Serum Soluble Mesothelin Concentrations in Malignant Pleural Mesothelioma: Relationship to Tumor Volume, Clinical Stage and Changes in Tumor Burden

Purpose: To examine the clinical utility of soluble mesothelin in patients with malignant pleural mesothelioma. Experimental Design: A total of 97 patients (female: 11; male: 86) were prospectively enrolled, longitudinal serum samples collected, and mesothelin concentrations determined. Baseline mesothelin levels were analyzed relative to tumor stage, presence of metastatic disease, the positron emission tomography (PET) parameters maximum standardized uptake value, tumor volume, total glycolytic volume, and survival. Changes in mesothelin level were correlated to objective response to chemotherapy, as assessed radiologically and by PET imaging, and with patient survival. Results: Baseline mesothelin levels greater than 5 nmol/L were a significant negative prognostic indicator (HR = 2.25; 95% CI, 1.20-4.21) and correlated with tumor stage and volume. In 55 patients who received chemotherapy, change in mesothelin correlated with radiological response (chi(2) = 11.32; P = 0.023) and change in metabolically active tumor volume (r = 0.58; P < 0.01). Median survival for patients with a reduction in mesothelin following chemotherapy (19 months) was significantly longer than for patients with increased mesothelin (5 months; P < 0.001). Conclusion: These findings show the potential value of changes in mesothelin levels for prognostication and monitoring of treatment response in mesothelioma. Clin Cancer Res; 17(5); 1181-9. (C)2010 AACR.