Refining esophageal cancer staging after neoadjuvant therapy: Importance of treatment response

Objective: Accurate staging is vital for esophageal cancer management. The utility of the American Joint Committee on Cancer (AJCC) staging system 6th edition for esophageal cancer has been questioned for resected patients who receive neoadjuvant chemoradiotherapy (CRT). This study was undertaken to assess the AJCC staging system for patients with esophageal cancer that have received neoadjuvant CRT and to identify clinicopathological variables that predict survival. Methods: Review of a prospective esophageal cancer database was undertaken for patients that received neoadjuvant CRT and resection. Primary tumor response was defined as major (>10% residual tumor cells) or minor (> 10% residual tumor cells). Cox regression and concordance analyses were used to determine prognostic factors. Median follow-up was 61 months. Results: Of 131 patients with invasive cancer, there were 40/131 (31%) with squamous cell carcinoma (SCC) and 88/131 (65%) with adenocarcinoma. The procedure-related mortality rate was 3.8%. Median survival was 33 months. A major response was demonstrated by 79/131 (60%) patients. Survival analyses found that the AJCC 6th edition was unable to discriminate between stages 0, I, and IIa or stages IIb and III. Multivariate survival analyses found age, pretreatment tumor length > 6 cm, positive lymph nodes, and a major tumor response were independent prognostic factors. These data were used to derive a new staging system that had improved discrimination of stage groups over the current AJCC system. Conclusion: The current AJCC staging system for esophageal cancer is inadequate for patients that receive neoadjuvant CRT. Refinement of the AJCC staging system should include primary tumor response for patients receiving neoadjuvant CRT.