LAUSR

OBJECTIVE We conducted a prospective trial (NCT01393483) to investigate the utility of serum soluble mesothelin related peptide (SMRP) and tumor mesothelin expression in the management of esophageal adenocarcinoma (ADC). SUMMARY BACKGROUND DATA 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 prior to induction chemoradiation (pre-treatment) and at the time of resection (post-treatment), as a biomarker for treatment response, disease recurrence and overall survival (OS). RESULTS Pre- and post-treatment 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. Pre-treatment 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). Pre-treatment tumor mesothelin expression was associated with OS (HR, 2.08; 95% CI, 1.14-3.79; P=0.017) but had no statistically significant association with recurrence (P=0.9). 3-year OS of patients with pre-treatment tumor mesothelin expression of ≤25% was 78% (95% CI, 68-89%), compared to 49% (95% CI, 35-70%) among those with >25%. CONCLUSIONS Pre-treatment 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.