An experimental cell-collection device that can be administered without anesthesia in a primary care practice was shown to be better at detecting Barrett esophagus than the standard of care in a community-based clinical trial.
Use of this patient-swallowed device, called Cytosponge-TFF3, could allow clinicians to diagnose esophageal conditions such as dysplasia or cancer at an earlier and potentially curable stage, say the investigators. However, it would also increase the likelihood of unnecessary endoscopies, owing to false positive results, they note.
"In this multicenter, pragmatic, randomized controlled trial we found that an invitation to have a Cytosponge-TFF3 test led to increased diagnosis of Barrett's esophagus when compared with usual care by general practitioners," write Rebecca C. Fitzgerald, MD, from the Hutchison/MRC Research Center in Cambridge, United Kingdom, and colleagues.
The study was published online on August 1 in The Lancet.
"This is a very important study, a landmark study," said Stephen J. Meltzer, MD, professor of medicine and oncology at Johns Hopkins University in Baltimore, Maryland, who was approached for comment.
"What it shows is that if you opt to have this procedure, you're much more likely to have your Barrett's diagnosed than if you don't opt to have it," he said.
He congratulated Fitzgerald and colleagues for successful completion of a large, primary practice–based clinical utility study.
"Those studies are very difficult to do. This is looking at the actual impact of an intervention, which is the sponge," he said in an interview with Medscape Medical News.
Soaking Up Cells
Meltzer was senior author of a case-control study published in 2019 in Clinical Cancer Research that described use of a similar device. As previously reported, that device, called EsophaCap, uses a "methylation on bead" technique to collect DNA on a swallowed sponge. The DNA is then extracted from the sponge and analyzed with a methylation biomarker panel.
Like the EsophaCap device, the Cytosponge-TFF3 device consists of a compressed, gelatin-coated collection sponge attached to a thread. The patient swallows the device. After the gelatin dissolves and the sponge expands, it is gently withdrawn through the esophagus, picking up cells as it passes through.
The collected cells are then analyzed with an in vitro test for biomarker trefoil factor 3 (TFF3), a sign of intestinal metaplasia that is a histopathologic hallmark of Barrett esophagus, the authors explain.
The study by Fitzgerald and colleagues was conducted in patients taking medications for gastroesophageal reflux. The patients were undergoing treatment at 109 general practice clinics in England.
Eligible patients included adults aged 50 years and older who had been taking acid-suppressing medication for gastroesophageal reflux for more than 6 months and had not undergone endoscopy within the previous 5 years.
The study was randomized at both the clinic level (cluster randomization) and the individual patient level. Patients were assigned to either standard management of gastroesophageal reflux, with endoscopies performed only if recommended by the practitioner, or to the intervention group, where individuals received usual care and were offered the Cytosponge-TFF3 procedure. Those patients whose samples yielded TFF3-positive cells subsequently underwent endoscopy.
Among 6834 patients assigned to the intervention group, 2679 (39%) expressed willingness to undergo the Cytosponge-TFF3 procedure. Of this group, 1750 patients met all of the eligibility criteria on telephone screening and underwent the procedure.
The large majority of patients (95%) who agreed to undergo the procedure were able to swallow the capsule and the attached thread.
Patients in the intervention group who declined the Cytosponge-TFF3 and all patients assigned to the usual-care arm underwent endoscopy only at the recommendation of their primary practitioner.
During a mean follow-up of 12 months, 140 of the 6834 patients in the intervention group (2%) were diagnosed with Barrett esophagus, compared with 13 of 6388 patients in the usual-care group (0.2%). The absolute difference per 1000 person-years, the trial's primary endpoint, was 18.3. The rate ratio adjusted for cluster randomization was 10.6 (P
A total of four patients in the intervention group were diagnosed with dysplastic Barrett esophagus, and five were diagnosed with stage I esophagogastric cancer. No patients in the usual-care group were diagnosed with either condition.
Of the 1654 patients in the intervention group who opted for the Cytosponge device and swallowed it successfully, 221 underwent endoscopy after testing positive for TFF3. Of these patients, 131 (59%) were diagnosed with either Barrett esophagus or cancer.
The most common adverse event with the Cytosponge procedure was sore throat, reported by 4% of those who opted for it. In one patient, the thread became detach from the Cytopsonge, necessitating endoscopy to remove the device.
In an editorial accompanying the study, Yuri Hanada, MD, and Kenneth K. Wang, MD, from the Department of Gastroenterology at the Mayo Clinic in Rochester, Minnesota, say that the Cytosponge-TFF3 procedure "is a promising non-endoscopic screening tool and will represent a component in the screening for Barrett's esophagus and esophago-gastric cancer."
They note, however, that it is unlikely to be the sole screening tool for Barrett esophagus and that its use in primary practice may be problematic during the COVID-19 pandemic, because of the release of aerosolized particles as the sponge is withdrawn from the esophagus.
"It might also be necessary to enrich disease prevalence in the screened population by limiting this population to males and people with other risk factors, in order to make this test more cost-effective than previously shown," they wrote.
Meltzer noted that despite being less invasive than endoscopy, only 39% of the group who could try it agreed to do so.
"It was kind of surprising, because in my experience, when I offer it to my patients, the acceptance is much higher, but that's not in a controlled clinical trial situation, so I don't really know what the true percentage is," he said.
He pointed out that the patients he sees in his clinic are more likely to be symptomatic and highly motivated to accept a test, in contrast to the general patient population in the study.
He also noted that the endoscopy-confirmed prevalence rate of Barrett esophagus or cancer in 221 patients in the intervention group was 59%, suggesting that 41% underwent an unnecessary endoscopy after the Cytosponge screening.
Fitzgerald and colleagues acknowledge the potential for overdiagnosis with screening. They note a debate as to whether 1 cm or short segments of Barrett esophagus are a cause for clinical concern.
They also note that the TFF3 test (used in the CytoSponge device) is sensitive and detects some short segments of Barrett esophagus and that "since this was a pragmatic trial that relied on a coded diagnosis of Barrett's esophagus, we also identified patients in the usual care group who had short segments of Barrett's esophagus (1 cm or less in length) and were diagnosed as having the condition, reflecting the variable practice in UK hospitals.
"We expect that these patients can be reassured and probably do not require surveillance," they continue. "This expectation is consistent with the clinical guidelines, which suggest that patients with over 1 cm of salmon-colored epithelium containing intestinal metaplasia should be monitored."
The study was funded by Cancer Research UK, the UK National Institute for Health Research, the UK National Health Service, Medtronic, and the Medical Research Council. Fitzgerald is named on patents related to the Cytosponge-TFF3 test. Meltzer has co-founded a company, Capsulomics, to commercialize the methylation biomarker panel used in EsophaCap studies. Wang has received research funding from eNose for research on a device used in a screening study of Barrett esophagus.
The article was originally published on Medscape.com.