Capsule sponge testing and oesophageal cancer diagnosis

The capsule sponge, also known as ‘pill on a string’, has been developed over the last 20+ years by Cancer Research UK funded researchers to help detect oesophageal cancer and its pre-cursor condition, Barrett’s Oesophagus, earlier.

Late-stage diagnosis of oesophageal cancer is common, with diagnostic challenges including non-specific symptoms that overlap with more common benign conditions. If detected at an earlier stage, oesophageal cancer survival is higher, with 63% of people diagnosed at stage 1 surviving for 5 years or more [1]. Improving pathways to diagnosis, including identification of Barrett’s oesophgus, may have a positive impact on timelier and earlier diagnosis of oesophageal cancer.

There are now several different capsule sponge technologies in use, including Cytosponge and Endosign. The device is used to sample cells from the lining of the oesophagus before they are tested for cell changes that may be a precursor to oesophageal cancer. 

Capsule sponge testing has the potential to improve patient experience and endoscopy (including gastroscopy) capacity. Studies are underway across the UK to evaluate capsule sponge testing in different use cases. 

For more information about the recognition and referral of oesophageal cancer, see our two-page oesophageal cancer insight guide for health professionals in England and Wales.

 

Read our guide

How do capsule sponge tests work?

The kit includes a small capsule containing a sponge attached to a surgical string. The patient swallows the capsule, which dissolves in their stomach. The sponge is retrieved by the health professional after a few minutes by pulling on the string. As the sponge moves up through the oesophagus it collects cells from the oesophageal lining which are analysed by pathologists in a laboratory for markers of Barrett’s oesophagus or oesophageal cancer. The test can be performed by trained professionals (eg nurses) in a community setting.

Watch this video to see how the test is performed:
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Advantages and disadvantages of capsule sponge

Advantages

 

Capsule sponge testing may improve patient experience, which could reduce did not attend (DNA) rates along the pathway. Compared to gastroscopy it is less invasive, quicker, does not require sedation and can be performed in a community setting.
It can be performed by different types of health professionals, including doctors and nurses. 

 

High levels of patient and clinical acceptability have been reported [2,3].
Pilot results demonstrate the potential of the capsule sponge to reduce endoscopy workload, by identifying those at low risk of Barrett's Oesophagus or oesophageal cancer and removing them from endoscopy wait lists. 

 

Capsule sponge has been reported as more cost-effective than standard  care in evaluations. 

 

 

Disadvantages

 

Adverse effects have been reported, including abrasion, incomplete swallowing, sore throat and detachment of the capsule sponge.

Data suggest that Barrett’s oesophagus may be missed in 19-27% of those with a negative capsule sponge result [2,4]. Safety netting those with a negative capsule sponge result but concerning symptoms is vital.
The device is not designed to detect stomach cancers, which present similarly to oesophageal cancers and could be missed if follow up endoscopy is not indicated.  
There is limited evidence demonstrating that capsule sponge could be used as a tool to detect oesophageal cancer earlier or that it improves oesophageal cancer outcomes.

Use cases for capsule sponge

The capsule sponge test is being evaluated nationally in three different use cases: 

  • Triaging patients with reflux symptoms waiting for gastroscopy in secondary care 

  • Surveillance in people with Barrett’s oesophagus 

  • Targeted or proactive case-finding of Barrett’s oesophagus in people at high risk in a primary or community care setting 

The image below shows these applications of capsule sponge across the diagnostic pathway for oesophageal cancer. 

Pathway infographic depicting capsule sponge use cases

Capsule sponge pilot studies and national evaluations across the UK  

Click the blue boxes below to find out more about different evaluations capsule sponge testing across the UK.

National evaluations have been completed in England (2021-2023) and Scotland (2020-2023) (links are external).

Key findings:

  • There was a significant reduction in endoscopy demand (by 78% in England and 77% in Scotland).  
  • The test is deemed safe and acceptable. No adverse events were reported and data suggest high patient and clinician acceptability.
  • Both evaluations demonstrated cost savings in comparison to usual care. 
  • Data from the evaluation in England showed there were relatively long wait times between capsule sponge test completion and the patient receiving their results. This reduced from a median of 55 days to 43 days throughout the evaluation. 

Areas that require further evaluation and research:

  • The diagnostic accuracy of capsule sponge for the detection of oesophageal cancer.
  • How the use of capsule sponge may impact patient outcomes.
  • How capsule sponge testing may impact inequalities in access to investigations and care.

Capsule sponge is now being used routinely in the NHS in Scotland to investigate and triage people with reflux in secondary care. In England, funding is available to support service development and implementation via Cancer Alliances. Find out more in our 'What’s next?' section.

Several teams across the UK are evaluating the use of capsule sponge testing for surveillance of Barrett’s Oesophagus. To date, Scotland is the only UK nation to have published evaluation data on capsule sponge use in Barrett’s oesophagus surveillance.

This evaluation reported: 

  • significant reduction in endoscopy demand
  • that capsule sponge successfully identified high risk patients for further investigation
  • evidence of reduced waiting times for high-risk patients between final surveillance endoscopy and start of treatment.
  • that cost-savings were identified compared to usual care.

Following the national evaluation, Scotland announced that capsule sponge testing will be introduced across all mainland Scottish health boards for the surveillance of people with Barrett’s oesophagus. It is currently implemented in five health boards.

Currently, gastroscopy is still the gold standard diagnostic test used for surveillance in people with Barrett’s oesophagus [5]. 

In 2023, NICE published guidance which concluded that the evidence base was insufficient to determine whether capsule sponge testing is suitable for surveillance in people with Barrett’s oesophagus [6]. Additionally, the European Society of Gastroenterology found low quality evidence for the use of non-endoscopic tools, such as capsule sponge, for Barrett’s oesophagus surveillance[7]. 

See the links below for more information about the national evaluations: 

Pilot projects as part of CYTOPRIME2 (link is external) are underway in some areas of England to evaluate capsule sponge in primary and community care settings to proactively identify and test those at higher risk of Barrett’s oesophagus and oesophageal cancer. The DELTA Project (link is external) also aims to use Cytosponge for proactive case finding in people with gastrointestinal reflux. Results are not publicly available for these projects yet.

BEST4 (2022-2035) (link is external), jointly funded by Cancer Research UK and the National Institute for Health and Care Research, will explore if capsule sponge testing can prevent deaths from oesophageal cancer when offered as a screening test to people on long-term medication for heartburn.

In 2023, the European Society of Gastroenterology recommended that capsule sponge can be used as an alternative to endoscopy for case finding of Barrett’s oesophagus [7].

Implementing capsule sponge for proactive case-finding could increase workload pressures in primary care and diagnostic centres, which would need to be considered alongside the potential benefits.

What’s next for capsule sponge?

A range of activity is needed to support the implementation of capsule sponge testing into practice, as sufficient evidence becomes available. 

Research and evaluation

  • Evaluations should be published in a timely manner and should outline clear recommendations, next steps and who is responsible to action those.
  • There is a need for clinical guidance to outline how capsule sponge testing could be integrated into health systems.
  • Further real-world data is required to evaluate capsule sponge testing in practice, focusing on how capsule sponge testing improves patient outcomes.
  • Further research to assess and compare different capsule sponge devices if needed, to reduce the potential risk of bias in existing studies.

Health system preparation

Capsule sponge testing is being rolled out across all health boards in Scotland. There isn’t a pathway for capsule sponge implementation yet in Wales and Northern Ireland.

In England, there’s no national funding stream for capsule sponge testing, but funding is available to support Cancer Alliances to integrate capsule sponge into their service. NHS Trusts can work with their local Cancer Alliance to write a business case and explore funding options. Guidance is available on Future NHS.

In all nations, health systems can take the following steps to prepare and ensure that future activity is successful: 

  • Ensure clinicians are fully informed of any changes to pathways.
  • Ensure that referral forms include capsule sponge if available.
  • Capsule sponge results should be integrated in Electronic Health Records.
  • Consider the required estates and equipment to integrate alternative diagnostics.
  • Provide clinical guidance to support practice.
  • Continued local and national evaluation of the intervention to ensure best practice is implemented.

Health systems should also engage with each other to share learnings to ensure implementation is effective.

Innovation

Evidence is emerging to assess how Artificial Intelligence (AI) deep-learning models might be used in analysis of samples collected during capsule sponge testing. AI has the potential to support pathology services by reducing demand on the workforce and improving efficiency [10-13]. Further research is required to assess the appropriate role/s AI could play in the detection of Barrett’s oesophagus and oesophageal cancer. 

References

  1. NHS England, Cancer Survival in England, cancers diagnosed 2016 to 2020, followed up to 2021 
  2. Kadri SR, et al. Acceptability and accuracy of a non-endoscopic screening test for Barrett’s oesophagus in primary care: cohort study. BMJ. 2010 Jan 25;341(sep10 1):c4372–2.
  3. Fitzgerald RC, et al. Cytosponge-trefoil factor 3 versus usual care to identify Barrett’s oesophagus in a primary care setting: a multicentre, pragmatic, randomised controlled trial. The Lancet [Internet]. 2020 Aug 1;396(10247):333–44.
  4. Ross-Innes CS, et al. Evaluation of a Minimally Invasive Cell Sampling Device Coupled with Assessment of Trefoil Factor 3 Expression for Diagnosing Barrett’s Esophagus: A Multi-Center Case–Control Study. Franco EL, editor. PLOS Medicine. 2015 Jan 29;12(1):e1001780
  5. di Pietro M and Fitzgerald RC. Revised British Society of Gastroenterology recommendation on the diagnosis and management of Barrett’s oesophagus with low-grade dysplasia. Gut. 2017 Apr 7;67(2):392–3.
  6. Barrett's oesophagus and stage 1 oesophageal adenocarcinoma: monitoring and management, NICE, 2023. https://www.nice.org.uk/guidance/ng231
  7. Diagnosis and management of Barrett esophagus: European Society of Gastrointestinal Endoscopy (ESGE) Guideline, 2023. https://www.bsg.org.uk/getmedia/88cfdd3f-2593-4cd5-bb9a-ff1c1d4e0c61/ESGE-Barretts-Guideline.pdf?ext=.pdf
  8. Chien S, et al. Oesophageal cell collection device and biomarker testing to identify high-risk Barrett's patients requiring endoscopic investigation. Br J Surg. 2024 May 3;111(5):znae117.
  9. Chien S, et al. CytoSCOT group. National adoption of an esophageal cell collection device for Barrett's esophagus surveillance: impact on delay to investigation and pathological findings. Dis Esophagus. 2024 Apr 27;37(5):doae002.
  10. Bouzid K, et al. Enabling large-scale screening of Barrett’s esophagus using weakly supervised deep learning in histopathology. Nature Communications [Internet]. 2024 Mar 11 [cited 2024 Mar 21];15:2026.
  11. Gehrung M, et al. Triage-driven diagnosis of Barrett’s esophagus for early detection of esophageal adenocarcinoma using deep learning. Nat Med 27, 833–841 (2021).
  12. Pilonis ND, et al. 2022 Use of a Cytosponge biomarker panel to prioritise endoscopic Barrett's oesophagus surveillance: a cross-sectional study followed by a real-world prospective pilot Lancet Oncoloy Vol:23: 2, p270-278
  13. Berman, A.G., et al. (2022). Quantification of TFF3 expression from a non-endoscopic device predicts clinically relevant Barrett’s oesophagus by machine learning. eBioMedicine, 82, p.104160.