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Detection of a pre-cancerous throat condition called Barrett’s oesophagus can be improved with the use of an innovative swallowable sponge and laboratory test, a large multicentre trial found.
Heartburn, caused by acid reflux from the stomach up into the gullet (oesophagus), is common among people visiting their GP. It is usually treated with acid suppressants. But acid reflux can lead to Barrett’s oesophagus, which in turn increases the risk of oesophageal cancer.
GPs may send people with heartburn for an endoscopy. It is an awkward procedure but, at present, is the only way to diagnose Barrett’s oesophagus. As a result, most people with Barrett’s are not diagnosed and do not benefit from early treatment when cancer starts to develop.
In the new study, people with heartburn instead swallowed a capsule attached to string. The dissolvable capsule contained a fluffy sponge that GPs then pulled out of the stomach, up through the oesophagus and out of the patient’s mouth to retrieve cell samples. Analysis of these cells under a microscope for a marker called TFF3, developed by the same team, could find tell-tale signs of Barrett’s oesophagus.
The research found that the test – called Cytosponge-TFF3 – could help GPs narrow down which people with heartburn should be sent for an endoscopy.
What’s the issue?
In Barrett’s oesophagus, cells lining the oesophagus have changed as a result of acid reflux. It is not cancer, but it does slightly increase the chance of cancer developing. People diagnosed with Barrett's oesophagus have regular tests to make sure signs of cancer are found early and treatment started promptly. Unfortunately, four in five cases of Barrett’s oesophagus go undiagnosed.
Endoscopy means a tube with a camera on the end being passed down the throat. Samples of cells from areas that do not look normal are taken and examined to make a diagnosis. But endoscopy can be uncomfortable and has some risks associated with sedation.
A common symptom of Barrett’s oesophagus is heartburn. At present, GPs have no easy way of checking such patients for Barrett’s oesophagus, so they send many people who complain of heartburn for an endoscopy. This is expensive, time consuming and unnecessary in 19 out of 20 cases. A tool that would help GPs identify and prioritise those patients who do show signs of Barrett’s oesophagus would be valuable.
The randomised trial was carried out in 109 GP practices across England. It included more than 13,000 patients aged over 50 who had been on heartburn medication for six months or more. Half received usual care, and the rest were given the option of the Cytosponge to help the GP decide if they needed an endoscopy (they could refuse and opt instead for the normal care). The trial compared how many patients from each group were diagnosed with Barrett’s oesophagus within twelve months.
The results showed that:
- The procedure was acceptable to many. Two in five people who were offered the Cytosponge expressed an interest (39%; 2679 of 6834 people)
- Two in three of those who expressed an interest in the Cytosponge underwent the procedure (65%; 1750 of 2679)
- Almost all swallowed the Cytosponge successfully and produced a cell sample for analysis (95%; 1654 of 1750)
- Just one in 30 of the patients offered the Cytosponge were referred for an endoscopy (3%; 231 of 6834)
- The Cytosponge improved diagnoses. Ten times as many people offered the Cytosponge were diagnosed with Barrett’s oesophagus, compared with the usual care group
- Nine of those offered the Cytosponge were diagnosed with signs of early cancer, compared with no early cancer, only advanced disease, in the usual care group
- There were few side effects of the procedure; the most common was a sore throat.
The findings suggest that the Cytosponge was a useful aid to GPs in deciding which people to send for endoscopy. It increased the numbers diagnosed with Barrett’s oesophagus and with cancer.
Why is this important?
Oesophageal cancer can be treated more easily and successfully if the disease is caught early. At this stage, cancerous cells can be removed by endoscopy. But many patients are not diagnosed until the cancer is advanced, when treatment involves chemotherapy and surgery. So, a reliable screen for the early signs of the disease could save lives and reduce the need for severe and expensive treatments.
The new study shows that the Cytosponge could serve as a screening tool for early cancer. Ten times as many cases of Barrett’s oesophagus were found in the patients offered the procedure. The results imply that nine in ten cases in the usual-care group were missed – perhaps storing up trouble for later years.
The results show that, in principle, GPs could use the Cytosponge to quickly screen patients with heartburn and identify those most in need of an endoscopy and possible further treatment.
However, widespread use of the Cytosponge is likely to increase the number of patients sent for endoscopy. That increases the chances of over-diagnosing Barrett’s oesophagus (identifying changes to cells that would not progress to cancer) and causing unnecessary concern among some people .
Restrictions on the use of endoscopy during the COVID-19 pandemic mean the Cytosponge is already available in hospitals in Scotland. The research team argue it would have most benefit if offered as a screening tool in primary care settings such as GP surgeries. For that to happen, they need to analyse the costs and economic benefits, and to explore the reasons why, in the study, more than half declined the procedure. They are looking at different ways to describe and explain it.
The team is training a computer to spot the unusual cells that indicate a case of Barrett’s oesophagus. Machine learning would reduce the burden on individual oncologists and allow the process to be scaled up and automated.
The researchers are also working to enhance the technique and use laboratory tests in addition to TFF3 to identify the patients with Barrett’s who are most at risk for cancer. They are also exploring whether nurses in other community settings, such as pharmacies or mobile vans, could carry out the procedure.
You may be interested to read
The full paper: Fitzgerald R, and others. Cytosponge-trefoil factor 3 versus usual care to identify Barrett's oesophagus in a primary care setting: a multicentre, pragmatic, randomised controlled trial. Lancet 2020;396:333-344
Comment on the findings: Hanada Y and Wang KK. Screening for Barrett's oesophagus: is now the time? Lancet 2020;396:292-293
An economic evaluation of the use of the Cytosponge for Barrett oesophagus: Swart N, and others. Economic evaluation of Cytosponge®-trefoil factor 3 for Barrett esophagus: A cost-utility analysis of randomised controlled trial data. EClinical Medicine 2021;37:100969
Funding: The study was funded by Cancer Research UK, the NIHR, the NHS, Medtronic, and the UK’s Medical Research Council.
Conflicts of Interest: Two authors are named on relevant patents. Several hold shares and have received fees from associated companies.
Disclaimer: NIHR Alerts are not a substitute for professional medical advice. They provide information about research which is funded or supported by the NIHR. Please note that views expressed in NIHR Alerts are those of the author(s) and reviewer(s) and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care.