‘Pill-on-a-thread’ could replace endoscopies for half of all patients being monitored for esophageal cancer risk

(Press-News.org) Endoscopies could be replaced by far less invasive capsule sponge tests for half of all patients with Barrett’s oesophagus, a known precursor to oesophageal cancer, according to a new study from researchers at the University of Cambridge, Addenbrooke’s Hospital and Queen Mary University of London.

The capsule sponge test is easier to administer and could be carried out by nurses and at GP practices, reducing the burden on NHS resources.

Oesophageal cancer is difficult to treat, with fewer than one in five patients surviving for five or more years following diagnosis, a figure that has barely changed over the past three decades. At the same time, the number of people diagnosed with the disease has increased four-fold since the 1970s.

Barrett’s oesophagus One of the known risk factors for oesophageal cancer is a condition known as Barrett’s oesophagus, characterised by changes in the shape and structure of cells in the lining of the food pipe (the oesophagus). At first, these cells change to resemble those in the lining of the intestines, but over time they can change to a pre-cancerous state known as dysplasia.

Dysplasia may be low-grade or high-grade. Patients with low-grade dysplasia have around a one in 10 chance of developing oesophageal cancer, but this risk doubles to one in five for high-grade dysplasia. Dysplasia can be treated without surgery, and treatment greatly reduces the risk of future cancer.

Barrett’s oesophagus is usually diagnosed after a patient reports symptoms such as persistent heartburn and receives an endoscopy, an invasive procedure that involves passing a camera down into the stomach. However, there are long waiting times for initial endoscopy investigations on the NHS.

Patients diagnosed with Barrett’s oesophagus will be monitored to look for dysplasia or early cancer, undergoing regular endoscopies – often 10 or more over their lifetime. Catching the cancer early increases the chances of successful treatment and when the treatment can be performed down the endoscope as a day-case without requiring chemotherapy or an operation.

Professor Rebecca Fitzgerald, Director of the Early Cancer Institute at the University of Cambridge and honorary consultant gastroenterologist at Addenbrooke’s Hospital, who specialises in Barrett’s oesophagus, said: “It’s extremely important to monitor patients so that we can catch the dysplasia and prevent it developing to cancer – and if someone is unfortunate enough to develop cancer, we can catch it early and treat it.

“But the chances of Barrett’s progressing to cancer are low, and endoscopies are not very pleasant procedures. Added to that, endoscopies are not always a reliable way of spotting early cancers and can depend on the skill of the person doing the endoscopy and the equipment being used. What we need is an alternative surveillance method that’s less invasive, easier to administer and more reliable.”

A replacement for endoscopy? In recent years, Professor Fitzgerald and colleagues have developed the capsule sponge as an alternative to the endoscope. It involves the patient swallowing a pill connected to a thread. The pill dissolves in the stomach to release a sponge, which, when drawn back up, lightly scrapes off some of the cells in the oesophagus.

Samples from the capsule test are stained with a chemical and examined under a microscope. Pathologists look for two key markers – ‘red flags’ that suggest the cells are pre-cancerous. These are: abnormalities in a protein (known as p53) that helps to prevent tumours developing; and cells that appear abnormal or irregular when examined under a microscope (‘atypia’).

Most of the research to date on the capsule sponge has focussed on diagnosing Barrett’s oesophagus. But now, Professor Fitzgerald and her team have turned their attention to monitoring it more effectively with this device.

Stratifying patients according to risk In research published today in The Lancet, Professor Fitzgerald and colleagues looked at whether it was possible to use the capsule sponge to stratify patients with Barrett’s oesophagus according to their risk and use this information to determine how they are monitored. Those at highest risk would be seen urgently to see if they need treatment and those at moderate risk would continue to receive endoscopies, but those at lowest risk could continue to be monitored without the need for another endoscopy.

The team recruited 910 patients from 13 hospitals across the UK, all of whom had been diagnosed previously with Barrett’s oesophagus, and who were undergoing surveillance.

The patients were administered the capsule test, and based on the result, were assigned to one of three groups: high risk, moderate risk, or low risk. All patients also received an endoscopy, and their capsule sponge results were compared with their endoscopy results.

Around 15% of patients were classed as high risk, meaning that they had abnormal p53 and/or atypia. 38% of these patients were found to be at a pre-cancerous stage. Patients with both markers were at the highest risk – 85% of these patients were at a pre-cancerous stage.

Patients with neither of the two markers, but whose Barrett’s oesophagus was over a certain length and who met other risk factors related to age and sex, were classed as moderate risk.

Over half of the patients (54%) were classed as low risk. These were patients who had neither of the two markers and did not meet other risk factors related to age and sex. Endoscopy revealed that just two of these 495 patients – 0.4% - had a high-grade dysplasia that needed follow-up (and there were no cancers).

Professor Peter Sasieni from the Cancer Research UK Cancer Prevention Trials Unit, Queen Mary University of London, said: “Our findings suggest that the capsule sponge could help stratify patients with Barrett’s oesophagus by risk and that half of them will fall into the low-risk group. Given that the risk of these individuals progressing to dysplasia and then to oesophageal cancer is so low, it should be safe to replace their usual endoscopy with the capsule sponge.”

First author Dr W. Keith Tan, Honorary Registrar in Gastroenterology and Hepatology at Addenbrooke’s Hospital said: “Our ability to identify patients at low versus high risk using the capsule sponge – which may be as accurate as the current gold standard, endoscopy – is a great step forward. The capsule sponge can be administered easily and quickly by nurses with only limited training required and will not need to take up precious endoscopy resources, which may be better for patients and more cost-effective for the NHS.”

Professor Fitzgerald, who is also a Fellow at Trinity College, Cambridge added: “We are very excited by these results, which could lead to a test that is much more accessible and less operator dependent to improve standards for monitoring for patients with Barrett’s across the NHS and beyond.”

The study was supported by Cancer Research UK, Innovate UK, NHS England Cancer Alliance, and Medical Research Council, with infrastructure support from the National Institute for Health and Care Research Cambridge Biomedical Research Centre and the Experimental Cancer Medicine Centre.

Chief Executive of Cancer Research UK, Michelle Mitchell, said: “Survival rates for oesophageal cancer have remained unacceptably low for decades, with fewer than 20% of patients surviving for five or more years after diagnosis. Early detection is vital if we are to change this grim statistic.

"The Cancer Research UK–backed capsule sponge represents one of the most promising breakthroughs in early detection we have seen to date. These new findings bring us closer to transforming the way we diagnose and ultimately treat this disease. If adopted widely, this innovative approach could spare significant numbers of people from discomfort and invasive endoscopies. By bringing this more accessible alternative into community care, we have the potential to save more lives.”

“It’s much better than going for endoscopies”: Duncan Cook, 57 Duncan Cook, aged 57, a plumbing and heating engineer from Cambridge, participated in the research. For almost 20 years, Duncan has had regular endoscopies to monitor his Barrett’s oesophagus. He welcomed the results.

“I have a busy job and being able to have the sponge instead of an endoscopy would be much easier and save a lot of time.

“The first time I had the sponge, I was a bit nervous. It’s quite a big pill to swallow, but it’s much better than going for endoscopies. The sponge test is faster, you don’t need sedation for it, and you don’t need to find someone to come with you to drive you home after. I was able to have the test done and go right back to work after.”

Cambridge Cancer Research Hospital The University of Cambridge and Addenbrooke's Charitable Trust (ACT) are fundraising for a new hospital that will transform how we diagnose and treat cancer. Cambridge Cancer Research Hospital, set to be built on the Cambridge Biomedical Campus, will bring together clinical excellence from Addenbrooke’s Hospital and world-leading researchers at the University of Cambridge, including Professor Fitzgerald’s work, under one roof in a new NHS hospital. It will enable the development and discovery of more non-invasive devices like the capsule sponge, to detect cancer earlier, and save more lives. Find out more here.

Reference Tan, WK et al. Biomarker risk stratification with capsule sponge in the surveillance of Barrett's oesophagus: Prospective evaluation of UK real-world implementation. Lancet; 23 Jun 2025; DOI: 10.1016/S0140-6736(25)01021-9

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