P84 LOCALIZATION OF UNDETECTED RESIDUAL TUMOR AFTER NEOADJUVANT CHEMORADIOTHERAPY IN PATIENTS WITH ESOPHAGEAL CANCER

Introduction The preSANO-trial aimed to determine accuracy of clinical response evaluations (CREs) after neoadjuvant chemoradiotherapy (nCRT) in patients with locally-advanced esophageal cancer. After introduction of the ‘bite-on-bite’ biopsy-technique, most residual tumors were detected. Aim of this study was to determine the location of residual tumors that were not detected during CREs and whether or not endoscopic (bite-on-bite) biopsies had the theoretical potential to detect these tumors. Methods In this side-study of the prospective preSANO trial, biopsies and resection specimens were independently revised by two GI-pathologists. All patients were included that had residual tumor in the resection specimen that was not detected during two clinical response evaluations, 6 and 12 weeks after completion of nCRT. In the resection specimen, the tumor regression grade was defined for each esophageal wall layer. It was determined how often submucosal tumors under a tumor-free mucosal layer were missed during CREs. Biopsies taken during CREs were revised for the presence of submucosal tissue. This was defined as presence of submucosal structures, i.e. submucosal glands and/or thick-walled vessel-structures. Results Some 103 of 207 patients underwent CREs followed by surgery. Residual tumor was not detected during CREs in 33 patients. Resection specimens of 28 of these patients were available for revision. Missed residual tumors were located in the mucosal layer of the esophageal wall in 64% of these patients. Residual tumors were located in the submucosal layer, under a tumor-free mucosal layer, in 29% of patients. One patient still had tumor under a tumor-free mucosal- and submucosal layer. Submucosal structures were detected in two patients and it was uncertain whether submucosal tissue was present in six patients, while no specific submucosal structures were detected in 21 patients. Conclusion The majority of patients in whom residual tumor remained undetected during clinical response evaluations had tumor cells in the mucosal layer of the esophageal wall. Nearly one third of the patients had tumor in the submucosal layer under a tumor-free mucosa. Whether these submucosal tumors can be detected using endoscopic biopsies is uncertain. Further improvement of the accuracy of CREs should focus on sampling of larger mucosal areas, for example by using brush techniques.