Persistence of Lugol-unstaining is associated with an increased risk of progression to malignancy in the esophagus.

Background and aims: To investigate the persistence of Lugol-unstained lesions (LULs) in the esophagus detected by chromoendoscopy and explore its association with progression to malignancy.

Methods: We enrolled 647 participants from a population-based screening trial who had biopsied LULs at the baseline chromoendoscopy and underwent a chromoendoscopy reexamination after a median of 4.39 years. Cases of persistent LUL were defined as those in whom a visible LUL was observed during reexamination at the documented location (±2cm) where a LUL was detected at baseline chromoendoscopy. Logistic regression was applied to explore risk factors for the persistence of LULs. The primary outcome was clinical-stage esophageal squamous cell carcinoma (ESCC) identified over 6.78 years of follow-up and the secondary outcome was reexamination-detected severe dysplasia and above lesions (SDA). The cumulative incidence was calculated to assess the progression risk associated with the persistence of LULs.

Results: The proportion of participants with persistent LULs was 81.92%. Dysplasia (adjusted OR=6.16, 95%CI: 2.70 to 17.80), large LULs (adjusted OR=1.90, 95%CI: 1.18 to 3.15), and irregularly shaped LULs (adjusted OR=1.63, 95%CI: 1.03 to 2.56) at baseline were associated with an increased risk of LUL persistence. Eleven clinical-stage ESCC cases and 31 SDAs detected during reexamination were identified, all of which originated from patients with persistent LULs (P_{clinical-stageESCC} =0.136, P_{reexamination-detected SDA} =0.015).

Conclusion: The persistence of LULs is associated with progression to malignancy in the esophagus, even in individuals without dysplastic lesions. Based on this, a more efficient post-screening surveillance strategy could be established.