening trial begins testing the capsule sponge

The pivotal trial to determine whether we can use a quick ‘pill-on-a-thread’ test to screen people with chronic heartburn for early signs of oesophageal cancer is now underway. 

BEST4 Screening is the culmination of more than 20 years of research into the capsule sponge test, which was developed by Professor Rebecca Fitzgerald, director of the Early Cancer Institute at the University of Cambridge.  

Though it starts out as a pill, Fitzgerald’s invention changes into a small sponge after being swallowed. When it’s pulled back up with the attached thread, the sponge collects cells from the oesophagus (the food pipe) for lab testing.  

Previous trials have shown that the capsule sponge is much more effective at finding Barrett’s oesophagus, a rare condition that can lead to oesophageal cancer, than current options.  

The most common symptom of Barrett’s oesophagus is heartburn, so BEST4 Screening will give capsule sponge tests to 120,000 people in specific age groups who regularly take heartburn medication. With our funding, the trial will find out whether the capsule sponge test can help find more cases of Barrett’s oesophagus, prevent cancers and save lives as part of a national oesophageal cancer screening programme. 

“The capsule sponge is changing how we detect Barrett’s oesophagus and oesophageal cancer,” says Fitzgerald, one of BEST4’s two principal investigators. “Catching it earlier can save lives and reduce the need for chemotherapy and surgery to remove the oesophagus. 

“Thousands of people have already benefited in trials and pilot programmes, and now we’re taking the test to the next level to see if we could offer this to everyone with heartburn.”

Why we need to diagnose oesophageal cancer earlier

Roughly 1 person out of every 50 diagnosed with cancer in the UK has oesophageal cancer. It’s the 14th most common cancer across the country, with around 9,400 new cases each year.  

But those statistics don’t tell anything close to the full story. Oesophageal cancer kills a disproportionate number of people.  

This is linked to the fact oesophageal cancer often takes a long time to cause clear symptoms, so most people are diagnosed after it has already begun to grow and spread to other parts of their body. At that point, there’s much less doctors can do to treat it.  

As a result, oesophageal cancer causes 1 out of every 20 deaths from cancer. It’s the UK’s 7th leading cause of cancer death. 

But there’s a way to change that.

Many oesophageal cancers develop from Barrett’s oesophagus, so, by giving us a better way of identifying Barrett’s oesophagus, the capsule sponge test could put doctors in position to catch more oesophageal cancers early, when treatment is much more likely to be successful. The test could even give us a window to stop some oesophageal cancers developing in the first place.

The video below shows how EndoSign, the capsule sponge being used for BEST4, works:

Chronic heartburn, Barrett’s oesophagus and oesophageal cancer screening 

Barrett’s oesophagus is a rare condition where cells in the oesophagus start to look and act more like cells from the stomach. These cells are more likely to keep changing in ways that might lead to cancer than normal oesophageal cells.  

The most common symptoms of Barrett’s are heartburn and acid reflux. Usually, though, they don’t indicate anything dangerous. Without a simple test for checking whether heartburn could be linked to Barrett’s, doctors mainly focus on providing medication to relieve symptoms. 

“Most people with Barrett’s oesophagus have heartburn, but most people with heartburn don’t have Barrett’s oesophagus,” explains the other lead investigator for BEST4, Professor Peter Sasieni from Queen Mary University of London (QMUL). 

The current ‘gold-standard’ test for finding Barrett’s oesophagus is endoscopy, where a specialist threads a long tube with a camera on the end down a person’s throat and into their food pipe (or gullet). It’s too intricate, expensive and invasive for doctors to offer it to most people with heartburn or acid reflux, let alone for the health service to use it in a screening programme. 

The capsule sponge test, which takes just 10 minutes and can be carried out by a nurse, makes up for those issues. A previous clinical trial, BEST3, showed it picks up 10 times more cases of Barrett’s oesophagus in people with chronic heartburn than routine GP care. 

“We have already shown that the capsule sponge can reliably identify people with Barrett’s oesophagus,” continues Sasieni, who is the director of the Cancer Research UK Cancer Prevention Trials Unit at QMUL. “Now we need to show that using it in a targeted screening programme can help prevent oesophageal cancer and reduce deaths from this disease.   

“The BEST4 Screening trial is a huge undertaking which will take many years, but it’s important that we find out whether a new routine screening programme really will prevent cancers and save lives.” 

Designing and testing the capsule sponge

Together with the National Institute for Health and Care Research, we’re providing the £6.4m in funding needed to carry out such a large and complex trial. 

This month, the NHS started sending text messages encouraging eligible people (men over the age of 55 and women over the age of 65 who are currently taking medication for chronic heartburn) to take part. Participants will be asked to join Heartburn Health, a new platform for research into heartburn and its associated health conditions. Special mobile screening vans are also being rolled out across England to deliver the tests as conveniently and efficiently as possible. 

The trial’s logistics might be complicated, but it’s the capsule sponge’s simplicity that gives it so much potential. 

It starts off as a small, coated pill attached to a thread. Part one of the test is just swallowing the pill and waiting.  

When it reaches the stomach, the pill’s coating dissolves, releasing a small sponge, which expands to the size of a 50p coin. From there, a nurse or GP gently pulls the sponge out using the thread.  

The oesophageal cells it collects along the way are then sent to the lab, where they’re tested for Trefoil Factor 3 (TFF3), a protein only found in Barrett’s oesophagus, and altered p53 proteins, which identify cells which are starting to grow out of control and become oesophageal cancer. 

BEST4: a two-part trial

More than 24,000 capsule sponge tests have been performed in pilot programmes across England, Scotland and Northern Ireland in recent years. Some have already taken place in the first part of BEST4, BEST4 Surveillance, which launched in January 2024.  

That element of the trial is investigating whether the capsule sponge could replace endoscopies as a way of monitoring people who have already been diagnosed with Barrett’s oesophagus. It’s designed to compare the two tests as ways of checking for signs that Barrett’s might be developing into oesophageal cancer. The results will show us which is the best way to make sure doctors can intervene to stop or treat oesophageal cancer at the earliest possible opportunity.  

Previous pilots of the capsule sponge have also helped cut testing backlogs by allowing doctors to test patients who are currently on waiting lists for endoscopy, either because they have long-term heartburn or have already been diagnosed with Barrett’s oesophagus.

Transforming oesophageal cancer diagnosis

BEST4 Screening will be led from Cambridge University Hospitals NHS Foundation Trust (CUH) and the University of Cambridge. Like the previous capsule sponge trials we’ve funded, it was designed by the Cancer Research UK Cancer Prevention Trials Unit at QMUL, which will also analyse the study’s results. 

“Backed by funding from Cancer Research UK, the capsule sponge has become one of the most exciting early detection tools to emerge in recent years,” says Michelle Mitchell, our chief executive. “It’s a remarkable invention by Professor Fitzgerald and her team, and previous trials have shown how powerful it can be in identifying cancer earlier.   

“Cancer Research UK is proud to be supporting this landmark clinical trial, bringing the capsule sponge test into the community and offering it to a much wider group of patients. After many decades of research, we’re on the cusp of transforming oesophageal cancer diagnosis forever.” 

More information about how to join the trial can be found at https://best4trial.secureserversites.net/

Tim