Esophageal cancer recurrence after multimodality therapy: analysis of patterns and implications on long-term survival

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Background: Many patients with esophageal cancer experience recurrence after curative-intent multimodality therapy. This study aims to evaluate risk factors, patterns, and outcomes of esophageal cancer recurrence after neoadjuvant chemoradiotherapy and esophagectomy. Methods: Single-institution retrospective review of patients who underwent multimodality therapy including esophagectomy for esophageal adenocarcinoma or squamous cell carcinoma (SCC) from 2011 to 2021. Detailed data on recurrence patterns was collected. Factors associated with time to recurrence, overall survival, and survival after recurrence were analyzed. Results: There were 665 patients included of which 627 (94%) had clinical stage ≥ II disease. Recurrence after esophagectomy occurred in 241 (36%) patients. Median time to recurrence was 9.9 months (interquartile range, 5.4-18.8 months). Recurrence was distant in 119 (49%) patients, regional in 72 (30%) patients, local in 12 (5%), locoregional in 2 (0.8%), and locoregional + distant in 35 (15%). Factors independently associated with a higher risk of recurrence included male sex, SCC histology, and pN stage. Downstaging after neoadjuvant therapy was associated with a lower risk of recurrence. Recurrence was associated with a higher risk of death (adjusted hazard ratio 5.95, 95% confidence interval: 4.73-7.50, P<0.001). Median overall survival after surgery was 12 months in patients with recurrence and 123 months in patients without recurrence. Recurrences in the pleura and bone were independently associated with decreased post-recurrence survival. Conclusions: The incidence of recurrence, particularly distant, remains high despite neoadjuvant therapy and esophagectomy, consistent with observations from clinical trials. Better perioperative systemic therapies are needed for patients with locally advanced esophageal cancer.

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