Endoscopic resection (ER) is the recommended treatment for superficial visible lesions in patients with a Barrett esophagus (BE). Following non-curative endoscopic therapy for BE-related dysplasia or esophageal adenocarcinoma (EAC), or in case of a local recurrence at the ER scar for which additional ER is not deemed feasible, step-up treatment with esophagectomy and/or chemo/radiotherapy is typically considered. However, step-up treatment may not always be possible due to comorbidities and/or age or may be declined based on patient preference. This case series evaluates the use of endoscopic focal cryoballoon ablation (CBA) as potential alternative therapy.

This retrospective case series was conducted at two Dutch tertiary referral centers. Patients with BE-related dysplasia or EAC were included if they underwent focal CBA between January 2018 and July 2025 for two indications: 1) prophylactic therapy following non-curative endoscopic treatment defined as a macroscopically incomplete ER, or an ER with vertical tumor-positive resection margins (R1v), and 2) an endoscopically visible neoplastic lesion <1 cm from the ER scar for which additional ER was not deemed feasible. Treatment was performed using either the first- or second-generation CBA device, with an ablation dose of 10 to 12 seconds. The number of ablations and freeze–thaw cycles was determined at the discretion of the endoscopist. Outcomes were technical success, safety, endoscopic remission — defined as the absence of any endoscopically visible lesions suspected of dysplasia or cancer during endoscopic follow-up — and survival.

In total, 11 patients underwent focal CBA after a non-curative ER or an endoscopically visible lesion <1cm from the resection scar. Patients had a median age of 77 years (p25-p75 68-81) at time of treatment, and the majority was male (9/11; 82%). Reasons for not undergoing additional treatment with esophagectomy and/or chemo/radiotherapy included severe comorbidity and/or advanced age (n=5) and patient preference (n=6).

Seven patients (7/11; 64%) underwent prophylactic CBA following non-curative endoscopic treatment, and four patients (4/11; 36%) had treatment for an endoscopically visible lesion <1cm from the ER scar. CBA was technically feasible in all cases, and no (serious) adverse events occurred.

In patients who underwent prophylactic CBA after non-curative endoscopic therapy, endoscopic remission was retained in 71% of patients (5/7) and this sustained during a median endoscopic follow-up of 14 months (range 3-51) with median 2 endoscopies (range 1-3). Among patients with a local recurrence at the resection scar, 50% (2/4) achieved endoscopic remission and this sustained during a median endoscopic follow-up of 7 months (range 6–8) with median 6 endoscopies (range 2-10).

Overall, 45% of patients (5/11) died median 26 months (range 12-36) after CBA. Three of these deaths were attributable to esophageal cancer, and were all in patients who did not achieve endoscopic remission. 

In expert hands, focal CBA is feasible and safe following non-curative endoscopic therapy for BE-related dysplasia or EAC and for local recurrences in the ER scar. However, efficacy is limited, and therefore CBA should not be regarded as reliable alternative to esophagectomy and/or chemo/radiotherapy.