A Prospective Clinical Trial to Evaluate Mesothelin as a Biomarker for the Clinical Management of Patients with Esophageal Adenocarcinoma

Abstract

Objective: To investigate the utility of serum soluble mesothelin-related peptide (SMRP) and tumor mesothelin expression in the management of esophageal adenocarcinoma (ADC). Background: Clinical management of esophageal ADC is limited by a lack of accurate evaluation of tumor burden, treatment response, and disease recurrence. Our retrospective data showed that tumor mesothelin and its serum correlate, SMRP, are overexpressed and associated with poor outcomes in patients with esophageal ADC. Methods: Serum SMRP and tumoral mesothelin expression from 101 patients with locally advanced esophageal ADC were analyzed before induction chemoradiation (pretreatment) and at the time of resection (posttreatment), as a biomarker for treatment response, disease recurrence, and overall survival (OS). Results: Pre and posttreatment serum SMRP was ≥ 1 nM in 49% and 53%, and pre and post-treatment tumor mesothelin expression was > 25% in 35% and 46% of patients, respectively. Pretreatment serum SMRP was not significantly associated with tumor stage (P = 0.9), treatment response (radiologic response, P = 0.4; pathologic response, P = 0.7), or recurrence (P = 0.229). Pretreatment tumor mesothelin expression was associated with OS (hazard ratio: 2.08; 95% CI: 1.14-3.79; P = 0.017) but had no statistically significant association with recurrence (P = 0.9). Three-year OS of patients with pretreatment tumor mesothelin expression of ≤ 25% was 78% (95% CI: 68%-89%), compared with 49% (95% CI: 35%-70%) among those with > 25%. Conclusions: Pretreatment tumor mesothelin expression is prognostic of OS for patients with locally advanced esophageal ADC, whereas serum SMRP is not a reliable biomarker for monitoring treatment response or recurrence.