THE TISSUE SYSTEMS PATHOLOGY TEST ENABLES RISK-ALIGNED MANAGEMENT FOR PATIENTS WITH BARRETT’S ESOPHAGUS

Introduction: The goal of Barrett’s esophagus (BE) surveillance is to detect dysplasia and esophageal adenocarcinoma (EAC) at early, treatable stages. Effective endoscopic eradication therapy (EET) is available; however, it is challenging to identify which patients will benefit from EET, particularly in patients with non-dysplastic BE (NDBE). The uncertainty about risk has led to overuse of endoscopy and EET in NDBE. Early detection of NDBE patients who are at high risk for progression to high-grade dysplasia (HGD)/EAC is essential for improving patient health outcomes. This study evaluated the clinical utility of the tissue systems pathology test (TissueCypher, TSP-9) test to escalate care to short-interval surveillance or EET in NDBE patients who are at high risk for progression in a diverse cohort of patients with known clinical outcomes.
Methods: 699 BE patients with known progression outcomes were evaluated, of which 392 had an original diagnosis of NDBE, 63 had IND, and 244 had LGD. 190 patients were diagnosed with HGD/EAC a median 2.6 (IQR 1.2-4.2) years later, and 509 did not progress during median 6.7 (IQR 5-9) years follow-up. Management decisions were simulated for patients using the pathology diagnosis per guidelines (Fig 1A.1), real-world practice with overuse of care (30% NDBE patients underwent surveillance prior to 3 years and 0.5% received EET, Fig 1A.2), or TSP-9 results to determine the care plan (Fig. 1A.3). Management decisions were scored as appropriate or not appropriate per the known clinical outcomes as detailed in Fig. 1B.
Results: Use of TSP-9 significantly increased the percentage of BE patients receiving appropriate management from 67.4% (95% CI 64–71) for guideline-directed care, or 59.8% (95% CI 56-63) for real-world care, to 75.3% (95% CI 72–78) (P=0.005 and P<0.0001, respectively, Fig. 2A). Use of TSP-9 led to a 49% decrease in undertreatment of progressors (P<0.0001) without significantly increasing overtreatment of non-progressors versus guideline-directed care (Fig. 2B and 2C). TSP-9 also significantly reduced overuse of endoscopy and EET in non-progressors versus real-world care (Fig. 2C). The highest overall utility of TSP-9 was observed in NDBE where use of TSP-9 results significantly increased the percentage of patients who progressed to HGD/EAC receiving short-interval surveillance or EET to 56.9% (95% CI 47–67) from 30.4% (95% CI 22-40) when compared to real-world care (P=0.001) and from zero when compared to guideline-directed care (P<0.0001) (Fig. 2E).
Conclusions: Use of TSP-9 demonstrated significant clinical utility in patients with NDBE who progressed to HGD/EAC, enabling significantly more progressors to be managed with short-interval surveillance or EET to prevent progression. Guidance from TSP-9 can enable risk-aligned care for NDBE patients in a manner consistent with improved health outcomes.