{
  "abstract": "Introduction Diagnosis of symptomatic oesophageal adenocarcinoma (OAC) leads to poor survival and morbid treatments. Identifying individuals with the precursor condition Barrett’s oesophagus (BO) enables early detection of dysplasia and stage 1 cancer, when endoscopic therapy is most effective. The BO Screening Trial 3 (BEST3), a randomized controlled trial, demonstrated that the capsule-sponge-trefoil-factor-3 (CS-TFF3) test increased BO detection by 10-fold compared with usual care and enabled diagnosis of dysplasia and early cancer. The aim of this study was to determine the long-term risk of missed OAC or gastric cancers among BEST3 participants who swallowed the capsule sponge and had a negative test.Methods Participants in BEST3 ( ISRCTN68382401), aged >50 years with a history of heartburn, were referred for endoscopy if their capsule sponge sample was TFF3 positive or demonstrated cellular atypia. In addition, 4.1% of patients with a negative CS-TFF3 test also underwent endoscopy as a random control sample. We obtained cancer incidence and mortality data up to June 2025 from the UK Cancer Registry and Civil Registration Mortality datasets for BEST3 participants who underwent the CS-TFF3 test. Linkage was achieved for 94% (1,651/1,750) of participants of which 97.6% (1,611/1,651) completed the CS-TFF3 test. We assessed long-term outcomes for these individuals, particularly assessing for any newly diagnosed OAC or gastric cancers that may have been missed by the original CS-TFF3 test.Results During the initial BEST3 analysis period (1-year post-enrolment), the CS-TFF3 pathway correctly detected 3 OACs, 3 cases of BO with high-grade dysplasia, and 1 gastric cancer ( figure 1). In our extended follow-up (median 6.9 years (IQR 6.4–7.3)), no additional OACs were identified among 1,370 participants who previously tested negative/equivocal on the CS-TFF3 test. One participant was diagnosed with a gastric cardia cancer five years after a negative test. Overall, the negative predictive value of the CS-TFF3 test for dysplasia/cancer was 99.9% (95% CI: 99.5 – 100%).Conclusions Long-term registry follow-up data of the BEST3 cohort demonstrate that the CS-TFF3 screening approach is not associated with missed OAC. Even when including gastric cancers, at median follow-up of almost 7 years, the missed cancer rate for a negative test is 0.07%. These findings support the safety, reliability, and clinical utility of the CS-TFF3 test as a non-endoscopic screening strategy for BO in high-risk populations.Abstract O70 Figure 1Flow of CS-TFF3 results and cancer outcomes in the BEST3 cohort. Altogether, 9/241 (3.7%) of patients who were positive for TFF3, atypia or both on capsule sponge had a diagnosis of BO with high-grade dysplasia or worse, compared to 1/1370 (0.07%) in the TFF3 negative/equivocal group",
  "authors": [
    {
      "affiliations": [
        "Early Cancer Institute, Department of Oncology, University of Cambridge, Cambridge, United Kingdom"
      ],
      "name": "Caryn Ross-Innes"
    },
    {
      "affiliations": [
        "Early Cancer Institute, Department of Oncology, University of Cambridge, Cambridge, United Kingdom"
      ],
      "name": "Timothy Somerset"
    },
    {
      "affiliations": [
        "Early Cancer Institute, Department of Oncology, University of Cambridge, Cambridge, United Kingdom",
        "Department of Gastroenterology, Addenbrookes Hospital, Cambridge University NHS Foundation Trust, Cambridge, United Kingdom"
      ],
      "name": "Andreas Hadjinicolaou"
    },
    {
      "affiliations": [
        "Early Cancer Institute, Department of Oncology, University of Cambridge, Cambridge, United Kingdom"
      ],
      "name": "Anne Babbage"
    },
    {
      "affiliations": [
        "Early Cancer Institute, Department of Oncology, University of Cambridge, Cambridge, United Kingdom"
      ],
      "name": "Adam Freeman"
    },
    {
      "affiliations": [
        "Early Cancer Institute, Department of Oncology, University of Cambridge, Cambridge, United Kingdom",
        "Department of Gastroenterology, Addenbrookes Hospital, Cambridge University NHS Foundation Trust, Cambridge, United Kingdom"
      ],
      "name": "Rebecca Fitzgerald"
    }
  ],
  "title": "O70 Long term follow-up from the barrett’s oesophagus screening trial 3 (BEST3) demonstrates the safety of capsule-sponge-trefoil-factor-3 test for barrett’s oesophagus",
  "uid": "cc3782f7-d793-5c59-bd4e-df1e9ca277b9"
}