Use of bone marrow micrometastasis to predict disease-free and overall survival in esophageal cancer: Evaluation of 304 cases

Abstract

4519 Background: The presence of bone marrow micrometastases (BMM) yields prognostic information for patients at higher risk for recurrence and death. Aim of the study was to evaluate the role of BMM in esophageal cancer (EC). Methods: 304 consecutive patients operated for EC and with BMM status were included into the prospective study. BMM were assessed by a pan-anti- cytokeratin monoclonal antibody, A45-B/B3. Associations between BMM status and clinicopathological parameters as well as disease-free (DFS) and overall survival (OS) were calculated with chi-square-, log-rank test and Cox multivariate analysis. Results: Out of 304 patients 109 (35.9%) were BMM positive (BMM+) and 195 (64.1%) negative (BMM-). Significant correlation was found between BMM and tumor size, nodal stage and recurrence (P=0.02, 0.002 and <0.0001). DFS and OS were significantly better in BMM- compared to BMM+ patients (median 44.2 and 31.6 vs. 10.4 and 12.4 months, P<0.0001). Sub-analyses revealed that nodal negative (N-) patients with BMM- had a significant better DFS and OS compared to N- and BMM+ patients (50.8 and 41.5 vs. 18.0 and 16.3 months, P<0.0001). Nodal positive patients (N+) with BMM- had a better DFS and OS compared to N+ and BMM+ patients (22.1 and 24.8 vs. 9.0 and 11.3 months, P<0.0001). In the Cox multivariate analysis BMM was the strongest predictor of DFS and OS with a hazard ratio of 3.1 and 2.9 (P<0.0001). Also tumor size and nodal stage were found to be significant predictors, whereas age and sex were not. All analyses were repeated after stratification of the study group to underlying tumor type (adenocarcinoma (AC) and squamous cell carcinoma (SCC)). Significant differences were found at all levels as reported for the entire study group above within the AC and SCC group as well. Conclusions: To our knowledge this is the largest study evaluating the role of BMM in EC. Survival sub-analyses stratified to nodal and bone marrow status revealed a significant role of BMM in EC. Presence of BMM proved to be the strongest predictor of DFS and OS in AC and SCC of the esophageus. No significant financial relationships to disclose.