Apoptosis in esophageal cancer following induction chemoradiotherapy

The poor survival of patients with esophageal cancer following esophagectomy has led to intense investigation into combined modality therapy. Based on results from clinical trials examining chemoradiotherapy alone without surgery, resection has come under increased scrutiny and its necessity as a component of a multimodal approach has been questioned. In this study, we examined whether residual tumor cells in esophagectomy specimens following induction chemoradiotherapy are viable and, therefore, provide putative evidence for the appropriateness of esophagectomy.

Between August 1991 and January 1995, 46 patients were entered into an induction chemoradiotherapy trial consisting of 5-fluorouracil, cisplatin, alpha-interferon, and concurrent external beam radiotherapy followed by esophagectomy. Response was determined histologically and apoptosis assessed with a terminal deoxytransferase assay system. p53 status was determined by immunohistochemistry and mutational analysis.

Thirty-eight patients underwent esophagectomy, 33 of whom had either a complete (n = 10) or partial (n = 23) response. None of the 28 patients with residual tumor in the resected specimen had 100% apoptotic cells and the vast majority of specimens had less than a 10% apoptotic rate. The percentage of apoptotic cells did correlate with tumor differentiation but not with histologic type nor presence of p53 mutations.

These data suggest that resection following upfront chemoradiotherapy is a necessary component of a multimodality approach to esophageal cancer and will ultimately provide superior local-regional control to a nonsurgical approach.